WorldWideScience

Sample records for bacterial vaccine safety

  1. Vaccine Safety

    Science.gov (United States)

    ... Tweet Share Compartir Back to School: Vaccines for Preteens Learn about the safety of Tdap, Meningococcal, and ... file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file ...

  2. Vaccine Safety Datalink

    Science.gov (United States)

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  3. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    Science.gov (United States)

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

  4. Ensuring safety of DNA vaccines

    Directory of Open Access Journals (Sweden)

    Wessels Stephen

    2005-09-01

    Full Text Available Abstract In 1990 a new approach for vaccination was invented involving injection of plasmid DNA in vivo, which elicits an immune response to the encoded protein. DNA vaccination can overcome most disadvantages of conventional vaccine strategies and has potential for vaccines of the future. However, today 15 years on, a commercial product still has not reached the market. One possible explanation could be the technique's failure to induce an efficient immune response in humans, but safety may also be a fundamental issue. This review focuses on the safety of the genetic elements of DNA vaccines and on the safety of the microbial host for the production of plasmid DNA. We also propose candidates for the vaccine's genetic elements and for its microbial production host that can heighten the vaccine's safety and facilitate its entry to the market.

  5. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  6. Live bacterial vaccine vectors: An overview

    Directory of Open Access Journals (Sweden)

    Adilson José da Silva

    2014-12-01

    Full Text Available Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.

  7. Bacterial vaccines and antibiotic resistance

    OpenAIRE

    Henriques-Normark, Birgitta; Normark, Staffan

    2014-01-01

    Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to gene...

  8. Vaccination against bacterial kidney disease: Chapter 22

    Science.gov (United States)

    Elliott, Diane G.; Wiens, Gregory D.; Hammell, K. Larry; Rhodes, Linda D.; Edited by Gudding, Roar; Lillehaug, Atle; Evensen, Øystein

    2014-01-01

    Bacterial kidney disease (BKD) of salmonid fishes, caused by Renibacterium salmoninarum, has been recognized as a serious disease in salmonid fishes since the 1930s. This chapter discusses the occurrence and significance, etiology, and pathogenesis of BKD. It then describes the different vaccination procedures and the effects and side-effects of vaccination. Despite years of research, however, only a single vaccine has been licensed for prevention of BKD, and has demonstrated variable efficacy. Therefore, in addition to a presentation of the current status of BKD vaccination, a discussion of potential future directions for BKD vaccine development is included in the chapter. This discussion is focused on the unique characteristics of R. salmoninarum and its biology, as well as aspects of the salmonid immune system that might be explored specifically to develop more effective vaccines for BKD prevention.

  9. Vaccine safety controversies and the future of vaccination programs.

    Science.gov (United States)

    François, Guido; Duclos, Philippe; Margolis, Harold; Lavanchy, Daniel; Siegrist, Claire-Anne; Meheus, André; Lambert, Paul-Henri; Emiroğlu, Nedret; Badur, Selim; Van Damme, Pierre

    2005-11-01

    In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

  10. Russian vaccines against especially dangerous bacterial pathogens

    Science.gov (United States)

    Feodorova, Valentina A; Sayapina, Lidiya V; Corbel, Michael J; Motin, Vladimir L

    2014-01-01

    In response to the epidemiological situation, live attenuated or killed vaccines against anthrax, brucellosis, cholera, glanders, plague and tularemia were developed and used for immunization of at-risk populations in the Former Soviet Union. Certain of these vaccines have been updated and currently they are used on a selective basis, mainly for high risk occupations, in the Russian Federation. Except for anthrax and cholera these vaccines currently are the only licensed products available for protection against the most dangerous bacterial pathogens. Development of improved formulations and new products is ongoing. PMID:26038506

  11. A NEW APPROACH TO BACTERIAL VACCINES.

    Science.gov (United States)

    GREENBERG, L

    1963-08-31

    Immunizing antigens against only 10 bacterial diseases-cholera, diphtheria, paratyphoid, pertussis, plague, scarlet fever, staphylococcal disease, tetanus, tuberculosis and typhoid-have been licensed for sale in Canada and the United States. Convincing evidence of efficacy is available for only four of these-diphtheria and tetanus toxoids, and pertussis and typhoid vaccines.The principles which determine the efficacy of different immunizing antigens are not always the same. Toxoids, for example, stimulate the formation of antitoxin-producing mechanisms which can neutralize toxins produced by invading organisms, thereby rendering them harmless. Conversely, vaccines stimulate the formation of antibacterial mechanisms which stop the growth of organisms before they can produce disease.Use of enzyme-lysed vaccines for prevention of staphylococcal disease represents a new approach in vaccine research. Animal tests have shown lysed vaccines to be 10 to 100 times less toxic, and about eight times more effective, than whole bacterial vaccines. Studies with lysed vaccines for other diseases are now in progress.

  12. Communicating vaccine safety during the development and introduction of vaccines.

    Science.gov (United States)

    Kochhar, Sonali

    2015-01-01

    Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.

  13. Meningococcal Disease (Bacterial Meningitis) Vaccine and Pregnancy

    Science.gov (United States)

    Meningococcal Disease (Bacterial meningitis) Vaccine and Pregnancy In every pregnancy, a woman starts out with a 3-5% chance of having a baby ... advice from your health care provider. What is meningitis? Meningitis is an infection of the lining that ...

  14. Bacterial otitis media: current vaccine development strategies.

    Science.gov (United States)

    Cripps, Allan W; Kyd, Jennelle

    2003-02-01

    Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.

  15. Live bacterial vaccines – a review and identification of potential hazards

    Directory of Open Access Journals (Sweden)

    Detmer Ann

    2006-06-01

    Full Text Available Abstract The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.

  16. [Vaccination safety and media publicity strategy].

    Science.gov (United States)

    Tan, Jibin; Guo, Xiaomin; Li, Keli; Zhang, Xiumin

    2016-03-01

    Due to the over negative report of adverse event following immunization (AEFI) by media, some people began to question the safety of vaccination. Date published since 2005 were collected by literature retrieval, mainly including relative AEFI date, current status of media report of AEFI, public awareness about AEFI. Public concern about the vaccination safety mainly focused on the serious diseases which might be caused, influence on immune system. Media' s over negative reactions to AEFI and lack of related knowledge in general public have led to the public' s concern about vaccination safety. Vaccination is the most economical and effective measure for the prevention of diseases and AEFI incidence rate is very low. Therefore, it is necessary for media to give more positive report about vaccination safety.

  17. Seasonal Flu Vaccine Safety and Pregnant Women

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  18. The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

    Science.gov (United States)

    Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

    2015-12-30

    Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children.

  19. A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

    Science.gov (United States)

    García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

    2012-05-28

    Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required.

  20. METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Isayenko Ye. Yu

    2016-12-01

    Full Text Available Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount

  1. HPV Vaccine Safety PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  2. 9 CFR 113.64 - General requirements for live bacterial vaccines.

    Science.gov (United States)

    2010-01-01

    ... bacterial vaccines. 113.64 Section 113.64 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.64 General requirements for live bacterial vaccines... bacterial vaccine shall meet the requirements in this section. (a) Purity test. Final container samples...

  3. Enhancing vaccine safety capacity globally: A lifecycle perspective

    NARCIS (Netherlands)

    R.T. Chen (Robert T.); T.T. Shimabukuro (Tom T.); D.B. Martin (David); P. Zuber (Patrick); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

    2015-01-01

    textabstractMajor vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-p

  4. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  5. [Bacterial spore--a new vaccine vehicle--a review].

    Science.gov (United States)

    Wang, Yanchun; Zhang, Zhaoshan

    2008-03-01

    Bacterial spores are robust and dormant life forms with formidable resistance properties. Spores of the genus Bacillus have been used for a long time as probiotics for oral bacteriotherapy both in humans and animals. Recently, genetically modified B. subtilis spores and B. anthracis spores have been used as indestructible delivery vehicles for vaccine antigens. They were used as vaccine vehicles or spore vaccine for oral immunization against tetanus and anthrax, and the results were very exciting. Unlike many second generation vaccine systems currently under development, bacterial spores offer heat stability and the flexibility for genetic manipulation. At the same time, they can elicit mucosal immune response by oral and nasal administration. This review focuses on the use of recombinant spores as vaccine delivery vehicles.

  6. 76 FR 30722 - Meeting of the National Vaccine Advisory Committee; Vaccine Safety Working Group

    Science.gov (United States)

    2011-05-26

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the National Vaccine Advisory Committee; Vaccine Safety Working Group AGENCY... Department of Health and Human Services (DHHS) is hereby giving notice that the Vaccine Safety Working...

  7. Understanding Thimerosal, Mercury, and Vaccine Safety

    Science.gov (United States)

    ... fungus. It is used as a preservative for flu vaccines in multi-dose vials, to keep the vaccine ... as much as possible. • Today, except for some flu vaccines in multi-dose vials, no recommended childhood vaccines ...

  8. Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

    OpenAIRE

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee; Kang, Jin Han

    2010-01-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (

  9. Improving live attenuated bacterial carriers for vaccination and therapy.

    Science.gov (United States)

    Loessner, Holger; Endmann, Anne; Leschner, Sara; Bauer, Heike; Zelmer, Andrea; zur Lage, Susanne; Westphal, Kathrin; Weiss, Siegfried

    2008-01-01

    Live attenuated bacteria are well established as vaccines. Thus, their use as carriers for prophylactic and therapeutic macromolecules is a logical consequence. Here we describe several experimental applications of bacteria to carry heterologous macromolecules into the murine host. First, Listeria monocytogenes are described that are able to transfer eukaryotic expression plasmids into host cells for gene therapy. High multiplicities of infection are still required for efficient gene transfer and we point out some of the bottlenecks that counteract a more efficient transfer and application in vivo. Then, we describe Salmonella enterica serovar Typhimurium (S. typhimurium) as an expression plasmid transfer vehicle for oral DNA vaccination of mice. We demonstrate that the stabilization of the plasmid transformants results in an improved immune response. Stabilization was achieved by replacing the origin of replication of the original high-copy-number plasmid by a low-copy-number origin. Finally, we describe Salmonella carriers for the improved expression of heterologous proteins. We introduce a system in which the plasmid is carried as a single copy during cultivation but is amplified several fold upon infection of the host. Using the same in vivo inducible promoter for both protein expression and plasmid amplification, a substantial increase in antigen expression in vivo can be achieved. A modification of this approach is the introduction of inducible gene expression in vivo with a low-molecular-weight compound. Using P(BAD) promoter and L-arabinose as inducer we were able to deliberately activate genes in the bacterial carrier. No background activity could be observed with P(BAD) such that an inducible suicide gene could be introduced. This is adding an important safety feature to such live attenuated carrier bacteria.

  10. Vaccine safety--vaccine benefits: science and the public's perception.

    Science.gov (United States)

    Wilson, C B; Marcuse, E K

    2001-11-01

    The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.

  11. [Conjugate vaccines against bacterial infections: typhoid fever].

    Science.gov (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  12. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  13. Pertussis vaccine in pregnant women: safety and uptake

    Directory of Open Access Journals (Sweden)

    Munoz FM

    2016-03-01

    Full Text Available Flor M Munoz Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA Abstract: Pertussis continues to be an important cause of morbidity and mortality in children worldwide, particularly among infants too young to be vaccinated or who are unvaccinated and unprotected by naturally acquired passive antibodies from their mothers. Vaccination of women during pregnancy with an adult formulation of acellular pertussis vaccine in combination with tetanus and diphtheria toxoids (Tdap [tetanus, reduced diphtheria and acellular pertussis vaccine] is recommended in several industrialized countries to boost the levels of maternal antibodies that are transferred transplacentally and protect infants during the period of life when they are more likely to succumb to pertussis. Data from clinical and epidemiologic studies are supportive of the safety and effectiveness of maternal immunization with pertussis vaccines. Tdap is safe and well tolerated in pregnant women. Local and systemic reactogenicity is similar to that observed in nonpregnant adults, and no serious adverse events have been attributed to Tdap vaccination during pregnancy. Maternal antibodies elicited by the vaccine are efficiently transferred to the fetus through the placenta, and studies have consistently found that infants born to vaccinated mothers have significantly higher concentrations of pertussis antibodies than infants of nonvaccinated mothers. Although a correlate of protection against pertussis is unknown, higher concentrations of antibodies are likely to result in protection of young infants. A reduction in infant pertussis has been shown to occur when high vaccine coverage rates are achieved by pregnant women, as reported in the UK vaccination program. Furthermore, as more vaccine programs incorporate Tdap vaccination during pregnancy, prospective and epidemiologic data will be available to continuously assess the safety and efficacy of

  14. Bacterial derived proteoliposome for allergy vaccines.

    Science.gov (United States)

    Lastre, Miriam; Pérez, Oliver; Labrada, Alexis; Bidot, Igor; Pérez, Jorge; Bracho, Gustavo; del Campo, Judith; Pérez, Dainerys; Facenda, Elisa; Zayas, Caridad; Rodríguez, Claudio; Sierra, Gustavo

    2006-04-12

    One current approach in developing anti allergic vaccines is the use of potent adjuvants, capable of inducing Th1 or T regulatory cells. Proteoliposomes (PL) could be a suitable adjuvant. Purified Dermatophagoides siboney (Ds) allergens were mixed with PL and adsorbed into Al(OH)3 and evaluated in mice. The Th1/Th2 responses were measured at classes, subclasses, cytokines, and DTH levels. Anti Ds response was deviated to a Thl pattern, with the production of IgG2a and gamma1FN. A positive DTH response and a dramatic decrease of specific IgE and IL5 were not detected. The low dose was more effective than high dose. These results clearly support the potential use of PL as possible adjuvants for anti-allergic vaccines.

  15. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... pig. The requirements for general safety for inactivated influenza vaccine shall not be considered...

  16. BACTERIAL OUTER MEMBRANE VESICLES AND VACCINE APPLICATIONS

    Directory of Open Access Journals (Sweden)

    Reinaldo eAcevedo

    2014-03-01

    Full Text Available Vaccines based on outer membrane vesicles (OMV were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of self meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA, serogroup W (dOMVW and serogroup X (dOMVX were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC, Bordetella pertussis (dOMVBP, Mycobacterium smegmatis (dOMVSM and BCG (dOMVBCG. The immunogenicity of the OMV have been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice have shown their protective potential. dOMVB has been evaluated with non-self neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates.

  17. Generation of safety enhanced Edwardsiella tarda ghost vaccine.

    Science.gov (United States)

    Lee, Dong Jin; Kwon, Se Ryun; Zenke, Kosuke; Lee, Eun Hye; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

    2008-09-24

    A dual vector expressing the ghost-inducing PhiX174 lysis E gene and the bacterial DNA degrading staphylococcal nuclease A (SNA) gene was constructed to solve the problem of remnant antibiotic resistance genes and genomic DNA with intact pathogenic islands in the final product of Edwardsiella tarda ghosts (ETG). The SNA (devoid of secretion signal sequence and the nuclease B amino terminus sequence), fused with the 26 amino acid N-terminal sequence of the lambda phage Cro gene, showed successful degradation of bacterial nucleic acids. Furthermore, the nuclease activity of SNA in E. tarda was enhanced by codon optimization of the SNA gene using site-directed mutagenesis. ETG were generated via coexpression of the SNA gene and lysis gene E under the control of each lambdaP(R) promoter. The ghost bacteria generation system we describe is advantageous as it allows the use of a single plasmid, improves safety and vaccine purity by limiting residual genetic content from the ghost bacteria, and reduces production costs through cheap means of induction that use only temperature shifts.

  18. Safety Profile of the 9-Valent HPV Vaccine

    DEFF Research Database (Denmark)

    Moreira, Edson D; Block, Stan L; Ferris, Daron

    2016-01-01

    OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6....... More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive...... for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

  19. The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

    Directory of Open Access Journals (Sweden)

    Aimee Tan

    2016-12-01

    Full Text Available Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression, are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.

  20. Efficacy and safety of influenza vaccination in children with asthma.

    Science.gov (United States)

    Patria, Maria Francesca; Tenconi, Rossana; Esposito, Susanna

    2012-04-01

    The mean global prevalence of asthma among children is approximately 12%, making it the most common chronic disease in children. Influenza infection has been associated with complications such as exacerbations of wheezing and asthma, increased airway hyper-reactivity and hospitalization. Although influenza vaccination is recommended for asthmatic patients by all health authorities, vaccination coverage remains significantly lower than expected and is lowest of all in children. Compliance is affected by the uncertainty of parents and physicians concerning the clinical risk of influenza in asthmatic subjects, the benefits of influenza vaccination in preventing asthma exacerbations and the safety of immunization. The aim of this review is to analyze the rationale for using influenza vaccine, discuss the relationship between influenza and the severity of asthmatic episodes and document the efficacy and safety of influenza vaccination in the pediatric asthmatic population.

  1. Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

    NARCIS (Netherlands)

    Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole

    2011-01-01

    The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by man

  2. Vector Design for Improved DNA Vaccine Efficacy, Safety and Production

    Directory of Open Access Journals (Sweden)

    James A. Williams

    2013-06-01

    Full Text Available DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

  3. Current developments in avian influenza vaccines, including safety of vaccinated birds as food.

    Science.gov (United States)

    Swayne, D E; Suarez, D L

    2007-01-01

    Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced.

  4. Immunogenicity and safety of diphtheria-tetanus vaccine in adults.

    Science.gov (United States)

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee; Kang, Jin Han

    2010-12-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (antibody concentrations (≥ 0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

  5. Epidemiological designs for vaccine safety assessment: methods and pitfalls.

    Science.gov (United States)

    Andrews, Nick

    2012-09-01

    Three commonly used designs for vaccine safety assessment post licensure are cohort, case-control and self-controlled case series. These methods are often used with routine health databases and immunisation registries. This paper considers the issues that may arise when designing an epidemiological study, such as understanding the vaccine safety question, case definition and finding, limitations of data sources, uncontrolled confounding, and pitfalls that apply to the individual designs. The example of MMR and autism, where all three designs have been used, is presented to help consider these issues.

  6. Bacterial superglue enables easy development of efficient virus-like particle based vaccines

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa;

    2016-01-01

    BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...

  7. Parental views on vaccine safety and future vaccinations of children who experienced an adverse event following routine or seasonal influenza vaccination in 2010.

    Science.gov (United States)

    Parrella, Adriana; Gold, Michael; Marshall, Helen; Braunack-Mayer, Annette; Watson, Maureen; Baghurst, Peter

    2012-05-01

    To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.

  8. Molecular mimicry, inflammatory bowel disease, and the vaccine safety debate.

    Science.gov (United States)

    Yusung, Susy; Braun, Jonathan

    2014-09-18

    Preventive immunization has provided one of the major advances in population health during the past century. However, a surprising cultural phenomenon is the emergence of concerns about immunization safety, in part due to prominently controversial biomedical studies. One ongoing theoretical safety concern is the possibility of human molecular mimicry by measles, mumps, rubella (MMR) antigens. The study of Polymeros et al. in this BMC Medicine presents a systematic evaluation and refutation of this safety concern. This provides significant new scientific evidence in support of the safety of pediatric vaccines, which will inform the ongoing policy and cultural understanding of this important public health measure.

  9. Vaccine safety monitoring systems in developing countries: an example of the Vietnam model.

    Science.gov (United States)

    Ali, Mohammad; Rath, Barbara; Thiem, Vu Dinh

    2015-01-01

    Only few health intervention programs have been as successful as vaccination programs with respect to preventing morbidity and mortality in developing countries. However, the success of a vaccination program is threatened by rumors and misunderstanding about the risks of vaccines. It is short-sighted to plan the introduction of vaccines into developing countries unless effective vaccine safety monitoring systems are in place. Such systems that track adverse events following immunization (AEFI) is currently lacking in most developing countries. Therefore, any rumor may affect the entire vaccination program. Public health authorities should implement the safety monitoring system of vaccines, and disseminate safety issues in a proactive mode. Effective safety surveillance systems should allow for the conduct of both traditional and alternative epidemiologic studies through the use of prospective data sets. The vaccine safety data link implemented in Vietnam in mid-2002 indicates that it is feasible to establish a vaccine safety monitoring system for the communication of vaccine safety in developing countries. The data link provided the investigators an opportunity to evaluate AEFI related to measles vaccine. Implementing such vaccine safety monitoring system is useful in all developing countries. The system should be able to make objective and clear communication regarding safety issues of vaccines, and the data should be reported to the public on a regular basis for maintaining their confidence in vaccination programs.

  10. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible.

  11. Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

    Science.gov (United States)

    Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

    2011-05-01

    Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

  12. HPV Vaccine Safety PSA (:30) (No Tag)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. No CDC tag at the end. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  13. Safety and Efficacy of Vaccination Against Influenza in Patients With Rheumatoid Arthritis

    OpenAIRE

    Ori Elkayam

    2006-01-01

    Vaccination against influenza is currently recommended for patients with rheumatoid arthritis (RA). The safety and efficacy of vaccination in patients suffering from rheumatic diseases is still a matter of debate. This review summarizes the studies performed on the safety and immunogenicity of influenza vaccination in patients with RA as well as the rheumatic complications of the vaccine in otherwise healthy persons. Several trials have shown that the vaccine induces an adequate humoral respo...

  14. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine

    Science.gov (United States)

    Seo, Yu Bin; Lee, Jacob; Song, Joon Young; Choi, Hee Jung; Cheong, Hee Jin; Kim, Woo Joo

    2016-01-01

    Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIV-infected adults aged 18 – 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9μg) and a standard-content intradermal vaccine (IDflu15μg). Serum hemagglutination-inhibiting (HI) antibodies and INF-γ ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9μg, and 28 IDflu15μg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-γ ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50–60% and 2.5 – 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4+ T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose. PMID:26431466

  15. Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety

    Science.gov (United States)

    Tavana, Sasan; Argani, Hassan; Gholamin, Sharareh; Razavi, Seyed‐Mostafa; Keshtkar‐Jahromi, Marzieh; Talebian, Amir S.; Moghaddam, Keivan G.; Sepehri, Zahra; Azad, Talat M.; Keshtkar‐Jahromi, Maryam

    2011-01-01

    Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00290.x. Background  Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives  To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods  Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results  Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty‐four‐hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin‐converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare‐up was observed during follow‐up. Conclusions  In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs

  16. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.

    Science.gov (United States)

    Stowe, Julia; Andrews, Nick; Taylor, Brent; Miller, Elizabeth

    2009-02-25

    The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.

  17. A design thinking approach to effective vaccine safety communication.

    Science.gov (United States)

    Seeber, Lea; Michl, Bettina; Rundblad, Gabriella; Trusko, Brett; Schnjakin, Maxim; Meinel, Christoph; Weinberg, Ulrich; Gaedicke, Gerhard; Rath, Barbara

    2015-01-01

    The highly complex and controversial topic of vaccine safety communication warrants innovative, user-centered solutions that would start with gaining mutual respect while taking into account the needs, concerns and underlying motives of patients, parents and physicians. To this end, a non-profit collaborative project was conducted by The Vienna Vaccine Safety Initiative, an international think tank aiming to promote vaccine safety research and communication, and the School of Design Thinking in Potsdam, Germany, the first school for innovation in Europe. The revolutionary concept of the Design Thinking approach is to group students in small multi-disciplinary teams. As a result they can generate ground-breaking ideas by combining their expertise and different points of view. The team agreed to address the following design challenge question: "How might we enable physicians to encourage parents and children to prevent infectious diseases?" The current article describes, step-by step, the ideation and innovation process as well as first tangible outcomes of the project.

  18. Safety and Efficacy of Vaccination Against Influenza in Patients With Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ori Elkayam

    2006-01-01

    Full Text Available Vaccination against influenza is currently recommended for patients with rheumatoid arthritis (RA. The safety and efficacy of vaccination in patients suffering from rheumatic diseases is still a matter of debate. This review summarizes the studies performed on the safety and immunogenicity of influenza vaccination in patients with RA as well as the rheumatic complications of the vaccine in otherwise healthy persons. Several trials have shown that the vaccine induces an adequate humoral response and does not induce clinical exacerbation of RA. Rheumatic complications (mainly vasculitis following influenza vaccination in the general population are scarce.

  19. Bacterially produced recombinant influenza vaccines based on virus-like particles.

    Directory of Open Access Journals (Sweden)

    Andrea Jegerlehner

    Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

  20. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae.

    Science.gov (United States)

    O'Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-01-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

  1. Responding to vaccine safety signals during pandemic influenza: a modeling study.

    Directory of Open Access Journals (Sweden)

    Judith C Maro

    Full Text Available Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system.We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1 expected vaccination benefit from averted influenza; 2 expected vaccination risk from vaccine-associated febrile seizures; 3 expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4 expected change in vaccine-seeking behavior in future influenza seasons.Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior.The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.

  2. Risk perception, risk management and safety assessment: what can governments do to increase public confidence in their vaccine system?

    Science.gov (United States)

    MacDonald, Noni E; Smith, Jennifer; Appleton, Mary

    2012-09-01

    For decades vaccine program managers and governments have devoted many resources to addressing public vaccine concerns, vaccine risk perception, risk management and safety assessment. Despite ever growing evidence that vaccines are safe and effective, public concerns continue. Education and evidence based scientific messages have not ended concerns. How can governments and programs more effectively address the public's vaccine concerns and increase confidence in the vaccine safety system? Vaccination hesitation has been attributed to concerns about vaccine safety, perceptions of high vaccine risks and low disease risk and consequences. Even when the public believes vaccines are important for protection many still have concerns about vaccine safety. This overview explores how heuristics affect public perception of vaccines and vaccine safety, how the public finds and uses vaccine information, and then proposes strategies for changes in the approach to vaccine safety communications. Facts and evidence confirming the safety of vaccines are not enough. Vaccine beliefs and behaviours must be shaped. This will require a shift in the what, when, how and why of vaccine risk and benefit communication content and practice. A change to a behavioural change strategy such as the WHO COMBI program that has been applied to disease eradication efforts is suggested.

  3. Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

    NARCIS (Netherlands)

    R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    2006-01-01

    textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different r

  4. Safety evaluation in mice of the childhood immunization vaccines from two south-eastern states of Nigeria

    Directory of Open Access Journals (Sweden)

    Oli Angus Nnamdi

    2015-02-01

    Conclusions:: The vaccine samples tested were safe and did not affect the hematopoietic system adversely. The storage conditions of the vaccines in the States’ cold-chain stores had not compromised the safety of the vaccines.

  5. Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.

    Science.gov (United States)

    Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

    2015-01-01

    We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine.

  6. The effects of vaccination and immunity on bacterial infection dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Chris Coward

    2014-09-01

    Full Text Available Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.

  7. A New Method for the Evaluation of Vaccine Safety Based on Comprehensive Gene Expression Analysis

    Directory of Open Access Journals (Sweden)

    Haruka Momose

    2010-01-01

    Full Text Available For the past 50 years, quality control and safety tests have been used to evaluate vaccine safety. However, conventional animal safety tests need to be improved in several aspects. For example, the number of test animals used needs to be reduced and the test period shortened. It is, therefore, necessary to develop a new vaccine evaluation system. In this review, we show that gene expression patterns are well correlated to biological responses in vaccinated rats. Our findings and methods using experimental biology and genome science provide an important means of assessment for vaccine toxicity.

  8. SAFETY AND IMMUNOLOGIC EFFICACY OF COMBINED IMMUNIZATION IN CHILDREN AGED 6—7 YEARS WITH VACCINES FROM THE NATIONAL CALENDAR OF PROPHYLACTICS VACCINES

    Directory of Open Access Journals (Sweden)

    I. V. Konovalov

    2013-01-01

    Full Text Available We estimated the safety of the vaccination for prevention of influenza with Grippol® plus vaccine alongside with vaccination with combined preparations for the prevention of diphtheria and tetanus (Td and measles, rubella, mumps in children aged 6—7 years. We determined that combined immunization with the indicated vaccines proves good tolerability and low reactogenicity. Vaccine Grippol® Plus shows low reactogenicity , high immunologenicity and does not cause cross-suppression of antibodies in co-administration with other vaccines on vaccination calendar. Also concomitant vaccination with Grippol® plus and other vaccines does not inhibit the development of a specific immune response against influenza.

  9. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    Science.gov (United States)

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

  10. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    Directory of Open Access Journals (Sweden)

    Moataz Alhaj

    2016-01-01

    Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

  11. Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC oral cholera vaccine in pregnancy.

    Directory of Open Access Journals (Sweden)

    Ramadhan Hashim

    Full Text Available INTRODUCTION: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. METHODOLOGY/PRINCIPAL FINDINGS: From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151 in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94% of the target women in the study site were interviewed. 1,151 (79% of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83% out of these 1,151 mothers had not been vaccinated; the remaining 196 (17% mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. CONCLUSIONS/SIGNIFICANCE: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00709410.

  12. Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

    Directory of Open Access Journals (Sweden)

    Daniel Y. Bargieri

    2011-01-01

    Full Text Available In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines.

  13. The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

    OpenAIRE

    Aimee Tan; Atack, John M.; Jennings, Michael P; Seib, Kate L.

    2016-01-01

    Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, ...

  14. [Candid#1 vaccine against Argentine hemorrhagic fever produced in Argentina. Immunogenicity and safety].

    Science.gov (United States)

    Enria, Delia A; Ambrosio, Ana M; Briggiler, Ana M; Feuillade, María Rosa; Crivelli, Eleonora

    2010-01-01

    A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slightly higher than the efficacy estimated from previous studies (95.5%). There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine) were found for both vaccines. These included: headache, weakness, myalgias, mild low blood cell (ANMAT).

  15. Safety and effectiveness of MF-59 adjuvanted influenza vaccines in children and adults.

    Science.gov (United States)

    Black, Steven

    2015-06-01

    The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly.

  16. New adjuvanted vaccines in pregnancy : what is known about their safety?

    NARCIS (Netherlands)

    Herberts, Carla; Melgert, Barbro; van der Laan, Jan Willem; Faas, Marijke

    2010-01-01

    The recent introduction of oil-in-water emulsions as adjuvants in several pandemic vaccines, such as the H1N1 vaccine, has challenged regulatory authorities to establish their safety in the general population, as well as in specific populations. Pregnant women were advised to be a target group for H

  17. Preclinical and clinical safety studies on DNA vaccines.

    NARCIS (Netherlands)

    Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G

    2007-01-01

    DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clini

  18. The Role of Attitudes about Vaccine Safety, Efficacy, and Value in Explaining Parents' Reported Vaccination Behavior

    Science.gov (United States)

    LaVail, Katherine Hart; Kennedy, Allison Michelle

    2013-01-01

    Objectives: To explain vaccine confidence as it related to parents' decisions to vaccinate their children with recommended vaccines, and to develop a confidence measure to efficiently and effectively predict parents' self-reported vaccine behaviors. Method: A sample of parents with at least one child younger than 6 years ("n" = 376) was…

  19. Evaluation of the efficacy and safety of the Rift Valley Fever Clone 13 vaccine in sheep.

    Science.gov (United States)

    Dungu, Baptiste; Louw, Ian; Lubisi, Alison; Hunter, Pamela; von Teichman, Beate F; Bouloy, Michele

    2010-06-23

    The efficacy and safety of the naturally attenuated Rift Valley Fever (RVF) Clone 13 vaccine were evaluated in ovines in three different experiments involving 38 ewes at different stages of pregnancy, their offsprings and four rams. In Experiment 1, 4 rams and a total of 13 pregnant ewes were vaccinated and monitored during vaccination and after a challenge with a virulent RVF virus. The ewes were vaccinated at either 50 or 100 days of pregnancy and some were challenged after lambing. In Experiment 2, nine oestrus-synchronized ewes were vaccinated at 50 days of pregnancy and challenged at 100 days of pregnancy together with 5 unvaccinated ewes at the same stage of pregnancy. In Experiment 3, 16 oestrus-synchronized ewes were vaccinated with 3 different doses of the RVF Clone 13 vaccine and challenged together with unvaccinated pregnant ewes at either 30 or 50 days of pregnancy. The results from the three experiments indicated that the vaccine did not induce clinical manifestation of RVF such as abortion in pregnant ewes, teratogeny in their offsprings, or pyrexia in all vaccinated animals. Vaccination with RVF Clone 13 vaccine also prevented clinical RVF following virulent challenge at different stages of pregnancy while unvaccinated control ewes showed pyrexia, aborted or died of RVF. A vaccine dose-response effect was also observed.

  20. Bacterial vaccines in chronic obstructive pulmonary disease: effects on clinical outcomes and cytokine levels.

    Science.gov (United States)

    Ruso, Salvador; Marco, Francisco M; Martínez-Carbonell, Juan A; Carratalá, José A

    2015-07-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Exacerbation episodes impair lung function leading to disease progression. Levels of inflammation markers correlate with disease severity. Bacterial immunomodulators have shown a beneficial effect in COPD, improving symptoms and reducing the rate of exacerbations. This is an observational prospective study on 30 patients diagnosed with bronchiectasis and COPD, who received bacterial autogenous vaccine for 12 months. The rate of exacerbation, severity of symptoms and lung function were studied at baseline and after treatment. In addition, plasma levels CRP, IL6, IL8, and TNFα were measured. After treatment we found a reduction in mean acute respiratory infections and signs of lung disease. Acute phase proteins IL6 and CRP increased in blood and IL8 decreased. These changes may be related to the repeated injection of inactivated bacteria. Given the implication of these factors in the pathogenesis of COPD, particularly the production of IL8, the causes and consequences of cytokine modulation by bacterial vaccines should be investigated. Vaccination with autogenous vaccines for 1 year can produce a significant clinical improvement in COPD patients, reducing the frequency of exacerbations associated to changes in the profile of markers of inflammation.

  1. Production of a Recombinant Vaccine Candidate against Burkholderia pseudomallei Exploiting the Bacterial N-Glycosylation Machinery

    Directory of Open Access Journals (Sweden)

    Fatima eGarcia-Quintanilla

    2014-07-01

    Full Text Available Vaccines developing immune responses towards surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work we functionally expressed the B. pseudomallei O polysaccharide (OPS II, the C. jejuni oligosaccharyltransferase (OTase, and a suitable glycoprotein (AcrA in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future.

  2. Major bacterial diseases in aquaculture and their vaccine development

    Science.gov (United States)

    Aquaculture is emerging as the fastest growing food-producing industry in the world due to the increasing demand for food fish consumption. However, the intensive culture of food fish has led to outbreaks of various bacterial diseases, resulting in annual economic losses to the aquaculture industry ...

  3. Safety reporting in developing country vaccine clinical trials-a systematic review.

    Science.gov (United States)

    Muehlhans, Susann; Richard, Georgina; Ali, Mohammad; Codarini, Gabriela; Elemuwa, Chris; Khamesipour, Ali; Maurer, Wolfgang; Mworozi, Edison; Kochhar, Sonali; Rundblad, Gabriella; Vuitton, Dominique; Rath, Barbara

    2012-05-09

    With more vaccines becoming available worldwide, vaccine research is on the rise in developing countries. To gain a better understanding of safety reporting from vaccine clinical research in developing countries, we conducted a systematic review in Medline and Embase (1989-2011) of published randomized clinical trials (RCTs) reporting safety outcomes with ≥50% developing country participation (PROSPERO systematic review registration number: CRD42012002025). Developing country vaccine RCTs were analyzed with respect to the number of participants, age groups studied, inclusion of safety information, number of reported adverse events following immunization (AEFI), type and duration of safety follow-up, use of standardized AEFI case definitions, grading of AEFI severity, and the reporting of levels of diagnostic certainty for AEFI. The systematic search yielded a total number of 50 randomized vaccine clinical trials investigating 12 different vaccines, most commonly rotavirus and malaria vaccines. In these trials, 94,459 AEFI were reported from 446,908 participants receiving 735,920 vaccine doses. All 50 RCTs mentioned safety outcomes with 70% using definitions for at least one AEFI. The most commonly defined AEFI was fever (27), followed by local (16) and systemic reactions (14). Logistic regression analysis revealed a positive correlation between the implementation of a fever case definition and the reporting rate for fever as an AEFI (p=0.027). Overall, 16 different definitions for fever and 7 different definitions for erythema were applied. Predefined AEFI case definitions by the Brighton Collaboration were used in only two out of 50 RCTs. The search was limited to RCTs published in English or German and may be missing studies published locally. The reported systematic review suggests room for improvement with respect to the harmonization of safety reporting from developing country vaccine clinical trials and the implementation of standardized case definitions.

  4. Live attenuated HIV vaccines: predicting the tradeoff between efficacy and safety.

    Science.gov (United States)

    Blower, S M; Koelle, K; Kirschner, D E; Mills, J

    2001-03-13

    The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine-induced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.

  5. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China

    Science.gov (United States)

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe. PMID:28192490

  6. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

    Science.gov (United States)

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe.

  7. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis.

    Science.gov (United States)

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S

    2011-05-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  8. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

    Directory of Open Access Journals (Sweden)

    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  9. Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

    Science.gov (United States)

    2017-01-01

    Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly.

  10. Safety of pandemic H1N1 vaccines in children and adolescents

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractDuring the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adve

  11. Evaluation of the immunogenicity and safety of Brucella melitensis B115 vaccination in pregnant sheep.

    Science.gov (United States)

    Pérez-Sancho, Marta; Adone, Rosanna; García-Seco, Teresa; Tarantino, Michaela; Diez-Guerrier, Alberto; Drumo, Rosanna; Francia, Massimiliano; Domínguez, Lucas; Pasquali, Paolo; Álvarez, Julio

    2014-04-01

    In spite of its limitations, Rev.1 is currently recognized as the most suitable vaccine against Brucella melitensis (the causative agent of ovine and caprine brucellosis). However, its use is limited to young animals when test-and-slaughter programs are in place because of the occurrence of false positive-reactions due to Rev.1 vaccination. The B. melitensis B115 rough strain has demonstrated its efficacy against B. melitensis virulent strains in the mouse model, but there is a lack of information regarding its potential use in small ruminants for brucellosis control. Here, the safety and immune response elicited by B115 strain inoculation were evaluated in pregnant ewes vaccinated at their midpregnancy. Vaccinated (n=8) and non-vaccinated (n=3) sheep were periodically sampled and analyzed for the 108 days following inoculations using tests designed for the detection of the response elicited by the B115 strain and routine serological tests for brucellosis [Rose Bengal Test (RBT), Complement Fixation Test (CFT) and blocking ELISA (ELISAb)]. Five out of the 8 vaccinated animals aborted, indicating a significant abortifacient effect of B115 inoculation at midpregnancy. In addition, a smooth strain was recovered from one vaccinated animal, suggesting the occurrence of an in vivo reversion phenomenon. Only one animal was positive in both RBT and CFT simultaneously (91 days after vaccination) confirming the lack of induction of cross-reacting antibody responses interfering with routine brucellosis diagnostic tests in most B115-vaccinated animals.

  12. Ontology-supported research on vaccine efficacy, safety and integrative biological networks.

    Science.gov (United States)

    He, Yongqun

    2014-07-01

    While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms.

  13. Safety and efficacy of hepatitis A vaccine in children with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Hanaa Mostafa El-Karaksy; Manal Ismail El-Hawary; Nehal Mohammad El-Koofy; Rokaya El-Sayed; Mona Al-Saeed El-Raziky; Samah Asaad Mansour; Gamal Mohammad Taha; Fatma El-Mougy

    2006-01-01

    AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix:720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine,as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events,immediate or late, were reported by the mothers after each dose of the vaccine.CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

  14. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety

    DEFF Research Database (Denmark)

    Vichnin, Michelle; Bonanni, Paolo; Klein, Nicola P

    2015-01-01

    active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous...

  15. Identification of the serotypes of bacterial meningitis agents; implication for vaccine usage.

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Attarpour-Yazdi

    2014-08-01

    Full Text Available Bacterial meningitis is one of the most serious infections and should be treated as emergency. As it has significant morbidity and mortality throughout the world, every country should have precise information regarding the etiological agents of disease and populations at risk to design public health prevention strategy. In the present study in addition of evaluation of common etiological agents (Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in bacterial meningitis cases, we sero-grouped or serotyped the obtained agents in order to predict the usefulness of existing vaccines against bacterial meningitis.Cerebrospinal fluid of 182 suspected meningitis patients were collected, from which 114 cases were approved by biochemical, microbiological and molecular tests as bacterial meningitis. The isolated bacteria were serogrouped or serotyped to determine the dominant serotypes.Streptococcus pneumoniae accounted for 36%, Haemophilus influenza for 26% and Neisseria meningitidis for 14% of cases. From 13 serogroups of N. meningitides the most frequent serogroups, were meningococcus group B (51%, C(24% A (18%, Z(2%, W135 (1% and 3% was not identified. In H. influenzae group only serotype b (100% have been identified and in pneumococcal meningitis the most common serotype among our cases were 18C (44% followed by14 (17%, 19A (13%, 6A (9%, 7F (4%, 4(3%, 3 (3%, 9V (2%, 8 (2%, 23f (2%, 5 (1%.Since there is no nationwide mass immunization program for common agents of bacterial meningitis in Iran, the result of this study can be used to improve the existing vaccines to cover the detected serotypes and consequently reduce the incidence of bacterial meningitis.

  16. Safety of West Nile Virus vaccines in sandhill crane chicks

    Science.gov (United States)

    Olsen, G.H.; Miller, K.J.; Docherty, D.E.; Bochsler, V.S.; Folk, Martin J.; Nesbitt, Stephen A.

    2008-01-01

    West Nile virus arrived in North America in 1999 and has spread across the continent in the ensuing years. The virus has proven deadly to a variety of native avian species including sandhill cranes (Grus canadensis). In order to provide safe and efficacious protection for captive and released populations of whooping cranes (G. americana), we have conducted a series of four research projects. The last of these was a study of the effects of two different West Nile virus vaccines on young Florida sandhill crane (G. c. pratensis) chicks and subsequent challenge with the virus. We found that vaccinating crane chicks as early as day 7 post-hatch caused no adverse reactions or noticeable morbidity. We tested both a commercial equine vaccine West Nile - Innovator (Fort Dodge Laboratories, Fort Dodge, Iowa) and a new recombinant DNA vaccine (Centers for Disease Control). We had a 33% mortality in control chicks (n =6) from West Nile virus infection, versus 0% mortality in two groups of vaccinated chicks (n = 12), indicating the two vaccines tested were not only safe but effective in preventing West Nile virus.

  17. Ensuring the quality, potency and safety of vaccines during preclinical development.

    Science.gov (United States)

    Lebron, Jose A; Wolf, Jayanthi J; Kaplanski, Catherine V; Ledwith, Brian J

    2005-12-01

    There is an abundance of vaccines currently in development, with most of them exploring novel mechanisms, adjuvants and/or delivery systems not only for traditional prophylactic use, but also for therapeutic uses. As vaccines are generally administered to healthy individuals, ensuring their quality, potency and safety becomes crucial, especially prior to evaluation in humans. To ensure these key attributes, vaccine developers need to incorporate them as early in the development program as possible, starting in basic research and continuing through preclinical, clinical and postmarketing development. Fortunately for vaccine developers, ample guidance is available from various regulatory agencies to enlighten the long and arduous path of vaccine development. This review will highlight these regulatory expectations, and provide some clarity as to why they are in place.

  18. Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP.

    Science.gov (United States)

    Yee, Joann L; McChesney, Michael B; Christe, Kari L

    2015-10-01

    Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston-Zagreb strain virus that had been attenuated after 22 passages on human diploid cells.

  19. Bacterial antigen expression is an important component in inducing an immune response to orally administered Salmonella-delivered DNA vaccines.

    Directory of Open Access Journals (Sweden)

    Michelle E Gahan

    Full Text Available BACKGROUND: The use of Salmonella to deliver heterologous antigens from DNA vaccines is a well-accepted extension of the success of oral Salmonella vaccines in animal models. Attenuated S. typhimurium and S. typhi strains are safe and efficacious, and their use to deliver DNA vaccines combines the advantages of both vaccine approaches, while complementing the limitations of each technology. An important aspect of the basic biology of the Salmonella/DNA vaccine platform is the relative contributions of prokaryotic and eukaryotic expression in production of the vaccine antigen. Gene expression in DNA vaccines is commonly under the control of the eukaryotic cytomegalovirus (CMV promoter. The aim of this study was to identify and disable putative bacterial promoters within the CMV promoter and evaluate the immunogenicity of the resulting DNA vaccine delivered orally by S. typhimurium. METHODOLOGY/PRINCIPAL FINDINGS: The results reported here clearly demonstrate the presence of bacterial promoters within the CMV promoter. These promoters have homology to the bacterial consensus sequence and functional activity. To disable prokaryotic expression from the CMV promoter a series of genetic manipulations were performed to remove the two major bacterial promoters and add a bacteria transcription terminator downstream of the CMV promoter. S. typhimurium was used to immunise BALB/c mice orally with a DNA vaccine encoding the C-fragment of tetanus toxin (TT under control of the original or the modified CMV promoter. Although both promoters functioned equally well in eukaryotic cells, as indicated by equivalent immune responses following intramuscular delivery, only the original CMV promoter was able to induce an anti-TT specific response following oral delivery by S. typhimurium. CONCLUSIONS: These findings suggest that prokaryotic expression of the antigen and co-delivery of this protein by Salmonella are at least partially responsible for the successful

  20. New strategies for combination vaccines based on the extended recombinant bacterial ghost system.

    Science.gov (United States)

    Eko, F O; Witte, A; Huter, V; Kuen, B; Fürst-Ladani, S; Haslberger, A; Katinger, A; Hensel, A; Szostak, M P; Resch, S; Mader, H; Raza, P; Brand, E; Marchart, J; Jechlinger, W; Haidinger, W; Lubitz, W

    1999-03-26

    Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts have been produced from a great variety of bacteria and are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extents the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens, immunomodulators or other substances. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in bacterial candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying inserts of foreign epitopes of up to 600 amino acids within the flexible surface loop areas of the S-layer further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts do not need the addition of adjuvants to induce immunity in experimental animals they can also be used as carriers or targeting vehicles or as adjuvants in combination with subunit vaccines. Matrixes like dextran which can be used to fill the internal lumen of ghosts can be substituted with various ligands to bind the subunit or other materials of interest. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of ghosts and recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in the production of ghosts. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. As carriers of foreign

  1. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni.

    Science.gov (United States)

    O'Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Carlos Salazar, Juan; Montero, David

    2015-01-01

    In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral(®)), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed.

  2. Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits.

    Science.gov (United States)

    Choudhry, Azhar; Mathena, Julie; Albano, Jessica D; Yacovone, Margaret; Collins, Limone

    2016-08-31

    Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially

  3. Safety and immunogenicity of the DTP/HB /Hib combination vaccine: phase I study

    Directory of Open Access Journals (Sweden)

    Kusnandi Rusmil

    2013-11-01

    Full Text Available Background The World Health Organization (WHO has recommended the introduction of hepatitis B (HB and Haemophilus influenza type b (Hib vaccines into routine childhood vaccination programs. A new diptheria/tetanus/pertussis (DTP/hepatitis B/Hib pentavalent combination vaccine has been developed. Objective To evaluate the safety and immunogenicity of a new combination DTP/HB/Hib liquid vaccine in infants. Methods An open-label, uncontrolled, prospective intervention phase I study was conducted on 30 healthy infants aged 6−11 weeks. Each subject received 3 doses of DTP/HB/Hib vaccine, formulated by Bio Farma, 0.5 mL intramuscularly at the left anterolateral thigh region using a 25-gauge needle of 25 mm length. Subjects were followed for 1 month after administration of each vaccine dose to evaluate its safety, while serum anti-diphteria, tetanus, HBb, Hib, and pertussis antibodies were measured prior to the 1st dose and 1 month after the 3rd dose. Results Among 30 vaccinated subjects, 18 infants had fever within 24 hours after the first vaccination. Most cases of fever were mild in intensity and resolved within 24 hours. No other systemic or local reactions, or serious adverse events were observed in our subjects during the study. The immunogenicity results after 3rd vaccine dose showed that the geometric mean titer of the anti-polyribosylribitol phosphate (PRP antibody levels increased significantly from 0.0041μg/mL to 4.37 μg/mL after vaccination, and most infants had a fourfold or greater rise in antibody levels over their pre-injection levels. All subjects who received DTP/HB/Hib liquid vaccine had seroprotective antibodies against tetanus, diphtheria,a and hepatitis B, while 29/30 infants had seroprotective antibodies against pertussis. Conclusion This new diphtheria/tetanus/pertusis/hepatitis B/Hib combination vaccine has excellent safety profile and antibody responses in infants. These results encourage further clinical evaluation in

  4. Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review.

    Science.gov (United States)

    Gonçalves, Ana Katherine; Cobucci, Ricardo Ney; Rodrigues, Hugo Marcus; de Melo, Amanda Gosson; Giraldo, Paulo César

    2014-01-01

    Recently, many studies have evaluated HPV vaccine safety and adverse effects. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co., Inc., Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which HPV vaccines were compared with placebo regarding safety, tolerability and adverse effects. Studies were searched up to March 2013 in the databases: Pubmed, Embase, Scielo and Cancerlit. Odds Ratios (OR) of most incident adverse effects were obtained. Twelve reports, involving 29,540 subjects, were included. In the HPV 16/18 group, the most frequently reported events related to the vaccine were pain (OR 3.29; 95% CI: 3.00-3.60), swelling (OR 3.14; 95% CI: 2.79-3.53) and redness (OR 2.41; 95% CI: 2.17-2.68). For the HPV 6/11/16/18 group the events were pain (OR 2.88; 95% CI: 2.42-3.43) and swelling (OR 2.65; 95% CI: 2.0-3.44). Concerning the HPV 16/18 vaccine, pain was the most common outcome detected. These effects can be due to a possible VLP-related inflammation process. Fatigue was the most relevant general effect observed followed by fever, gastrointestinal symptoms, and headache. In the HPV 6/11/16/18 group, only general symptoms, pain and swelling were observed. Pain and swelling were the most frequent. Comparing HPV 16/18 to HPV 6/11/16/18 vaccines, the former presented more adverse effects, perhaps because there are many more trials evaluating the bivalent vaccine. Other studies are needed to clarify this issue.

  5. Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review

    Directory of Open Access Journals (Sweden)

    Ana Katherine Gonçalves

    2014-12-01

    Full Text Available Recently, many studies have evaluated HPV vaccine safety and adverse effects. Two vaccine shave been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co., Inc., Whitehouse Station, NJ. We have performed a systematic review of all randomized controlled trials in which HPV vaccines were compared with placebo regarding safety, tolerability and adverse effects. Studies were searched up to March 2013 in the databases: Pubmed, Embase, Scielo and Cancerlit. Odds Ratios (OR of most incident adverse effects were obtained. Twelve reports, involving 29,540 subjects, were included. In the HPV 16/18 group, the most frequently reported events related to the vaccine were pain (OR 3.29; 95% CI: 3.00–3.60, swelling (OR 3.14; 95% CI: 2.79–3.53 and redness (OR 2.41; 95% CI: 2.17–2.68. For the HPV 6/11/16/18 group the events were pain (OR 2.88; 95% CI: 2.42–3.43 and swelling (OR 2.65; 95% CI: 2.0–3.44. Concerning the HPV 16/18 vaccine, pain was the most common outcome detected. These effects can be due to a possible VLP-related inflammation process. Fatigue was the most relevant general effect observed followed by fever, gastrointestinal symptoms, and headache. In the HPV 6/11/16/18 group, only general symptoms, pain and swelling were observed. Pain and swelling were the most frequent. Comparing HPV 16/18 to HPV 6/11/16/18 vaccines, the former presented more adverse effects, perhaps because there are many more trials evaluating the bivalent vaccine. Other studies are needed to clarify this issue.

  6. Safety and tolerability of intradermal influenza vaccination in patients with cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    Arintaya Phrommintikul; Wanwarang Wongcharoen; Srun Kuanprasert; Narawudt Prasertwitayakij; Rungsrit Kanjanavanit; Siriluck Gunaparn; Apichard Sukonthasarn

    2014-01-01

    Background It is well-established that influenza vaccination reduces adverse cardiovascular outcomes in patients with cardiovascular diseases (CVD), however, the vaccine coverage rate in most countries remains low. The concern about the local adverse effects of intramus-cular injection, particularly in CVD patients receiving antithrombotic therapy, is one of the important impediments. This study was con-ducted to assess the safety, side effects and tolerability of intradermal influenza vaccine in CVD patients. Methods This was an observa-tional study in adult CVD patients who had undergone vaccination against seasonal influenza by intradermal vaccination between May 16th and May 30th, 2012 at Maharaj Nakorn Chiang Mai Hospital. The medical history, patients’ acceptability and adverse effects were collected using a written questionnaire completed by the patient immediately following vaccination and by a telephone survey eight days later. Results Among 169 patients, 52.1%were women and the mean age was 63 ± 12 years. Coronary artery disease, valvular heart disease and dilated cardiomyopathy were present in 121 (71.6%), 40 (23.7%) and 8 (4.7%), respectively. Antithrombotics were used in 89.3%. After vaccination, the pain score was 0, 1 or 2 (out of 10) in 44.4%, 15.1%, and 27.6%of the patients, respectively. Eight days after vaccination, the common adverse reactions were itching 19 (11.9%), swelling 9 (5.7%) and fatigue (4.7%). No hematoma or bruising was reported. Conclusions The intradermal influenza vaccination is safe and well tolerates with high rates of satisfaction in CVD patients. This technique should be useful in expanding influenza vaccine coverage.

  7. Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis.

    Science.gov (United States)

    Vélez, Iván D; Gilchrist, Katherine; Martínez, Sofía; Ramírez-Pineda, José R; Ashman, Jill A; Alves, Fabiana P; Coler, Rhea N; Bogatzki, Lisa Y; Kahn, Stuart J; Beckmann, Anna Marie; Cowgill, Karen D; Reed, Steven G; Piazza, Franco M

    2009-12-11

    Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 10 microg recombinant Leishmania polyprotein LEISH-F1 antigen [TSA+LmSTI1+LeIF]+25 microg MPL-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n=34), 10 microg LEISH-F1 protein alone (n=17), or saline placebo (n=17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1+MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania.

  8. [Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program].

    Science.gov (United States)

    Hernández-Ávila, Mauricio; Lazcano-Ponce, Eduardo; Hernández-Ávila, Juan Eugenio; Alpuche-Aranda, Celia M; Rodríguez-López, Mario Henry; García-García, Lourdes; Madrid-Marina, Vicente; López Gatell-Ramírez, Hugo; Lanz-Mendoza, Humberto; Martínez-Barnetche, Jesús; Díaz-Ortega, José Luis; Ángeles-Llerenas, Angélica; Barrientos-Gutiérrez, Tonatiuh; Bautista-Arredondo, Sergio; Santos-Preciado, José Ignacio

    2016-01-01

    Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that

  9. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    Science.gov (United States)

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-09

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations.

  10. Safety of attenuated smallpox vaccine LC16m8 in immunodeficient mice.

    Science.gov (United States)

    Yokote, Hiroyuki; Shinmura, Yasuhiko; Kanehara, Tomomi; Maruno, Shinichi; Kuranaga, Masahiko; Matsui, Hajime; Hashizume, So

    2014-09-01

    Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients.

  11. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    Science.gov (United States)

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-07

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied.

  12. Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease

    NARCIS (Netherlands)

    Holvast, A; Huckriede, A; Wilschut, J; Horst, G; De Vries, JJC; Benne, CA; Kallenberg, CGM; Bijl, M

    2006-01-01

    Objective: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. Methods: SLE patients (n = 56) and healthy controls (n = 18) were studied. All patients had quie

  13. Immuogenicity and safety of a natural rough mutant of Brucella suis as a vaccine for swine

    Science.gov (United States)

    The objective of the current study was to evaluate the safety, immunogenicity and clearance of the natural rough mutant of Brucella suis strain 353-1 (353-1) as a vaccine in domestic swine. In three studies encompassing 155 animals, pigs were inoculated with 353-1 by conjunctival (5 x 10**7 CFU), p...

  14. Efficacy and safety of a combined Porcine Circovirus and Mycoplasma hyopneumoniae vaccine in finishing pigs

    Directory of Open Access Journals (Sweden)

    Maarten Witvliet

    2015-01-01

    Full Text Available The safety and protective efficacy of a new one dose combination vaccine containing Porcine Circovirus type 2 (PCV2 and M. hyopneumoniae antigens – Porcilis® PCV M Hyo - was evaluated in laboratory studies and under field conditions. Vaccination resulted in a moderate temperature increase on the day of vaccination and mild systemic and local reactions were found in only a low percentage of the vaccinated pigs. The local reactions observed were small (max. 2 cm and transient (max. 1 day. In short term (onset of immunity and long term (duration of immunity challenge studies with the individual pathogens, the vaccine significantly reduced the PCV2 load in lymphoid tissue and lungs and M. hyopneumoniae-induced lung lesions. In a placebo-controlled field trial on a farm where both PCV2 and M. hyopneumoniae were present, vaccination of piglets at 3 weeks of age resulted in a reduction of PCV2 viremia and shedding and lower lung lesion scores at slaughter. In addition, a positive effect on the average daily weight gain (+ 34 g/day in the finishing phase was observed. It can therefore be concluded that this new ready to use combination vaccine is safe and efficacious against PCV2 and M. hyopneumoniae single and combined infections.

  15. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

    Directory of Open Access Journals (Sweden)

    Ivan Y. C. Lin

    2015-11-01

    Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

  16. Evaluating the safety and immunogenicity of yellow fever vaccines: a systematic review

    Directory of Open Access Journals (Sweden)

    Thomas RE

    2015-04-01

    Full Text Available Roger E Thomas Department of Family Medicine, G012 Health Sciences Center, University of Calgary Medical School, Calgary, AB, Canada Purpose: To review the safety and immunogenicity of yellow fever vaccines. Literature search: The Cochrane Library (including the Cochrane CENTRAL Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the NHS Database of Abstracts of Reviews of Effects; MEDLINE; EMBASE; BIOSIS Previews; Global Health; CAB Abstracts; and the Lilacs Database of Latin American and Caribbean literature were searched for individual studies and systematic reviews through January 1, 2015. Results: Six yellow fever vaccines are currently produced, and they are effective against all seven yellow fever virus strains. There is a 99.2% homology of the genome sequences of the six current vaccines. Four systematic reviews identified very small numbers of serious adverse events. A systematic review (updated of all published cases identified 133 serious adverse events that met the Brighton Collaboration criteria: 32 anaphylactic, 42 neurologic (one death, 57 viscerotropic (25 deaths, and two of both neurologic and viscerotropic SAEs. The Sanofi Pasteur Global Pharmacovigilance database reported 276 million doses of Stamaril™ distributed worldwide and identified 12 reports of yellow fever vaccine-associated viscerotropic disease (YEL-AVD, 24 of yellow fever vaccine-associated neurologic disease (YEL-AND, and 33 reports of anaphylaxis (many already published. The Biomanguinhos manufacturer's database reported 110 million doses distributed worldwide between 1999 and 2009, and the rate of YEL-AND was estimated at 0.084/100,000 doses distributed and YEL-AVD at 0.02/100,000 doses distributed. Conclusion: Reports of serious adverse events are mostly from travelers from developed countries, and there is likely serious underreporting for developing countries. On the basis of the published reports, the yellow fever vaccines are

  17. Bacterial virulence, proinflammatory cytokines and host immunity: how to choose the appropriate Salmonella vaccine strain?

    Science.gov (United States)

    Raupach, B; Kaufmann, S H

    2001-01-01

    Salmonella infection in its mammalian host can be dissected into two main components. The co-ordinate expression of bacterial virulence genes which are designed to evade, subvert or circumvent the host response on the one hand, and the host defence mechanisms which are designed to restrict bacterial survival and replication on the other hand. The outcome of infection is determined by the one which succeeds in disturbing this equilibrium more efficiently. This delicate balance between Salmonella virulence and host immunity/inflammation has important implications for vaccine development or therapeutic intervention. Novel Salmonella vaccine candidates and live carriers for heterologous antigens are attenuated strains with defined genetic modifications of metabolic or virulence functions. Although genetic defects of different gene loci can lead to similar degrees of attenuation, effects on the course of infection may vary, thereby altering the quality of the elicited immune response. Studies with gene-deficient animals indicate that Salmonella typhimurium strains with mutations in aroA, phoP/phoQ or ssrA/ssrB invoke different immune responses and that a differential repertoire of pro-inflammatory cytokines is required for clearance. Consequently, Salmonella mutants defective in distinct virulence functions offer the potential to specifically modulate the immune response for defined medical applications.

  18. Protectome analysis: a new selective bioinformatics tool for bacterial vaccine candidate discovery.

    Science.gov (United States)

    Altindis, Emrah; Cozzi, Roberta; Di Palo, Benedetta; Necchi, Francesca; Mishra, Ravi P; Fontana, Maria Rita; Soriani, Marco; Bagnoli, Fabio; Maione, Domenico; Grandi, Guido; Liberatori, Sabrina

    2015-02-01

    New generation vaccines are in demand to include only the key antigens sufficient to confer protective immunity among the plethora of pathogen molecules. In the last decade, large-scale genomics-based technologies have emerged. Among them, the Reverse Vaccinology approach was successfully applied to the development of an innovative vaccine against Neisseria meningitidis serogroup B, now available on the market with the commercial name BEXSERO® (Novartis Vaccines). The limiting step of such approaches is the number of antigens to be tested in in vivo models. Several laboratories have been trying to refine the original approach in order to get to the identification of the relevant antigens straight from the genome. Here we report a new bioinformatics tool that moves a first step in this direction. The tool has been developed by identifying structural/functional features recurring in known bacterial protective antigens, the so called "Protectome space," and using such "protective signatures" for protective antigen discovery. In particular, we applied this new approach to Staphylococcus aureus and Group B Streptococcus and we show that not only already known protective antigens were re-discovered, but also two new protective antigens were identified.

  19. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics.

    Science.gov (United States)

    Stephens, David S

    2011-01-01

    Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vaccine serotypes; the decrease in carriage is correlated with disease reduction in unvaccinated individuals, and the impact of herd immunity lasts for years. Based on these data, models for using herd immunity in vaccine-based prevention strategies are underway for control of meningitis in sub-Saharan Africa. Although the immunologic basis of herd immunity and impact on microbial biology need more study, protecting the unvaccinated by altering pathogen transmission dynamics is a powerful effect of PPCVs and increasingly important in vaccine introduction, implementation, and evaluation strategies.

  20. Immunity induced shortly after DNA vaccination of rainbow trout against rhabdoviruses protects against heterologous virus but not against bacterial pathogens

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja;

    2002-01-01

    It was recently reported that DNA vaccination of rainbow trout fingerlings against viral hemorrhagic septicaemia virus (VHSV) induced protection within 8 days after intramuscular injection of plasmid DNA. In order to analyse the specificity of this early immunity, fish were vaccinated with plasmid...... DNA encoding the VHSV or the infectious haematopoietic necrosis virus (IHNV) glycoprotein genes and later challenged with homologous or heterologous pathogens. Challenge experiments revealed that immunity established shortly after vaccination was cross-protective between the two viral pathogens...... whereas no increased survival was found upon challenge with bacterial pathogens. Within two months after vaccination, the cross-protection disappeared while the specific immunity to homologous virus remained high. The early immunity induced by the DNA vaccines thus appeared to involve short-lived non...

  1. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1986 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Kaattari, Stephen L.

    1987-06-01

    Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon of the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon of Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem,and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's third year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various chemical conjugates of Renibacterium salmoninarum cells and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (cellular proliferation), and the kinetics of mortality after Lethal injections of the bacterium. An important facet of this research is the identification and isolation of virulence factors. These studies are not only important to the dissection of the mechanism of pathogenesis of bacterial kidney disease, but the purification of such a factor(s) will insure the production of a more potent vaccine. The studies completed this year have: (1) identified antigenic material which protect; (2) identified antigenic material which can exacerbate the disease; (3) identified a possibly major mechanism of pathogenesis via the interference with antibody; (4) the general ability to produce delineated a western blot technique for identification of infected fish; (5) described the

  2. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1985 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Kaattari, Stephen L.

    1986-06-01

    Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's second year was to chemically modify the major antigens of Renibacteirium salmoninarum, immunize coho salmon (Oncorhynchus kisutch), and to test the immunogenicity of the preparations used. Immunogenicity of the antigenic material was tested by (1) admixture experiments, using whole KD cells with muramyl dipepetide, Vibrio anguillarum extract, E. coli lipopolysaccharide, or Mycobacterium tuberculosis in Freund's complete adjuvant. In addition to these goals a number of important techniques have been developed in order to facilitate the production of the vaccine. These procedures include: (1) the use of the soluble antigen for diagnosis in the ELISA and Western blot analysis, (2) detection of salmonid anti-KD antibodies by an ELISA technique, (3) detection of cellular immune responses to the soluble antigen, and (4) development of immersion challenge procedures for bacterial kidney disease (BKD).

  3. Biotechnology and DNA vaccines for aquatic animals

    Science.gov (United States)

    Kurath, G.

    2008-01-01

    Biotechnology has been used extensively in the development of vaccines for aquaculture. Modern molecular methods such as polymerase chain reaction (PCR), cloning and microarray analysis have facilitated antigen discovery, construction of novel candidate vaccines, and assessments of vaccine efficacy, mode of action, and host response. This review focuses on DNA vaccines for finfish to illustrate biotechnology applications in this field. Although DNA vaccines for fish rhabdoviruses continue to show the highest efficacy, DNA vaccines for several other viral and bacterial fish pathogens have now been proven to provide significant protection against pathogen challenge. Studies of the fish rhabdovirus DNA vaccines have elucidated factors that affect DNA vaccine efficacy as well as the nature of the fish innate and adaptive immune responses to DNA vaccines. As tools for managing aquatic animal disease emergencies, DNA vaccines have advantages in speed, flexibility, and safety, and one fish DNA vaccine has been licensed.

  4. Safety and tolerability of bivalent HPV vaccine: an Italian post-licensure study.

    Science.gov (United States)

    Gasparini, Roberto; Bonanni, Paolo; Levi, Miriam; Bechini, Angela; Boccalini, Sara; Tiscione, Emilia; Amicizia, Daniela; Lai, Piero Luigi; Sulaj, Klodiana; Patria, Antonio Giuseppe; Panatto, Donatella

    2011-01-01

    One of the most important scientific discoveries of the last century was that persistent infection by some types of HPV is a precondition for the development of cervical cancer. The oncogenic types of HPV are also associated with other tumours (vaginal, vulvar and anal carcinomas, tumours of the head and neck, urethra and penis). Two preventive vaccines are currently available (Cervarix and Gardasil). Both have shown very good efficacy, safety and tolerability profiles. Nonetheless, extensive vaccination requires long-term monitoring of safety and tolerability. The aim of our study was to evaluate the safety and tolerability of the bivalent vaccine Cervarix in Italy. Every participant in the study completed a questionnaire after each dose of vaccine received, with a view to recording adverse events during the first 7 days after vaccination. We registered local (pain, redness, swelling) and systemic symptoms (fever, headache, myalgia, fatigue, arthralgia, itching, gastrointestinal disorders, rash and urticaria). A total of 4,643 subjects were recruited. In all, 7,107 questionnaires were collected: 3,064 after the first dose, 2,367 after the second and 1,676 after the third. No serious adverse events were observed. The most frequent local symptom was pain at the injection site, while fatigue, headache and myalgia were the most common systemic reactions. Pain was reported more frequently after the first dose than after the others, while all the other local and general symptoms were reported most frequently after the third dose. Almost all of the local and general reactions proved to be of negligible intensity and duration and required no medical intervention. Our results show better tolerability of the vaccine in comparison with the data from some controlled clinical studies and from other surveillance programmes conducted internationally. That tolerability proved to be better than in clinical studies could be explained by the absence of the typical apprehension felt

  5. Safety of a Live Attenuated Infectious Bovine Rhinotracheitis Vaccine IBRV LNM Strain

    Institute of Scientific and Technical Information of China (English)

    Guo; Li; Wang; Wei; Zhang; Shuqin; Cheng; Shipeng; Wu; Hua

    2014-01-01

    The paper was to evaluate the vaccine safety,and to prevent public health risk due to virus spread,the approach vaccination of was adopted in this research; and neck intramuscular injection of IBRV LNM attenuated vaccine strain was carried out. Blind passage for three generations in animal has tested the reversion risk to virulence. A total of 14 healthy and weaning cows at 6- 8 month old were divided into three groups. The 1st reversion of virulence trials used 105. 0TCID50/mL neck intramuscular injection of IBRV LNM attenuated vaccine strain. Then,the nose swab samples were collected for continuous 14 days. After passed through 0. 45 μm filter membrane,nasal swabs mixture was prepared as the virulence test inoculum for next generation. The body temperature was detected and clinical observation was carried out for continuous 14 days after inoculation. The inoculation dose was 1ml / cattle. Blood was collected on the 0 and 14 thdays of animal vaccination. After serum isolation,it was used for the antibody detection of serum. Research results showed that no virus was isolated from the nasal swabs from the F2 generation; vaccinated animals did not show any clinical signs of IBR; serological testing of IBRV antibody was negative,which indicated that the strain-inoculated animals did had reversion of virulence in all three generations.

  6. Vaccination with recombinant Mycobacterium tuberculosis PknD attenuates bacterial dissemination to the brain in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Ciaran Skerry

    Full Text Available BACKGROUND: We have previously identified Mycobacterium tuberculosis PknD to be an important virulence factor required for the pathogenesis of central nervous system (CNS tuberculosis (TB. Specifically, PknD mediates bacillary invasion of the blood-brain barrier, which can be neutralized by specific antisera, suggesting its potential role as a therapeutic target against TB meningitis. METHODOLOGY/PRINCIPAL FINDINGS: We utilized an aerosol challenge guinea pig model of CNS TB and compared the protective efficacy of recombinant M. tuberculosis PknD subunit protein with that of M. bovis BCG against bacillary dissemination to the brain. BCG vaccination limited the pulmonary bacillary burden after aerosol challenge with virulent M. tuberculosis in guinea pigs and also reduced bacillary dissemination to the brain (P = 0.01. PknD vaccination also offered significant protection against bacterial dissemination to the brain, which was no different from BCG (P>0.24, even though PknD vaccinated animals had almost 100-fold higher pulmonary bacterial burdens. Higher levels of PknD-specific IgG were noted in animals immunized with PknD, but not in BCG-vaccinated or control animals. Furthermore, pre-incubation of M. tuberculosis with sera from PknD-vaccinated animals, but not with sera from BCG-vaccinated or control animals, significantly reduced bacterial invasion in a human blood-brain barrier model (P<0.01. CONCLUSION: Current recommendations for administering BCG at birth are based on protection gained against severe disease, such as TB meningitis, during infancy. We demonstrate that vaccination with recombinant M. tuberculosis PknD subunit offers a novel strategy to protect against TB meningitis, which is equivalent to BCG in a guinea pig model. Moreover, since BCG lacks the PknD sensor, BCG could also be boosted to develop a more effective vaccine against TB meningitis, a devastating disease that disproportionately affects young children.

  7. Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant U.S. Military Women and Their Newborns

    Science.gov (United States)

    2013-03-01

    Macdonald TM, Shakir S, Dryburgh M, Mantay BJ, McDonnell P, et al. Influenza H1N1 (swine flu ) vaccination : a safety surveillance feasibility study using...Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski

  8. Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

    Science.gov (United States)

    Bentsi-Enchill, Adwoa D; Schmitz, Julia; Edelman, Robert; Durbin, Anna; Roehrig, John T; Smith, Peter G; Hombach, Joachim; Farrar, Jeremy

    2013-05-28

    Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use.

  9. Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

    Science.gov (United States)

    Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

    2014-12-12

    A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts.

  10. Comparison between a conventional subunit vaccine and the MF59-adjuvanted subunit influenza vaccine in the elderly: an evaluation of the safety, tolerability and immunogenicity.

    Science.gov (United States)

    Sindoni, D; La Fauci, V; Squeri, R; Cannavò, G; Bacilieri, S; Panatto, D; Gasparini, R; Amicizia, D

    2009-06-01

    The objective of this study was to evaluate and compare the safety, tolerability and immunogenicity for two seasonal influenza subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal). A total of 195 subjects aged > or = 65 years were enrolled to receive one dose of vaccine intramuscularly, 96 were vaccinated with Fluad, 99 received Agrippal. Blood samples were taken from all subjects in order to assess their antibody titre by the haemagglutination inhibition assay (HI), before (Time 0) and after (Time 1: 28 +/- 7 days) vaccination, against the A/H3N2 (A/Moscow/10/99), A/H1N1 (A/New Caledonia/20/99) and B/Shandong/7/97 antigens contained in the influenza vaccine in the 2002/2003 influenza season for the northern hemisphere. A good humoral antibody response was detected for both vaccines, meeting all the criteria of EMEA. The number of subjects in whom > or = 4-fold increase in antibody titre was recorded, in comparison with the pre-vaccination value, proved to be lower in the group vaccinated with AgrippaPl than in those vaccinated with the adjuvated preparation. Fluad" exhibited better immunogenicity than Agrippal. This difference was probably linked to the potentiated immune stimulation exerted by the adjuvant molecules. These results take on a particular importance if we consider that the immune system is weaker in the elderly; the administration of an adjuvated vaccine in such subjects is clearly preferable in that it provides greater and more prolonged protection. Both vaccines were generally well tolerated; no severe adverse events occurred in any of the subjects vaccinated, confirming the excellent safety profile of Fluad and Agrippal.

  11. Research on vaccines during pregnancy: protocol design and assessment of safety.

    Science.gov (United States)

    Munoz, Flor M; Sheffield, Jeanne S; Beigi, Richard H; Read, Jennifer S; Swamy, Geeta K; Jevaji, Indira; Rasmussen, Sonja A; Edwards, Kathryn M; Fortner, Kimberly B; Patel, Shital M; Spong, Catherine Y; Ault, Kevin; Heine, R Philips; Nesin, Mirjana

    2013-09-13

    The Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health organized a series of conferences, entitled "Enrolling Pregnant Women in Clinical Trials of Vaccines and Therapeutics", to discuss study design and the assessment of safety in clinical trials conducted in pregnant women. A panel of experts was charged with developing guiding principles for the design of clinical trials and the assessment of safety of vaccines during pregnancy. Definitions and a grading system to evaluate local and systemic reactogenicity, adverse events, and other events associated with pregnancy and delivery were developed. The purpose of this report is to provide investigators interested in vaccine research in pregnancy with a basic set of tools to design and implement maternal immunization studies which may be conducted more efficiently using consistent definitions and grading of adverse events to allow the comparison of safety reports from different trials. These guidelines and safety assessment tools may be modified to meet the needs of each particular protocol based on evidence collected as investigators use them in clinical trials in different settings and share their findings and expertise.

  12. Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy.

    Science.gov (United States)

    Nakalembe, Miriam; Mirembe, Florence M; Banura, Cecily

    2015-01-01

    Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical

  13. Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

    OpenAIRE

    Jones, CE; Munoz, FM; Spiegel, HML; Heininger, U; Zuber, PLF; Edwards, KM; Lambach, P.; Neels, P; Kohl, KS; Gidudu, J; Hirschfeld, S; Oleske, JM; Khuri-Bulos, N.; Bauwens, J.; Eckert, LO

    2016-01-01

    Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies.\\ud \\ud The guidelines prop...

  14. The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933.

    Science.gov (United States)

    Bonah, Christian

    2005-12-01

    The anti-tuberculosis BCG (Bacille Calmette-Guérin) vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette's death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of the spacious and magnificent 'New laboratories for research on tuberculosis and the preparation of the BCG' within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend.

  15. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Science.gov (United States)

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-07

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes.

  16. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1987 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Kaattari, Stephen

    1988-06-01

    Bacterial kidney disease (BKD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's fourth year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various--chemical conjugates of Renibacterium salmoninarum cell and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (chemiluminescence), and the kinetics of mortality after lethal injections of the bacteria. The studies completed this year have: (1) identified immunization procedures which enhance the induction of high levels of antibody; (2) identified functionally distinct serum antibodies which may possess different abilities to protect salmon against BKD; (3) begun the isolation and characterization of anti-R. salmoninarum antibodies which may correlate with varying degrees of protection; (4) identified chemiluminescence as a potential method for assessing cellular immunity to bacterial kidney disease; and (5) characterized two monoclonal antibodies to R. salmoninarum which will be of benefit in the diagnosis of this disease.

  17. Improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design: the Phacilitate Vaccine Forum, Washington D.C. 2011.

    Science.gov (United States)

    Moldovan, Ioana R; Tary-Lehmann, Magdalena

    2011-06-01

    The 9th Annual Vaccine Forum organized by Phacilitate in Washington D.C. 2011 brought together 50+ senior level speakers and over 400 participants representing all the key stakeholders concerning vaccines. The main focus of the meeting was to define priorities in the global vaccines sector from funding to manufacturing and evaluation of vaccine efficacy. A special session was devoted to improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design. The current regulatory approach to clinical assay specification, validation and standardization that enable more direct comparisons of efficacy between trials was illustrated by the success in meningococcal vaccine development. The industry approach to validation strategies was exemplified by a new serologic test used on the diagnostic of pneumococcal pneumonia. The application of the Animal Rule to bridge clinical and non-clinical studies in botulism has allowed significant progress in developing one of the first vaccines to seek approval under the FDA Animal Efficacy Rule. An example of pushing the boundaries in the correlation of immunological responses and efficacy points was represented by a recent cell-based influenza vaccine for which the same correlates of protection apply as for the traditional, egg-based flue vaccine. In the field of HIV phase 2b studies are underway, based on promising results obtained with some vaccine candidates. The conclusion of this session was that creativity in vaccine design and evaluation is beneficial and can lead to innovative new vaccine designs as well as to validated assays to assess vaccine efficacy.

  18. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

    Science.gov (United States)

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

  19. The safety of measles vaccination%麻疹疫苗接种安全性

    Institute of Scientific and Technical Information of China (English)

    戴智勤

    2012-01-01

    Measles remains one of the major causes of death among young children. Measles vaccination is one of the best measures to prevent measles,The safety surveillance of measles vaccination is a key factor to ensure immunization program implementation. This paper reviews the safety of measles vaccination,the surveillance of and response strategies for adverse reactions following measles vaccination.%麻疹仍是造成幼儿死亡的主要原因之一,麻疹疫苗接种是预防麻疹最有效的施措之一,对麻疹疫苗接种的安全性监测是保证免疫计划实施的关键因素.此文阐述了麻疹疫苗接种的安全性、对麻疹疫苗接种不良反应的监测以及应对接种不良反应的策略.

  20. Immunogenicity and safety of the 9-valent HPV vaccine in men

    DEFF Research Database (Denmark)

    Castellsagué, X; Giuliano, A R; Goldstone, S

    2015-01-01

    OBJECTIVES: This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16-26 years of age (the population that was used to establish 9v......HPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. METHODS: This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men...... having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3-dose regimen (Day 1, Month 2, Month 6...

  1. Immunogenicity and safety of liposome-vaccine encapsulating hepatitis B surface antigen and phosphodiester CpG oligodeoxynucleotides

    Institute of Scientific and Technical Information of China (English)

    CHUN YAN HE; QING LIANG LIU

    2006-01-01

    CpG oligodeoxynucleotides (CpG ODN) as adjuvant have been extensively studied in recent years. Phosphodiester CpG ODN (PO CpG ODN) can perfectly mimic bacterial DNA in enhancing immune response but are vulnerable to nucleases in vivo. This study aimed to evaluate the immunostimu latory potential and safety of phosphodiester CpG ODN encapsulated in nonphospholipid liposomes.BALB/c mice were immunized intramuscularly with different formulations of liposomes, CpG ODN and hepatitis B surface antigen (HBsAg). The results demonstrated that the encapsulated PO CpG ODN were protected against rapid degradation in vivo and retained their adjuvant activity. PO CpG ODN encapsulated with HBsAg in liposomes induced strong Th1-biased or Th1/Th2 mixed humoral immune response in mice with the magnitude similar to their phosphothioate equivalent in the same formulation.High IFN-gamma production induced by this formulation confirmed the generation of strong cellular immune response. Additionally, co-delivery of HBsAg and PO CpG ODN improved the immune response over that obtained with separate delivery. Safety experiment showed that liposome-encapsulaed PO CpG ODN and HBsAg caused mild systemic and moderate local adverse reaction. In conclusion, our data shows that PO CpG ODN encapsulated in liposomes fully exhibit their Th1-type adjuvant activity and act as a potential adjuvant for vaccines.

  2. Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Zitzmann-Roth

    Full Text Available Conventional smallpox vaccines based on replicating vaccinia virus (VV strains (e.g. Lister Elstree, NYCBOH are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox vaccine candidate based on a non-replicating Modified Vaccinia Ankara (MVA poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial.Cardiac safety of one and two doses of MVA compared to placebo was assessed in 745 healthy subjects. Vaccinia-naïve subjects received either one dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo by subcutaneous injection four weeks apart; vaccinia-experienced subjects received a single dose of MVA. Solicited and unsolicited adverse events (AE and cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI were monitored after each injection.A total of 5 possibly related AESI (3 cases of palpitations, 2 of tachycardia were reported during the study. No case of myo- or pericarditis occurred. One possibly related serious AE (SAE was reported during the 6-month follow-up period (sarcoidosis. The most frequently observed AEs were injection site reactions.Vaccination with MVA was safe and well tolerated and did not increase the risk for development of myo-/pericarditis.ClinicalTrials.gov NCT00316524.

  3. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  4. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Kaattari, Stephen L.

    1989-08-01

    Bacterial kidney disease of salmonids is a very complex disease which appears to exploit a variety of pathogenic mechanisms. An understanding of these mechanisms is essential to the development of efficacious vaccines. It has become well established from the studies published .in this report and those of others that soluble antigens which are secreted by Renibacterium salmoninarum have toxigenic potential. If they are found to be responsible for mortality, the development of toxoid(s) could be paramount to the production of a vaccine. One must, however, be circumspect in producing a vaccine. A thorough knowledge, not only of the pathogen, but also of the immune system of the host is an absolute requirement. This becomes of particular importance when dealing with fish diseases, since the field of fish immunology is still within its infancy. This lack of knowledge is particularly felt when the induction of a prophylactic immune response concomitantly leads to pathological side effects which may be as destructive as the original infection. Indeed, it appears that some aspects of BKD may be due to the induction of hypersensitivity reactions. If such immunopathologies are expressed, it is prudent to thoroughly evaluate the nature of the immunoprophylaxis to insure that these harmful sequelae do not occur. Evaluation of a variety of antigens, adjuvants, immune responses, and survival data leads us to recommend that attempts at prophylaxis against BKD should center upon the elicitation of cellular immunity utilizing preparations of Mycobacterium chelonii. The choice of this species of mycobacteria was made because of its effectiveness, ease of maintenance and production, and the lack of need for its propagation within containment facilities. These assets are important to consider if large scale vaccine production is to be profitable. As can be seen from the data provided, M. chelonii alone is capable of producing prophylaxis to BKD, however, this is likely due to the

  5. Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock.

    Directory of Open Access Journals (Sweden)

    M Kariuki Njenga

    2015-03-01

    Full Text Available BACKGROUND: Although livestock vaccination is effective in preventing Rift Valley fever (RVF epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. METHODS: In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. RESULTS: In vaccinated goats (N = 72, 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77, 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42 did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2 in cattle, 90.0 (95% CI, 25.1 - 579.2 in goats, and 40.0 (95% CI, 16.5 - 110.5 in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. CONCLUSIONS: The results suggest RVF Clone 13 vaccine is safe to use and has high (>90% immunogenicity in sheep and goats but moderate (> 65% immunogenicity in cattle.

  6. Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

    Directory of Open Access Journals (Sweden)

    Reinaldo Menezes Martins

    2004-12-01

    Full Text Available The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang® were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B® was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70% met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566, children 1 to 10 years old (484, adolescents from 11 to 19 years (740, adults from 20 to 30 years (568, and adults from 31 to 40 years (396. Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults or 0, 1, and 7 months (children. Vaccine dose was intramuscular 10 µg (infants, children, and adolescents or 20 µg (adults. Percent seroprotection (assumed when anti-HBs titers were > 10mIU/ml and geometric mean titer (mIU/ml were: newborn infants, 93.7% and 351.1 (Butang® and 97.5% and 1530.6 (Engerix B®; children, 100% and 3600.0 (Butang® and 97.7% and 2753.1 (Engerix B®; adolescents, 95.1% and 746.3 (Butang® and 96% and 1284.3 (Engerix B®; adults 20-30 years old, 91.8% and 453.5 (Butang® and 95.5% and 1369.0 (Engerix B®; and adults 31-40 years old, 79.8% and 122.7 (Butang® and 92.4% and 686.2 (Engerix B®. There were no severe adverse events following either vaccine. The study concluded that Butang® was equivalent to Engerix B® in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

  7. EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

  8. Safety and immunogenicity of 3 seasonal trivalent influenza vaccines in the Chinese military

    Science.gov (United States)

    Gao, Dongqi; Yang, Huisuo; Deng, Bing; Yin, Gang; Song, Wenjing; Zhang, Haiyang; Li, Yapin

    2016-01-01

    ABSTRACT Influenza, caused by the influenza virus, is a contagious acute viral respiratory disease with a high incidence rate and wide and rapid spread. Influenza-related morbidity, mortality, and hospitalization rates remain high and are increasing continuously in high-risk groups, with a significant impact on human health and the economy. In order to evaluate the immunogenicity of 3 seasonal trivalent influenza vaccines in Chinese military, we conducted this field trial. We assessed the safety and immunogenicity of 3 seasonal trivalent influenza vaccines(TIVs)manufactured by GlaxoSmithKline(GSK), Beijing Sinovac Biotech (Sinovac), and Shenzhen Sanofi Pasteur (Pasteur) in healthy Chinese servicemen. We used theimported GSKTIV as the control, comparing it with the 2 domestic TIVs in a 1:1:1randomized, double-blind, controlled trial in a military command in Beijing. Healthy individuals, aged between 18 and 34 years, who had not received any influenza vaccine in the preceding3 years were enrolled and administered one dose of a TIV. Safety data were collected throughout the whole study (day 0 to day 30). Blood samples were collected to assess the subjects' immunogenicity before vaccination and 21 d after vaccination. In total, 292 subjects enrolled in the study. Twelve participants (4.1%) reported 12 adverse events. The incidence of adverse events was 1%, 5%, and7% for the GSK, Sinovac, and Pasteur TIVs, respectively. The reported injection-site reaction frequencies were similar for all 3 TIVs (p = 0.217). However, the proportion of systemic reactions was higher after the GSKTIV than after the Pasteur or Sinovac TIV (7.1% vs 3.1% or1%, respectively; p = 0.020). Three TIVs satisfied both the European and US Food and Drug Administration criteria for H1N1–179, H1N1–74, H3N2, and B strains based on the post vaccination sero-protection, the sero-conversion rate, and the geometric mean titer ratio. The Sinovac TIV, Pasteur TIV, and GSK TIV were well tolerated and

  9. Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Walraven Vanessa

    2011-07-01

    Full Text Available Abstract Background Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1 multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo vaccine candidates formulated as an equimolar mixture (DiCo mix in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51. Methods Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains. Results These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons. Conclusions The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

  10. Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver

    Directory of Open Access Journals (Sweden)

    D. Ajith Roni

    2013-01-01

    Full Text Available Introduction. Patients with chronic liver disease (CLD are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV infection. The literature has shown that hepatitis B vaccines are safe and effective in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20 mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured after 120 days. Results. 52 patients with mean age years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44% than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker.

  11. [Results of Russian multicenter trial of immunogenicity, reactogenicity and safety of new combination vaccine against hepatitis A and B (Twinrix)].

    Science.gov (United States)

    Tatochenko, V K; Il'ina, N I; Romanenko, V V; Alikova, O A; Fassakhov, R S; Miasnikova, T N; Patlusova, V V; Zima, Iu Iu; Reshetnikova, I D; Frolova, G S; Smolenov, I V

    2006-01-01

    Results of registration trial of combination vaccine for prevention of hepatitis A and B are presented. The trial was conducted in 5 centers of Russia in 2004-2005 with full accordance to good clinical practice requirements and standards for multicenter open randomized trials. Immunogenicity of studied combination vaccine Twinrix was evaluated in comparison with two simultaneously administered monovalent vaccines against hepatitis A and B (Havrix and Engerix-B) in 200 healthy subjects aged 18-40, which were seronegative to hepatitis A and B. Reactogenicity based on interviewed and non-interviewed symptoms ranged on intensity was assessed also. 1 month after completion of primary vaccination all subjects in both groups were seropositive to hepatitis A. Sero-protection level of antibodies to hepatitis B virus was detected in 98.9% of participants vaccinated with Twinrix and in 95.6% of participants vaccinated with Engerix-B and Havrix. Overall, reactogenicity of vaccines was minor, marked adverse events caused by vaccination were rare (approximately 1%). Study shows that combination vaccine against hepatitis A and B (Twinrix) at least non inferior in terms of immunogenicity, safety and tolerability to monovalent vaccines (Havrix and Engerix-B), were registered in Russia.

  12. Immunogenicity and safety of trivalent inactivated influenza vaccine: a randomized, double-blind, multi-center, phase 3 clinical trial in a vaccine-limited country.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Woo, Heung Jeong; Wie, Seong-Heon; Lee, Jin-Soo; Chung, Moon-Hyun; Kim, Yang Ree; Jung, Sook In; Park, Kyung-Hwa; Kim, Tae Hyong; Uh, Soo-Taek; Kim, Woo Joo

    2011-02-01

    Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic.

  13. Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis.

    Science.gov (United States)

    Setiawan, Didik; Luttjeboer, Jos; Pouwels, Koen B; Wilschut, Jan C; Postma, Maarten J

    2017-01-01

    Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information for Asian populations is lacking. We searched four electronic databases including PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov. We reviewed selected manuscripts and extracted the pooled relative risk (RR) from immunogenicity and safety information on HPV vaccination among women in Asian countries. We identified two quadrivalent-vaccine studies and eight bivalent-vaccine studies conducted in Asian countries. Analysis across these studies suggested that the HPV vaccines significantly enhanced HPV16- and HPV18-specific antibody among both uninfected (RR 85.69; 95% confidence interval (CI) 31.51-233.04 and 62.77; 95% CI 37.4-105.51) and infected individuals (RR 8.60; 95% CI 6.95-10.64 and RR 8.13; 95% CI 5.96-11.11). Furthermore, HPV vaccination among Asian populations has a favorable safety profile, with only slightly higher risks of local (RR: 1.89; 95% CI 1.65-2.17) and systemic (RR: 1.33; 95% CI 1.18-1.50) adverse events in vaccinated individuals compared with controls. For Asian populations, HPV vaccines enhance the level of HPV16- and HPV18-specific antibodies for both uninfected and infected individuals. Also, the risk of adverse events related to vaccination are acceptable. More data are needed to establish vaccine efficacy with regard to prevention of HPV infection and further outcomes including cervical intraepithelial neoplasia (CIN) and cervical cancer.

  14. Safety evaluation in mice of the childhood immunization vaccines from two south-eastern states of Nigeria

    Institute of Scientific and Technical Information of China (English)

    Oli; Angus; Nnamdi; Agu; Remigus; Uchenna; Oli; Ugochukwu; Chinedum; Nwoye; Charles; Ugochukwu; Ejiofor; Obiora; Shedrack; Esimone; Charles; Okechukwu

    2015-01-01

    Objective:To check the effects of the vaccines on the hematopoietic system and weight of mice after immunization.Methods:The study was done with the Expanded Programme on Immunization vaccines donated by the Ministries of Health of Abia and Imo States of Nigeria.The vaccines were collected from the cold-chain stores and transported in vaccine carriers to the cold-chain facility in Nnamdi Azikiwe University Teaching Hospital within 3 hours of collection.They were used to immunize a total of 160 mice.The Ethics Committee of Nnamdi Azikiwe University Teaching Hospital,Nnewi of Anambra State,Nigeria approved the protocol.Results:Mice body weight changes test showed that the mice all had increased body weight at Days 3 and 7 post-immunization and none died during the 7 d post-immunization observation.The percentage weight gains of the mice compared with the control were 69%.70%,64%.63%,65%and 68%for oral polio vaccine,diphtheria-pertussis-tetanus.bacillus CalmetteGuerin,measles,yellow fever and hepatitis B vaccines respectively collected from Imo State.The mice immunized with oral polio vaccine,pentavalent.bacillus Calmette-Guerin.measles,yellow fever and hepatitis B vaccines collected from Abia State had 123%.114%,121%.116%,142%and 119%weight gain respectively compared with the control.Leukocytosis promoting toxicity test showed that none of the vaccines was able to induce proliferation of leukocytes up to ten folds.Leukopenic toxicity test showed that all the vaccines had an leukopenic toxicity test value higher than 80%of the control(physiological saline).Conclusions:The vaccine samples tested were safe and did not affect the hematopoietic system adversely.The storage conditions of the vaccines in the States’ cold-chain stores had not compromised the safety of the vaccines.

  15. INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

    Directory of Open Access Journals (Sweden)

    Giuseppe La Torre

    2016-09-01

    Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.

  16. In a safety net population HPV4 vaccine adherence worsens as BMI increases.

    Directory of Open Access Journals (Sweden)

    Diane M Harper

    Full Text Available Obesity adversely inhibits antibody response to vaccination. Three doses of HPV4 may or may not provide adequate long term protection against HPV 16/18 in obese females. The aim of this study was to determine whether adherence to HPV4 vaccination in a safety net population was reduced with increasing body mass index (BMI.We designed a historical prospective study evaluating the number and dates of HPV4 dosing that occurred from July 1, 2006 through October 1, 2009 by the demographic characteristics of the 10-26 year old recipient females. The defined dosing intervals were adapted from the literature and obesity categories were defined by the WHO.1240 females with BMI measurements received at least one dose of HPV4; 38% were obese (class I, II and III and 25% were overweight. Females with normal BMI received on-time triplet dosing significantly more often than did the obese class II and III females (30% vs. 18%, p<0.001. Obese class II/III females have a significant 45% less chance of completing the on-time triplet HPV4 series than normal women (OR = 0.55, 95% CI: 0.37, 0.83. Pregnancy history has a significant influence on BMI and HPV4 dosing compliance in this safety net population where 71% had been gravid. Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR = 0.39, 95% CI: 0.16, 0.95.Obesity, as well as gravidity and Hispanic race, are risk factors for lack of HPV4 vaccine adherence among young females in a safety net population.

  17. Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults

    Science.gov (United States)

    Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

    2017-01-01

    ABSTRACT Background: An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). Methods: A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18–35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. Results: A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. Conclusion: In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed

  18. Age specific differences in efficacy and safety for the CYD-tetravalent dengue vaccine.

    Science.gov (United States)

    Wilder-Smith, Annelies; Massad, Eduardo

    2016-01-01

    CYD-TDV is the first dengue vaccine to have completed Phase 3 efficacy trials. Efficacy was consistently higher in those aged 9 and above for all variables studied: efficacy against virologically confirmed dengue of any severity and serotype, serotype specific efficacy, efficacy dependent on baseline seropositivity, efficacy against hospitalizations and efficacy against severe disease. Because of the higher efficacy and the absence of a safety signal, the age group with the best benefit of the use of CYD-TDV is individuals aged 9 and above - the age group for which licensure is now being sought.

  19. Phase I Safety and Immunogenicity Study of a Candidate Meningococcal Disease Vaccine Based on Neisseria lactamica Outer Membrane Vesicles▿

    Science.gov (United States)

    Gorringe, Andrew R.; Taylor, Stephen; Brookes, Charlotte; Matheson, Mary; Finney, Michelle; Kerr, Moyra; Hudson, Michael; Findlow, Jamie; Borrow, Ray; Andrews, Nick; Kafatos, George; Evans, Cariad M.; Read, Robert C.

    2009-01-01

    Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing ≥4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis. PMID:19553555

  20. Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.

    Science.gov (United States)

    Gorringe, Andrew R; Taylor, Stephen; Brookes, Charlotte; Matheson, Mary; Finney, Michelle; Kerr, Moyra; Hudson, Michael; Findlow, Jamie; Borrow, Ray; Andrews, Nick; Kafatos, George; Evans, Cariad M; Read, Robert C

    2009-08-01

    Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing > or =4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis.

  1. Bacterial superglue enables easy development of efficient virus-like particle based vaccines

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa

    2016-01-01

    , longevity and functional efficacy compared to corresponding vaccines employing monomeric proteins. The spy-VLP vaccines also effectively broke B cell self-tolerance and induced potent and durable antibody responses upon vaccination with cancer or allergy-associated self-antigens (PD-L1, CTLA-4 and IL-5...

  2. Influence of parenteral administration routes and additional factors on vaccine safety and immunogenicity: a review of recent literature.

    Science.gov (United States)

    Herzog, Christian

    2014-03-01

    Vaccines have to be administered via an appropriate route, i.e. a route, which is optimal regarding safety, immunogenicity and practicability. In addition, there are factors, such as body site, needle length, injection technique, depth of injection, type of antigen, vaccine formulation, adjuvants, age, sex, race/ethnicity, body mass, and pre-existing immunity, which can have an impact on the reactogenicity and tolerability and/or on the immunogenicity of a given vaccine. For parenteral vaccine administration there are currently three routes licensed: intramuscular, subcutaneous and intradermal, either by using conventional hypodermic needles or by using alternative or needle-free injection devices. The factors potentially impacting on the 'performance' of a given route of administration, as reported in recent literature, are outlined and discussed in view of their importance. These factors need to be accounted and controlled for when designing vaccine studies and should be reported in a transparent and standardised way in publications.

  3. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  4. Safety and vaccine efficacy of an attenuated Vibrio vulnificus strain with deletions in major cytotoxin genes.

    Science.gov (United States)

    Kim, Young Ran; Lee, Shee Eun; Kim, Jong Ro; Rhee, Joon Haeng

    2015-12-01

    Vibrio vulnificus is a human pathogen causing a rapidly progressing fatal septicemia. We have previously reported that a V. vulnificus large toxin RtxA1 causes programmed necrotic cell death through calcium-mediated mitochondrial dysfunction. Here we developed a live attenuated vaccine strain (CMM781) having deletions in three genes encoding major virulence factors: RTX cytotoxin (rtxA1), hemolysin/cytolysin (vvhA) and metalloprotease (vvpE) of a clinical isolate strain CMCP6. The CMM781 strain showed significant attenuation in cytotoxicity and mouse lethality. The safety of CMM781 was also confirmed by measuring the transepithelial electric resistance of Caco-2 cell monolayers. Intragastric immunization of mice with the live attenuated V. vulnificus strain resulted in induction of systemic and mucosal antibodies specific to the pathogen. Moreover, the vaccinated mice were protected from challenges with high doses of the virulent strain through various injection routes. These results suggest that CMM781 appears to be a safe and effective vaccine candidate that would provide significant protection against V. vulnificus infection.

  5. Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents.

    Science.gov (United States)

    Yoon, Seo Hee; Kim, Han Wool; Ahn, Jong Gyun; Kim, In Tae; Kim, Jong-Hyun; Kong, Kyoung Ae; Kim, Kyung-Hyo

    2016-01-01

    Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim™, Epaxal®, or Havrix®, 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim™, Epaxal®, and Havrix®, respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim™, Epaxal®, and Havrix® respectively. Avaxim™ was significantly more immunogenic than Epaxal® and Havrix®, whereas there were no significant differences in antibody responses between Epaxal® and Havrix®. Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470).

  6. Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12–24 months

    Directory of Open Access Journals (Sweden)

    Segeja Method D

    2009-07-01

    Full Text Available Abstract Background Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3, produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651. Methods This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 μg or 30 μg or a control vaccine (Engerix B. Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination. Results A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3, the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in

  7. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine.

    Science.gov (United States)

    Cooper, C L; Davis, H L; Morris, M L; Efler, S M; Krieg, A M; Li, Y; Laframboise, C; Al Adhami, M J; Khaliq, Y; Seguin, I; Cameron, D W

    2004-08-13

    CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine (Fluarix containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activity CPG 7909, except in individuals with pre-existing immunity to A/Sydney/5/97 strain (baseline HI activity titre >20), where there was a trend to higher HI activity with CPG 7909 (P = 0.06). The addition of CPG 7909 to the 1/10th dose of Fluarix did however result in significantly higher levels of IFN-gamma secretion from peripheral blood mononuclear cells recovered at 4 weeks and restimulated ex vivo with A/Beijing/262/95 (P = 0.048) and B/Harbin/7/94 (P = 0.0057), restoring these to the level seen with full-dose vaccine. These results suggest

  8. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1984 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Kaattari, Stephen L.

    1985-06-01

    The data presented here demonstrate that there is some variability to the antigenic structure of KDB. Although gel filtration of all antigenic preparations revealed a wide range of sizes for antigens, resolution on a denaturing gel revealed relatively few protein bands and immunological assays revealed the same (3) low number of antigens. It is of particular interest that there seems to be a protein of 60 kd in all preparations, but that there are not larger individual molecular species. This, in turn indicates that the larger molecular weight species detected in gel filtration are most likely aggregates or membrane fragments composed of a lower molecular weight subunit. Use of ultrafiltration of KDM-2 medium appears to be successful in eliminating contamination of high molecular weight material found in KDM-2. There appears to be no alteration in the number of soluble antigens produced by growth in either medium, nor in the number of proteins, as detected by SDS-PAGE. However, soluble antigens isolated from UF-KDM-2 does appear to have greater heterogeneity in their isoelectric focusing (IEF) patterns than those from UF-KDM-2. Also, although there does appear to be an extended lag period in KDB growth on UF-KDM-2, there is no alteration in final O.D. or wet weight of cells. Thus, it appears that UF-KDM-2 may be an alternate medium for those wishing to isolate purified bacterial proteins or antigens. ELISA assays have been developed for the detection of soluble KDB antigens. This system is currently being developed as a sensitive measure of the presence of soluble antigen in serum and tissues of fish. Such a sensitive assay may also allow for the detection of KD+ spawners by the testing of ovarian fluid or serum. ELISA assays have also been developed to detect antibodies to soluble and cellular antigens of KDB. These systems have been proven successful in the detection of rabbit and murine monoclonal antibodies against KDB antigens. Future work will develop the use

  9. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    Science.gov (United States)

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents.

  10. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  11. Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

    Science.gov (United States)

    Grigg, Patricia; Titong, Allison; Jones, Leslie A; Yilma, Tilahun D; Verardi, Paulo H

    2013-09-17

    Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

  12. The safety of DNA vaccines%DNA 疫苗接种的安全性

    Institute of Scientific and Technical Information of China (English)

    靳彦文; 马清钧

    2001-01-01

    Three major issues have been raised with respect to the safety of DNA vaccines .These are the potential for inducing a transformational event, possible unexpected adverse consequences of the persistent expression of a foreign antigen and the formation of anti DNA antibodies. The review based on the relevent research articles give a summary of knowledge of DNA vaccines' safety published during past years.%DNA疫苗的安全性问题主要有三个方面:转入体内的外源DNA有可能整合到宿主细胞基因组上,使宿主细胞抑癌基因失活或癌基因活化,使宿主细胞转化成癌细胞;外源抗原持续表达产生的不良后果;质粒DNA诱导的自身免疫反应。本文综合近年来有关文献对DNA疫苗安全性的研究作一概括性介绍。

  13. Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model

    Science.gov (United States)

    Soares, Thaigra S.; Silva, Ana Luiza T.; Giunchetti, Rodolfo C.; Takano, Maria A. S.; Akamatsu, Milena A.; Kubrusly, Flávia S.; Lúcio-Macarini, Fernanda; Raw, Isaias; Iourtov, Dmitri; Ho, Paulo Lee; Bueno, Lilian L.; Fujiwara, Ricardo T.; Volpato, Gustavo T.

    2017-01-01

    While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control—rats received saline; Adjuvant—rats received the adjuvant MPLA, and Vaccine—rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy. PMID:28249007

  14. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Angela Liao

    Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

  15. Immunogenicity and safety of a trivalent inactivated 2010-2011 influenza vaccine in Taiwan infants aged 6-12 months.

    Science.gov (United States)

    Hwang, Kao-Pin; Hsu, Yu-Lung; Hsieh, Tsung-Hsueh; Lin, Hsiao-Chuan; Yen, Ting-Yu; Wei, Hsiu-Mei; Lin, Hung-Chih; Chen, An-Chyi; Chow, Julie Chi; Huang, Li-Min

    2014-05-01

    This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6-12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6-12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6-12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6-12 months.

  16. Comparison of the safety and efficacy of a new live Salmonella Gallinarum vaccine candidate, JOL916, with the SG9R vaccine in chickens.

    Science.gov (United States)

    Matsuda, Kiku; Chaudhari, Atul A; Lee, John Hwa

    2011-09-01

    We evaluated a recently developed live vaccine candidate for fowl typhoid (FT)-JOL916, a lon/cpxR mutant of Salmonella Gallinarum (SG)-by comparing its safety and efficacy with that of the well-known rough mutant strain SG9R vaccine in 6-wk-old Hy-Line hens. Forty-five chickens were divided into three groups of 15 chickens each. The chickens were then intramuscularly inoculated with 2 x 10(7) colony-forming units (CFUs) of JOL916 (JOL916 group), 2 x 10(7) CFUs of SG9R (SG9R group), or phosphate-buffered saline (control group). After vaccination, no clinical symptoms were observed in any of the groups. No differences in body weight increase were detected among the three groups postvaccination. A cellular immune response was observed at 2 wk postvaccination (wpv) in the JOL916 group with the peripheral lymphocyte proliferation assay, whereas no response was detected in the SG9R group. Elevation of SG antigen-specific plasma immunoglobulin was observed 2 and 3 wpv in the JOL916 and SG9R vaccine groups, respectively. After virulent challenge on day 25 postvaccination, 0, 1, and 15 chickens in the JOL916 group, SG9R group, and control group, respectively, died by 12 days postchallenge; the death rate of the SG9R vaccine group was statistically similar to that of the JOL916 group. Postmortem examination revealed that the JOL916 vaccine offered more efficient protection than the SG9R vaccine, with significantly decreased hepatic necrotic foci scores, splenic enlargement scores, necrotic foci scores, and recovery of the challenge strain from the spleen. Vaccination with JOL916 appears to be safe and offers better protection than SG9R against FT in chickens.

  17. Evaluating the effectiveness, impact and safety of live attenuated and seasonal inactivated influenza vaccination: protocol for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study

    Science.gov (United States)

    Lone, Nazir I; Kavanagh, Kimberley; Robertson, Chris; McMenamin, Jim; von Wissmann, Beatrix; Vasileiou, Eleftheria; Butler, Chris; Ritchie, Lewis D; Gunson, Rory; Schwarze, Jürgen; Sheikh, Aziz

    2017-01-01

    Introduction Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. Methods and analysis Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. Ethics and dissemination We obtained approval from the National Research Ethics Service Committee, West Midlands—Edgbaston. The study findings will be presented at

  18. Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose

    Science.gov (United States)

    Zhang, Ming; Dong, Chunsheng; Xiong, Sidong

    2017-01-01

    Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development. PMID:28224119

  19. A DIVA vaccine for cross-protection against Salmonella

    Science.gov (United States)

    Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protection of animal health and enhancement of food safety. However, current vaccines for swine may only offer limited cross-protection agai...

  20. Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response.

    Science.gov (United States)

    Hashimoto, Naoya; Tsuboi, Akihiro; Kagawa, Naoki; Chiba, Yasuyoshi; Izumoto, Shuichi; Kinoshita, Manabu; Kijima, Noriyuki; Oka, Yoshihiro; Morimoto, Soyoko; Nakajima, Hiroko; Morita, Satoshi; Sakamoto, Junichi; Nishida, Sumiyuki; Hosen, Naoki; Oji, Yusuke; Arita, Norio; Yoshimine, Toshiki; Sugiyama, Haruo

    2015-06-01

    To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.

  1. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates.

    Science.gov (United States)

    Lukashevich, Igor S; Carrion, Ricardo; Salvato, Maria S; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

    2008-09-26

    A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.

  2. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

    Directory of Open Access Journals (Sweden)

    Daniel Tusé

    2015-01-01

    Full Text Available We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF. The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11 displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies.

  3. THE SAFETY OF HAEMOPHILUS INFLUENZAE TYPE B/POLYRIBOSYLRIBITOL PHOSPHATE-TETANUS (HIB/PRP-T VACCINE, PHASE I STUDY

    Directory of Open Access Journals (Sweden)

    Kusnandi Rusmil

    2015-09-01

    Full Text Available Objective: To assess the safety and immunogenicity of the Haemophilus influenzae type b/polyribosylribitol phosphate-Tetanus (Hib/PRP-T liquid vaccine in healthy adults. Methods: An open label prospective intervention phase I study was conducted in Dr. Hasan Sadikin General Hospital from November to December 2010. Healthy adults aged 18−40 years were eligible to participate. Participants received one dose of Hib/PRP-T liquid vaccine. Blood samples were taken before, 4 days, and 1 month after vaccination. For a 28-day period following vaccination, solicited adverse events were recorded in the subjects’ diary and assessed afterward. Results: No local reactions or immediate systemic events were observed during the 30-minute period after immunization. There were no serious local or systemic reactions in this study. All of local and systemic reactions observed were slight, transient, self-limiting, and lasting no more than 72 hours after the administration of the vaccine. These reactions resolved without any medical intervention. Hematological and biochemical indices before and 4 days after vaccination were in normal limits. All subjects reached protective levels of antibodies (seroprotectivity against Hib. All subjects demonstrated antibodies performing high bactericidal activities 1 month after immunization. Conclusions: This study demonstrates that liquid Hib/PRP-T vaccine is highly immunogenic and beneficially safe when administered to healthy adults.

  4. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Mahamadou A Thera

    Full Text Available BACKGROUND: The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. METHODOLOGY/PRINCIPAL FINDINGS: A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1 based on apical membrane antigen-1 (AMA-1 from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

  5. Comparison of the immunogenicity and safety of two different brands of salmonella typhi VI capsular polysaccharide vaccine

    Directory of Open Access Journals (Sweden)

    Sabitha P

    2004-04-01

    Full Text Available BACKGROUND: The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. Safeand immunologic vaccines have been developed based on purified VI polysaccharide. OBJECTIVE: To compare the immune response elicited by two different brands of Salmonella Vi capsular polysaccharide vaccine (ViCPS. SETTING AND DESIGN: Double blind, randomized (3:1, controlled, parallel, phase III study was conducted at two centres in India to compare the safety and immunogenicity of TypbarTM, the investigational vaccine with an already marketed vaccine "X", in healthy subjects aged between 12 -25 years. MATERIAL AND METHODS: A sample size of 184 subjects was calculated. Subjects were randomly distributed in two groups, immunized with single dose of TypbarTM or Vaccine "X". Serum samples were taken before 7 days and 4 weeks after immunization for the determination of antibodies to Vi polysaccharide, by ELISA method. Safety was assessed by physical examination, laboratory parameters before and after vaccination and by monitoring adverse events. Statistics: The geometric mean antibody titre (GMT 4 weeks after vaccination was compared from respective pre-vaccination values by Wilcoxon signed rank test. Geometric mean of antibody levels before and after immunization and the ratio between them (Mann-Whitney test, the Seroconversion rates (Z test of proportions and the adverse events (Fisher′s exact testand Chi square test, were compared between two groups. P value < 0.05 was considered statistically significant. P values and 95% confidence intervals were estimated in two-tailed fashion. RESULTS: 153 subjects (TypbarTM =116 and Vaccine "X" =37 were studied. 71.6% (95% CI=63.4%-79.8% and 75.7% (95% CI=64.9% - 89.5% were the seroconversion rates with TypbarTM and vaccine "X" respectively. The GMT values for Vi antibodies induced after TypbarTM and vaccine "X" were 10.23 TypbarTM and 13.46 mg

  6. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study.

    Directory of Open Access Journals (Sweden)

    Francesca Lombardi

    Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.

  7. Safety and risk assessment of the genetically modified Lactococci on rats intestinal bacterial flora.

    Science.gov (United States)

    Lee, Kai-Chien; Liu, Chin-Feng; Lin, Tzu-Hsing; Pan, Tzu-Ming

    2010-08-15

    The interaction between Lactococcus lactis NZ9000/pNZPNK and intestinal microflora was evaluated as a method to assess safety of genetically modified microorganisms (GMMs). L. lactis NZ9000/pNZPNK is one kind of GMM and able to produce the intracellular subtilisin NAT (nattokinase) under induction with nisin. The host strain L. lactis NZ9000 was a generally recognized as safe (GRAS) microorganism. Six groups of Wistar rats were orally administered with L. lactis NZ9000/pNZPNK and L. lactis NZ9000 for 6 weeks. Fecal and cecal contents were collected to determine the number of L. lactis NZ9000, L. lactis NZ9000/pNZPNK, Lactobacillus, coliform bacteria, beneficial bacteria Bifidobacterium and harmful bacteria Clostridium perfringens. The liver, spleen, kidney and blood were evaluated for the bacterial translocation. After 6 weeks consumption with GM and non-GM Lactococcus, no adverse effects were observed on the rat's body weight, hematological or serum biochemical parameters, or intestinal microflora. The bacterial translocation test showed that L. lactis NZ9000/pNZPNK did not translocate to any organ or blood. Bifidobacterium was significantly increased in feces after administration of both Lactococcus strains (L. lactis NZ9000 and L. lactis NZ9000/pNZPNK), while C. perfringens remained undetectable during the experiment. These results suggested that L. lactis NZ9000/pNZPNK could be safe in animal experiments and monitoring of the interaction between test strains and intestinal microflora might be applied as a method for other GMM safety assessments.

  8. Composite sequential Monte Carlo test for post-market vaccine safety surveillance.

    Science.gov (United States)

    Silva, Ivair R

    2016-04-30

    Group sequential hypothesis testing is now widely used to analyze prospective data. If Monte Carlo simulation is used to construct the signaling threshold, the challenge is how to manage the type I error probability for each one of the multiple tests without losing control on the overall significance level. This paper introduces a valid method for a true management of the alpha spending at each one of a sequence of Monte Carlo tests. The method also enables the use of a sequential simulation strategy for each Monte Carlo test, which is useful for saving computational execution time. Thus, the proposed procedure allows for sequential Monte Carlo test in sequential analysis, and this is the reason that it is called 'composite sequential' test. An upper bound for the potential power losses from the proposed method is deduced. The composite sequential design is illustrated through an application for post-market vaccine safety surveillance data.

  9. Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability.

    Directory of Open Access Journals (Sweden)

    Emilia Bigaeva

    Full Text Available QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™ from vaccine trials.A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs and their 95% confidence intervals (CIs were calculated using a random-effects model. Jadad scale was used to assess the study quality.Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04-6.24. No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10-15.35 and RR 2.55, 95% CI 1.41-4.59, respectively. ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08-10.97.Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the

  10. Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Mahamadou A Thera

    Full Text Available BACKGROUND: The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A in children exposed to seasonal falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: A Phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02(A is a recombinant protein (FMP2.1 based on apical membrane antigen 1 (AMA1 from the 3D7 clone of P. falciparum, formulated in the Adjuvant System AS02(A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. One hundred healthy Malian children aged 1-6 years were recruited into 3 cohorts and randomized to receive either 10 microg FMP2.1 in 0.1 mL AS02(A, or 25 microg FMP2.1 in 0.25 mL AS02(A, or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A, or rabies vaccine. Three doses of vaccine were given at 0, 1 and 2 months, and children were followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited symptoms for 30 days after each vaccination. Serious adverse events were assessed throughout the study. Transient local pain and swelling were common and more frequent in all malaria vaccine dosage groups than in the comparator group, but were acceptable to parents of participants. Levels of anti-AMA1 antibodies measured by ELISA increased significantly (at least 100-fold compared to baseline in all 3 malaria vaccine groups, and remained high during the year of follow up. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02(A vaccine had a good safety profile, was well-tolerated, and induced high and sustained antibody levels in malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2 efficacy trial in children at this site. TRIAL REGISTRATION: ClinicalTrials.gov NCT00358332 [NCT00358332].

  11. Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

    Directory of Open Access Journals (Sweden)

    Aruna Chandran

    2010-07-01

    Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

  12. Thimerosal-containing hepatitis B vaccine exposure is highly associated with childhood obesity: A case-control study using the vaccine safety datalink

    Directory of Open Access Journals (Sweden)

    David A Geier

    2016-01-01

    Full Text Available Background: Obesity among children and adolescents in the United States has tripled since 1980, and has become a major public health concern. Aims: The purpose of this study was to evaluate the potential relationship between exposure to organic mercury from Thimerosal-containing hepatitis B vaccines and the children′s subsequent risk of an obesity diagnosis. Materials and Methods: A hypothesis-testing, case-control study was undertaken to evaluate exposure to organic mercury from Thimerosal-containing hepatitis B vaccines, which were administered at specific intervals in the first 6 months of life, among cases diagnosed with childhood obesity and controls by examining automated medical records for children born from 1991 to 2000 who were continuously enrolled in the Vaccine Safety Datalink database. Results: This study found highly significant associations as follows. Cases diagnosed with obesity were significantly (P < 0.00001 more likely to have received greater exposure to organic mercury from Thimerosal-containing hepatitis B vaccines administered within the first month of life (odds ratio (OR =1.511, first 2 months of life (OR = 1.486, and first 6 months of life (OR = 3.795 than the controls. Similar outcomes were observed when the overall data were separated by gender. In a dose-response manner, cases diagnosed with obesity were significantly more likely than controls to have received greater exposure to organic mercury from Thimerosal-containing hepatitis B vaccines, which were administered within the first 6 months of life (OR = 1.0375 per μg of mercury, P < 0.00001. Conclusions: In a dose-response manner, the present study associates an increased organic mercury exposure from Thimerosal-containing hepatitis B vaccines with an increased risk of obesity diagnosis, and suggests that Thimerosal is an obesogen. The results are biologically plausible and future studies are needed to examine this phenomenon.

  13. Generation of a safety enhanced Salmonella Gallinarum ghost using antibiotic resistance free plasmid and its potential as an effective inactivated vaccine candidate against fowl typhoid.

    Science.gov (United States)

    Jawale, Chetan V; Chaudhari, Atul A; Lee, John Hwa

    2014-02-19

    A safety enhanced Salmonella Gallinarum (SG) ghost was constructed using an antibiotic resistance gene free plasmid and evaluated its potential as fowl typhoid (FT) vaccine candidate. The antibiotic resistance free pYA3342 plasmid possesses aspartate semialdehyde dehydrogenase gene which is complimentary to the deletion of the chromosomal asd gene in the bacterial host. This plasmid was incorporated with a ghost cassette containing the bacteriophage PhiX174 lysis gene E, designated as pJHL101. The plasmid pJHL101 was transformed into a two virulence genes-deleted SG. The SG ghosts with tunnel formation and loss of cytoplasmic contents were observed by scanning electron microscopy and transmission electron microscopy. The cell viability of the culture solution was decreased to 0% at 24h after the induction of gene E expression by an increase in temperature from 37°C to 42°C. The safety and protective efficacy of the SG ghost vaccine was further examined in chickens which were divided into three groups: group A (non-immunized control), group B (orally immunized), and group C (intramuscularly immunized). The birds were immunized at 7d of age. No clinical symptoms associated with FT such as anorexia, depression and greenish diarrhea were observed in the immunized chickens. Upon challenge with a virulent SG strain at 3 week post-immunization, the chickens immunized with the SG ghost via various routes were efficiently protected, as shown by significantly lower mortality and post-mortem lesions in comparison with control group. In addition, all the immunized chickens showed significantly higher antibody responses accompanied by a potent antigen-specific lymphocyte proliferative response along with significantly increased numbers of CD4⁺ and CD8⁺ T lymphocytes. Overall, our results provide a promising approach of generating SG ghosts using the antibiotic resistance free plasmid in order to prepare a non-living bacterial vaccine candidate which could be

  14. Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers

    Directory of Open Access Journals (Sweden)

    Miguel Tregnaghi

    2014-09-01

    Conclusions: MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed.

  15. Safety and immunogenicity of Ontario Rabies Vaccine Bait (ONRAB) in the first us field trial in raccoons (Procyon lotor).

    Science.gov (United States)

    Slate, Dennis; Chipman, Richard B; Algeo, Timothy P; Mills, Samuel A; Nelson, Kathleen M; Croson, Christopher K; Dubovi, Edward J; Vercauteren, Kurt; Renshaw, Randall W; Atwood, Todd; Johnson, Shylo; Rupprecht, Charles E

    2014-07-01

    In 2011, we conducted a field trial in rural West Virginia, USA to evaluate the safety and immunogenicity of a live, recombinant human adenovirus (AdRG1.3) rabies virus glycoprotein vaccine (Ontario Rabies Vaccine Bait; ONRAB) in wild raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). We selected ONRAB for evaluation because of its effectiveness in raccoon rabies management in Ontario and Quebec, Canada, and significantly higher antibody prevalence rates in raccoons compared with a recombinant vaccinia-rabies glycoprotein (V-RG) vaccine, Raboral V-RG®, in US-Canada border studies. Raccoon rabies was enzootic and oral rabies vaccination (ORV) had never been used in the study area. We distributed 79,027 ONRAB baits at 75 baits/km(2) mostly by fixed-wing aircraft along parallel flight lines at 750-m intervals. Antibody prevalence was significantly higher at 49.2% (n=262) in raccoons after ONRAB was distributed than the 9.6% (n=395) before ORV. This was the highest antibody prevalence observed in raccoons by US Department of Agriculture Wildlife Services for areas with similar management histories evaluated before and after an initial ORV campaign at 75 baits/km(2) with Raboral V-RG. Tetracycline biomarker (TTCC) was significantly higher among antibody-positive raccoons after ONRAB baiting and was similar among raccoons before ORV had been conducted, an indication of vaccine-induced rabies virus-neutralizing antibody production following consumption of bait containing TTCC. Skunk sample size was inadequate to assess ONRAB effects. Safety and immunogenicity results supported replication of this field trial and led to a recommendation for expanded field trials in 2012 to evaluate safety and immunogenicity of ground-distributed ONRAB at 150 baits/km(2) in residential and commercial habitats in Ohio, USA and aerially distributed ONRAB at 75 baits/km(2) in rural habitats along US-Quebec border.

  16. Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

    Directory of Open Access Journals (Sweden)

    Partha Basu

    2013-01-01

    Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

  17. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  18. Immunization. Safety and Use of Polio Vaccines. Briefing Report to the Chairman, Subcommittee on Natural Resources, Agriculture Research and Environment, Committee on Science, Space, and Technology, House of Representatives.

    Science.gov (United States)

    General Accounting Office, Washington, DC.

    This report presents information on the status of the safety and use of polio vaccines in the United States. Topics discussed include: (1) the role of the Food and Drug Administration (FDA) in processing an inactivated polio vaccine license application; (2) the steps the federal government has taken to improve the safety of the vaccine; (3) the…

  19. Guillain-Barre Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011.

    Directory of Open Access Journals (Sweden)

    Sharon K Greene

    Full Text Available Guillain-Barré Syndrome (GBS can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1 pandemic in the United States, monovalent inactivated influenza vaccine (MIV availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV, and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI, 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior

  20. Immunogenicity and safety of a tetravalent dengue vaccine during a five-year follow-up period

    Directory of Open Access Journals (Sweden)

    Maria Rosario Capeding

    2015-01-01

    Full Text Available This study assessed the safety and persistence of dengue neutralising antibodies for five years after administration of a recombinant live, attenuated, tetravalent dengue vaccine (TDV. Participants aged 2–45 years (n = 126 were randomised at a single centre in the Philippines to receive TDV vaccinations at months 0, 3–4, and 12 (TDV–TDV–TDV group or licensed typhoid vaccination (TyVi at month 0 and TDV at months 3–4 and 12 (TyVi–TDV–TDV group. Dengue antibodies were measured annually (plaque reduction neutralisation test. Participants with suspected dengue underwent laboratory testing. No safety concerns were reported throughout the study. Six dengue cases were virologically confirmed, but assessed as non-severe dengue disease. Geometric mean titres throughout the follow-up period remained 2- to 4-fold higher than at baseline for all serotypes, ages and study groups. Approximately 10% of participants annually were exposed to wild-type dengue, which contributed to persistently higher titres compared with non-infected participants. In conclusion, TDV appears to have good safety and persistence of antibodies over five years.

  1. The Effect of Falsely Balanced Reporting of the Autism-Vaccine Controversy on Vaccine Safety Perceptions and Behavioral Intentions

    Science.gov (United States)

    Dixon, Graham; Clarke, Christopher

    2013-01-01

    Controversy surrounding an autism-vaccine link has elicited considerable news media attention. Despite being widely discredited, research suggests that journalists report this controversy by presenting claims both for and against a link in a relatively "balanced" fashion. To investigate how this reporting style influences judgments of vaccine…

  2. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Sophia Gailhardou

    2016-07-01

    Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

  3. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials

    Science.gov (United States)

    Gailhardou, Sophia; Skipetrova, Anna; Dayan, Gustavo H.; Jezorwski, John; Saville, Melanie; Van der Vliet, Diane; Wartel, T. Anh

    2016-01-01

    A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2–16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2–60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2–60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target population for vaccination (≥9 years old) for which CYD-TDV has a satisfactory safety profile. Long-term safety will continue to be monitored in the ongoing follow-up of efficacy trials. Safety and effectiveness in real-life settings

  4. Glyceradehyde-3-phosphate dehydrogenase as a suitable vaccine candidate for protection against bacterial and parasitic diseases.

    Science.gov (United States)

    Perez-Casal, Jose; Potter, Andrew A

    2016-02-17

    The enzyme glyceraldehyde-3-P-dehydrogenase (GAPDH) has been identified as having other properties in addition to its key role in glycolysis. The ability of GAPDH to bind to numerous extracellular matrices, modulation of host-immune responses, a role in virulence and surface location has prompted numerous investigators to postulate that GAPDH may be a good vaccine candidate for protection against numerous pathogens. Although immune responses against GAPDH have been described for many microorganisms, vaccines containing GAPDH have been successfully tested in few cases including those against the trematode-Schistosoma mansoni, the helminth-Enchinococcus multilocularis; the nematode filaria- Litomosoides sigmodontis; fish pathogens such as Aeromonas spp., Vibrio spp., Edwarsiella spp., and Streptococcus iniae; and environmental streptococci, namely, Streptococcus uberis and Streptococcus dysgalactiae. Before GAPDH-based vaccines are considered viable options for protection against numerous pathogens, we need to take into account the homology between the host and pathogen GAPDH proteins to prevent potential autoimmune reactions, thus protective GAPDH epitopes unique to the pathogen protein must be identified.

  5. 流感疫苗接种安全性的研究%Study on the safety of influenza vaccination

    Institute of Scientific and Technical Information of China (English)

    寇妍

    2011-01-01

    季节性流行性感冒(流感)是一种常见的呼吸道传染病,人群发病率高、传染性强、危害大,接种流感疫苗是预防流感及减少流感传播的有效措施.因<2岁婴儿、>65岁老年人、妊娠妇女及鸡蛋过敏人群感染流感病毒后出现并发症风险大、病死率高或易出现接种不良反应,视为特殊人群.随着流感疫苗生产水平的提高及人们埘流感疫苗研究的深入,特殊人群接种流感疫苗的安全性及有效性受到人们的重视.该文综述目前常用流感疫苗生产的相关研究及其在特殊人群中接种安全性的研究.%Seasonal influenza is a common respiratory infectious disease with high morbidity and strong infectivity, and it is harmful to people. Influenza vaccination is an effective measure to prevent influenza and reduce the spread of the influenza. People who are in great risk of influenza or tend to have adverse reactions should be considered as a special population, including the young child less than 2 years, the men or women older than 65 years, children with egg allergy and pregnant women. The attitudes about the safety and efficacy of influenza vaccine in special populations should be changed following the improvement of the influenza vaccine production and the deeply research. This paper reviewed the production of common flu vaccines and the safety of influenza vaccination in special populations.

  6. Assessments of global drivers of vaccine hesitancy in 2014—Looking beyond safety concerns

    Science.gov (United States)

    de Cola, Monica; MacDonald, Noni E.; Dumolard, Laure; Duclos, Philippe

    2017-01-01

    Vaccine hesitancy has become the focus of growing attention and concern globally despite overwhelming evidence of the value of vaccines in preventing disease and saving the lives of millions of individuals every year. Measuring vaccine hesitancy and its determinants worldwide is important in order to understand the scope of the problem and for the development of evidence-based targeted strategies to reduce hesitancy. Two indicators to assess vaccine hesitancy were developed to capture its nature and scope at the national and subnational level to collect data in 2014: 1) The top 3 reasons for not accepting vaccines according to the national schedule in the past year and whether the response was opinion- or assessment-based and 2) Whether an assessment (or measurement) of the level of confidence in vaccination had taken place at national or subnational level in the previous 5 years. The most frequently cited reasons for vaccine hesitancy globally related to (1) the risk-benefit of vaccines, (2) knowledge and awareness issues, (3) religious, cultural, gender or socio-economic factors. Major issues were fear of side effects, distrust in vaccination and lack of information on immunization or immunization services. The analysis revealed that 29% of all countries had done an assessment of the level of confidence in their country, suggesting that vaccine confidence was an issue of importance. Monitoring vaccine hesitancy is critical because of its influence on the success of immunization programs. To our knowledge, the proposed indicators provide the first global snapshot of reasons driving vaccine hesitancy and depicting its widespread nature, as well as the extent of assessments conducted by countries. PMID:28249006

  7. Vaccines.gov

    Science.gov (United States)

    ... supported by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on time can protect your child from serious diseases. Protect your community! Did you ...

  8. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  9. Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7

    Science.gov (United States)

    Hanke, Christiane R.; Grijalva, Carlos G.; Chochua, Sopio; Pletz, Mathias W.; Hornberg, Claudia; Edwards, Kathryn M.; Griffin, Marie R.; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Klugman, Keith P.; Vidal, Jorge E.

    2016-01-01

    Background Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine-types but little data exists from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, two years after PCV7 was introduced. Methods Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were quellung-serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by qPCR. Results The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (p=0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (p=0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increased density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were non-susceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%). Conclusions Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density. PMID:26974749

  10. Safety, immunogenicity and efficacy of a recombinant tetravalent dengue vaccine: a meta-analysis of randomized trials.

    Science.gov (United States)

    da Costa, Vivaldo G; Marques-Silva, Ariany C; Floriano, Vitor G; Moreli, Marcos L

    2014-09-03

    The World Health Organization has stipulated a target: reduce the mortality rate caused by dengue disease by 50% until 2020. Most likely, this goal can be achieved by means of a dengue vaccine. Accordingly, the recombinant and tetravalent dengue vaccine (CYD-TDV), developed by the Sanofi Pasteur Group, is in an advanced stage of human testing. Although there are multiple randomized, placebo-controlled trials evaluating the CYD-TDV, individual results may have little power to identify differences between the populations studied. Thus, we conducted a meta-analysis to determine a more precise estimate of the overall parameters of safety, immunogenicity and efficacy of CYD-TDV. A data search was conducted in the PubMed, Medline, Cochrane Central Register of Controlled Trials and SciELO databases with defined selection criteria. We included for meta-analysis seven randomized and placebo-controlled studies that included 6678 patients randomized to receive the CYD-TDV (4586) or placebo (2092). Regarding vaccine safety, it was found that there was no significant difference between treated and placebo groups, as only approximately 5.5% of patients were withdrawn from the study. Regarding immunogenicity, the levels of neutralizing antibodies were measured by weighted mean differences (WMD), which were always higher in the vaccinated group (WMD/DENV1=59.7, 95% confidence interval [CI] 57-61; WMD/DENV2=99, 95% CI 95-102; WMD/DENV3=138, 95% CI 133-142; WMD/DENV4=123, 95% CI 119-126). The clinical efficacy of the vaccine was 59% (95% CI 15-80; RR=0.41, 95% CI 0.2-0.85, I(2)=30.9%). In conclusion, safety and a balanced immune response to the CYD-TDV were found. However, to fully establish the clinical effectiveness and robustness of immunogenicity, it is necessary to perform further studies to assess the long-term effects of the vaccine.

  11. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines.

    Science.gov (United States)

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara

    2015-03-10

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines.

  12. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study

    OpenAIRE

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2015-01-01

    abstract The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese ch...

  13. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

    Directory of Open Access Journals (Sweden)

    Robert L Seymour

    Full Text Available Chikungunya virus (CHIKV is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK, a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/- knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

  14. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

    Science.gov (United States)

    Seymour, Robert L; Adams, A Paige; Leal, Grace; Alcorn, Maria D H; Weaver, Scott C

    2015-01-01

    Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

  15. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    Science.gov (United States)

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  16. Safety and Immunogenicity of an Inactivated Whole Cell Plus Recombinant B Subunit (WC/RBS) Cholera Vaccine in Healthy Adult Peruvian Military Volunteers.

    Science.gov (United States)

    1992-11-30

    AD-A260 586 IFB0 919931 MIPR NO: 92MM2532W TITLE: SAFETY AND IMMUNOGENICITY OF AN INACTIVATED WHOLE CELL PLUS RECOMBINANT B SUBUNIT (WCIRBS) COLERA ...NUMBERS Safety and Immunogenicity of an Inactivated Whole MIPR No. Cell Plus Recombinant B Subunit (WC/RBS) Colera 92MM2532 Vaccine in Healthy Adult

  17. Safety and immunogenicity of Onderstepoort Biological Products’ Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal

    Directory of Open Access Journals (Sweden)

    Modou M. Lo

    2015-02-01

    Full Text Available This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV Clone 13 vaccine (Onderstepoort Biological Products to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05. No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group, 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05. The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer’s instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.

  18. Safety and immunogenicity of Onderstepoort Biological Products' Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal.

    Science.gov (United States)

    Lo, Modou M; Mbao, Victor; Sierra, Pascale; Thiongane, Yaya; Diop, Mariame; Donadeu, Meritxell; Dungu, Baptiste

    2015-05-29

    This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV) Clone 13 vaccine (Onderstepoort Biological Products) to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats) were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo) only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05). No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group), 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05). The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer's instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.

  19. Recent trends in pediatric bacterial meningitis in Japan--a country where Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines have just been introduced.

    Science.gov (United States)

    Shinjoh, Masayoshi; Iwata, Satoshi; Yagihashi, Tatsuhiko; Sato, Yoshitake; Akita, Hironobu; Takahashi, Takao; Sunakawa, Keisuke

    2014-08-01

    To investigate the trends in incidence and the characteristics of bacterial meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7-valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010, respectively, which was 5-20 years after their introduction in western countries. The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was performed in 2011 and 2012. We analyzed the epidemiological and clinical data, and compared the information obtained in the previous nationwide survey database. We also investigated the risk factors for disease outcome. In the 2011-2012 surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae, Streptococcus agalactiae and Escherichia coli were the main organisms. The number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.31 in 2009 to 0.43 in 2012 (p influenzae and S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30 to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2012. The median patient age was 10-12 months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001-2012 among the four organisms. Risk factors for death and sequelae were convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children.

  20. Bacterial superglue enables easy development of efficient virus-like particle based vaccines

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa;

    2016-01-01

    for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP...... components. RESULTS: Genetic fusion of SpyTag or SpyCatcher to the N-terminus and/or C-terminus of the Acinetobacter phage AP205 capsid protein resulted in formation of stable, nonaggregated VLPs expressing one SpyCatcher, one SpyTag or two SpyTags per capsid protein. Mixing of spy-VLPs with eleven different...... vaccine antigens fused to SpyCatcher or SpyTag resulted in formation of antigen-VLP complexes with coupling efficiencies (% occupancy of total VLP binding sites) ranging from 22-88 %. In mice, spy-VLP vaccines presenting the malaria proteins Pfs25 or VAR2CSA markedly increased antibody titer, affinity...

  1. [Safety and tolerability of monovalent measles and combined measles, mumps, rubella, and varicella vaccines].

    Science.gov (United States)

    Mentzer, D; Meyer, H; Keller-Stanislawski, B

    2013-09-01

    Although effective monovalent and combined measles vaccines have been available for several decades in Germany, measles outbreaks continue to occur leading to severe cases of measles and even death. Possible reasons for the low acceptance of the measles vaccination are concerns about adverse events and serious complications following vaccination. In this report, we have summarized and assessed all adverse events reported in Germany from 2001 to 2012 after vaccination with monovalent- and combined measles-containing vaccines. A total of 1,696 suspected adverse reaction reports describing 5,297 adverse events were sent to the Paul Ehrlich Institute (PEI) between 1 January 2001 and 31 December 2012. The calculated mean reporting rate was 5.7 reports per 100,000 vaccine doses released by the PEI. Analysis of the reports indicates that measles-containing vaccines are well tolerated with a constantly low rate of adverse events reported. Compared to the high rate of serious complications following wild-type measles infection, the benefit of measles-containing vaccines clearly outweighs the anticipated risks of adverse events.

  2. Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men.

    Science.gov (United States)

    Imoukhuede, E B; Berthoud, T; Milligan, P; Bojang, K; Ismaili, J; Keating, S; Nwakanma, D; Keita, S; Njie, F; Sowe, M; Todryk, S; Laidlaw, S M; Skinner, M A; Lang, T; Gilbert, S; Greenwood, B M; Hill, A V S

    2006-10-30

    We assessed the safety and immunogenicity of prime-boost vectors encoding the Plasmodium falciparum circumsporozoite (CS) protein expressed either in the attenuated fowl-pox virus (FP9) or modified vaccinia virus Ankara (MVA). Thirty-two adult Gambians in groups of four to eight received one, two or three doses of FP9 CS and/or MVA CS. No serious adverse event was observed following vaccination. The most immunogenic regimen was two doses of FP9 followed by a single dose of MVA 4 weeks later (an average of 1000 IFN-gamma spot forming units/million PBMCs). This level of effector T-cell responses appears higher than that seen in previously reported studies of CS-based candidate malaria vaccines.

  3. Use of the self-controlled case-series method in vaccine safety studies: review and recommendations for best practice.

    Science.gov (United States)

    Weldeselassie, Y G; Whitaker, H J; Farrington, C P

    2011-12-01

    The self-controlled case-series method was originally developed to investigate potential associations between vaccines and adverse events, and is now commonly used for this purpose. This study reviews applications of the method to vaccine safety investigations in the period 1995-2010. In total, 40 studies were reviewed. The application of the self-controlled case-series method in these studies is critically examined, with particular reference to the definition of observation and risk periods, control of confounders, assumptions and potential biases, methodological and presentation issues, power and sample size, and software. Comparisons with other study designs undertaken in the papers reviewed are also highlighted. Some recommendations are presented, with the emphasis on promoting good practice.

  4. Bacterial Meningitis after Cochlear Implantation among Children without Polyvalent Conjugate Vaccine: A Brief Report of an Iranian Cohort Study on 371 Cases

    Directory of Open Access Journals (Sweden)

    Shahla Afsharpaiman

    2014-01-01

    Full Text Available Background: Regarding risk of bacterial meningitis (BM after Cochlear implantation (CI, it was suggested to receive polyvalent conjugate vaccine. We aimed to estimate the prevalence of BM post CI in child recipients who do not receive polyvalent vaccine. Methods: We enrolled 371 children who had received cochlear implants from 2007 to 2010. None of them received pre or post implantation polyvalent conjugate vaccine for BM. We followed all of them for BM for 2 years after implantation. Results: We detected only one female case of BM (0.3% of patients with the age of 24 months. The mean age of noninfected children was 36.7 ± 23.2 months. The education level of parents was "college level or higher" in less than half of them, and about 65% of patients were products of consanguineous marriage. Conclusions: Our findings indicated that the incidence of BM was not higher in our cochlear implanted children who did not receive immunization than patients from countries in which routine vaccination is done. We suggest that although proper immunization is recommended before surgery, this procedure could be performed without vaccination, especially in developing countries that face financial problems for preparing vaccines.

  5. Safety and efficacy of yellow fever vaccine in children less thanone-year-old.

    Science.gov (United States)

    Osinusi, K; Akinkugbe, F M; Akinwolere, O A; Fabiyi, A

    1990-01-01

    In a clinical trial of stabilized yellow fever vaccine from Institute Pasteur in 77 children aged seven to eight months, fever was the most significant immediate and delayed side effect. Fever occurred in 12 (15.6%) children with in 48 hours of vaccination while it occurred in 10 (12.9%) children within ten days of vaccination. Other recorded side effects were pain at innoculation site in four (5.2%) children and vomiting in one (1.3%) child. Temperature recorded in 20 of the 22 febrile episodes ranged from 37.8 degrees C to 38.6 degrees C. One of the two patients who had temperatures of 39 degrees C and above had malaria parasites in her blood film. All episodes of fever except one responded to antipyretic. There was no episode of febrile convulsion and no feature suggestive of encephalitis. Of the 20 children who had neutralization test carried out against yellow fever virus six weeks after vaccination, the test was positive in post vaccination sera of 12 (60%) children whose pre-vaccination sera were negative. Two others showed evidence of partial protection. Although the seroconversion rate of 60% is less than reported in adults and older children, the result of this study shows that yellow fever vaccine is safe and fairly effective in infants. It is our suggestion that if a larger trial confirms our findings, the vaccine may be incorporated into the expanded programme on immunization (EPI) to be given at the age of seven months after completion of diptheria, tetanus, pertussis and poliomyelitis vaccinations and before measles vaccination is due.

  6. Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses

    Directory of Open Access Journals (Sweden)

    Sykes Alma

    2011-10-01

    Full Text Available Abstract Background WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT. However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Methods Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Results Over the course of one year, 965 children were enrolled; 158 (16.4% were RDT-positive and treated with artemether-lumefantrine and 807 (83.4% were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6% children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2% children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9% children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7 and specificity of 96.3% (95%CI 96.3-98.4. Conclusions Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive

  7. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

    Science.gov (United States)

    Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

    2016-01-01

    Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

  8. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-03

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.

  9. Safety and colonization of two novel VirG(IcsA)-based live Shigella sonnei vaccine strains in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Collins, Todd A; Barnoy, Shoshana; Baqar, Shahida; Ranallo, Ryan T; Nemelka, Kevin W; Venkatesan, Malabi M

    2008-02-01

    Shigella are gram-negative bacterium that cause bacillary dysentery (shigellosis). Symptoms include diarrhea and discharge of bloody mucoid stools, accompanied by severe abdominal pain, nausea, vomiting, malaise, and fever. Persons traveling to regions with poor sanitation and crowded conditions become particularly susceptible to shigellosis. Currently a vaccine for Shigella has not been licensed in the United States, and the organism quickly becomes resistant to medications. During the past 10 y, several live attenuated oral Shigella vaccines, including the strain WRSS1, have been tested in humans with considerable success. These Phase I vaccines lack the gene for the protein VirG also known as IcsA, which enables the organism to disseminate in the host target tissue. However, 5% to 20% of the vaccinated volunteers developed mild fever and brief diarrhea, and the removal of additional virulence-associated genes from the vaccine strain may reduce or eliminate these side effects. We administered 2 Shigella sonnei vaccines, WRSs2 and WRSs3, along with WRSS1 to compare their rates of colonization and clinical safety in groups of 5 rhesus macaques. The primate model provides the most physiologically relevant animal system to test the validity and efficacy of vaccine candidates. In this pilot study using a gastrointestinal model of infection, the vaccine candidates WRSs2 and WRSs3, which have additional deletions in the enterotoxin and LPS modification genes, provided better safety and comparable immunogenicity to those of WRSS1.

  10. Peracetic acid treatment generates potent inactivated oral vaccines from a broad range of culturable bacterial species

    Directory of Open Access Journals (Sweden)

    Kathrin eMoor

    2016-02-01

    Full Text Available Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principal, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency.

  11. Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

    Directory of Open Access Journals (Sweden)

    Käyhty Helena

    2003-08-01

    Full Text Available Abstract Background An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. Methods In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. Results The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC was high (1.61 μg/ml. The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. Conclusion The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines.

  12. Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.

    Science.gov (United States)

    Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban

    2011-02-24

    The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

  13. The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine

    OpenAIRE

    Dbaibo, Ghassan; Macalalad, Noel; Reyes, Mari Rose Aplasca-De Los; Dimaano, Efren; Bianco, Véronique; Baine, Yaela; Miller, Jacqueline

    2012-01-01

    Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Se...

  14. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla;

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... with a MAP protein expressed in latent infection (FET11 vaccine). FET11 vaccine proteins were formulated with CAF01 adjuvant and injected to MAP challenged calves at two different ages. 28 calves divided into two FET11 vaccine groups, a commercial vaccine and a control group were used in the study...... and followed for a year. The FET11 vaccine induced a significant T cell response against constituent vaccine proteins characterized by a high percentage of CD4+ T cells and participation of polyfunctional CD4+ T cells. Of the two different age groups, late FET11 vaccination conferred protective immunity...

  15. Properly folded bacterially expressed H1N1 hemagglutinin globular head and ectodomain vaccines protect ferrets against H1N1 pandemic influenza virus.

    Directory of Open Access Journals (Sweden)

    Surender Khurana

    Full Text Available BACKGROUND: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu". The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant technology can be used to express the hemagglutinin (HA of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330 and HA (1-480, were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330 protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330 protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480. Protein yield for the HA1 (1-330 ranged around 40 mg/Liter, while the HA (1-480 yield was 0.4-0.8 mg/Liter. CONCLUSIONS/SIGNIFICANCE: This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large

  16. Stability of vaccines - bridging from stability data to continuous safety and efficacy throughout shelf life - an always reliable approach?

    Science.gov (United States)

    Pfleiderer, Michael

    2009-11-01

    Stability studies are important tools to reliably ensure that efficacy and safety of medicinal products will remain unchanged from release of drug product until the end of shelf life. For complex medicinal products such as biological medicinal products, including vaccines, design and conduct of such studies requires particularly careful considerations in order to ensure that technical data resulting from stability studies are indeed indicative for unchanged clinical performance. Ideally, relevance of specifications controlled by stability studies as well as definition of shelf life should be justified by acceptable clinical data obtained with product at the end of the shelf life claimed.

  17. ASSESSMENT OF THE IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATIC DISEASES

    Directory of Open Access Journals (Sweden)

    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD.Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7% women and 31 (23.3% men aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA, 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group, who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia. At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT, 14 – leflunomide (LEF, and 13 – MT + tumor necrosis factor-α (TNF-α inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination. The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom.Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68% patients displayed no adverse events; 37 (28% had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4% had low-grade fever

  18. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina;

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development.......Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...

  19. [Immunological safety and sensitizing effect of an MB-7-based vaccine against hepatitis A].

    Science.gov (United States)

    Smerdova, M A; Usova, S V; Smolina, M P; Netesov, S V; Maĭdaniuk, A G; Muntianova, M A; Nemtsov, Iu V; Kriuk, N I; Iashin, V V; Karpovich, L G; Kalashnikova, T V

    2004-01-01

    The influence of a vaccine based on the MB-7 strain of hepatitis A virus (VP-MB-7) designed at the "Vector" Center of Virology and Biotechnology was studied. VP-MB-7 was found to provoke no allergic response and to have an activating effect on the specific and non-specific responses of cell and humoral immunity similar to those evoked by hepatitis A vaccine "Hep-A-in Vac".

  20. A practical approach for exploration and modeling of the design space of a bacterial vaccine cultivation process.

    Science.gov (United States)

    Streefland, M; Van Herpen, P F G; Van de Waterbeemd, B; Van der Pol, L A; Beuvery, E C; Tramper, J; Martens, D E; Toft, M

    2009-10-15

    A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged by new or additional clinical testing. Recent changes in the regulations for pharmaceutical processing allow broader ranges of process settings to be submitted for regulatory approval, the so-called process design space, which means that a manufacturer can optimize his process within the submitted ranges after the product has entered the market, which allows flexible processes. In this article, the applicability of this concept of the process design space is investigated for the cultivation process step for a vaccine against whooping cough disease. An experimental design (DoE) is applied to investigate the ranges of critical process parameters that still result in a product that meets specifications. The on-line process data, including near infrared spectroscopy, are used to build a descriptive model of the processes used in the experimental design. Finally, the data of all processes are integrated in a multivariate batch monitoring model that represents the investigated process design space. This article demonstrates how the general principles of PAT and process design space can be applied for an undefined biological product such as a whole cell vaccine. The approach chosen for model development described here, allows on line monitoring and control of cultivation batches in order to assure in real time that a process is running within the process design space.

  1. Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

    DEFF Research Database (Denmark)

    Bjoern, Jon; Iversen, Trine Zeeberg; Nitschke, Nikolaj Juul;

    2016-01-01

    BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking...... antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response....... RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded...

  2. Immunogenicity and safety of monovalent RIVM meningococcal B OMP vesicle F91 vaccine administered to children that received hexavalent meningococcal B vaccine 2.5 years ago

    NARCIS (Netherlands)

    Lafeber AB; Limpt CJP van; Berbers GAM; Labadie J; Kleijn ED de; Groot R de; Rumke HC; Alphen AJW van; Sophia Kinderziekenhuis /; LVO

    2000-01-01

    This report describes the results with respect to immunogenicity as well as reactogenicity of a monovalent P1.7h,4 OMV vaccine (MonoMen) used as booster vaccination in children previously vaccinated with a hexavalent MenB vaccine. The participants in this study were immunised in 1995-1996 with hexav

  3. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

    Directory of Open Access Journals (Sweden)

    John Lusingu

    Full Text Available The malaria vaccine candidate, RTS,S/AS01(E, showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind, randomised (1∶1 ratio controlled trial. Three doses of study or control (rabies vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E had fewer SAEs (51/447 than children in the control group (88/447. One SAE episode in a RTS,S/AS01(E recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E will become available from the Phase 3 programme.

  4. Safety and immunogenicity of a rederived, live-attenuated dengue virus vaccine in healthy adults living in Thailand: a randomized trial.

    Science.gov (United States)

    Watanaveeradej, Veerachai; Gibbons, Robert V; Simasathien, Sriluck; Nisalak, Ananda; Jarman, Richard G; Kerdpanich, Angkool; Tournay, Elodie; De La Barrerra, Rafael; Dessy, Francis; Toussaint, Jean-François; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2014-07-01

    Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial (NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.

  5. Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

    DEFF Research Database (Denmark)

    Pedersen, Court; Breindahl, Morten; Aggarwal, Naresh

    2012-01-01

    This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A......, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone....

  6. Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

    Science.gov (United States)

    Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

    2015-02-01

    The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future.

  7. BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy.

    Science.gov (United States)

    Liu, Jun; Tran, Vanessa; Leung, Andrea S; Alexander, David C; Zhu, Baoli

    2009-02-01

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG vaccine properties are largely unknown. Nevertheless, in the past decade, the development of sophisticated genome analysis techniques, coupled with advances in knowledge of the virulence mechanisms of Mycobacterium tuberculosis, have provided greater insights into the attenuation and evolution of BCG. This review article discusses these new developments, focusing on molecular mechanisms that contribute to the attenuation of BCG substrains. It is evident that BCG strains comprise natural mutants of major virulence factors of M. tb, including ESX-1, PDIM/PGL and PhoP, and that BCG substrains differ markedly in virulence level. The impacts of these findings on vaccine properties including adverse reaction effect, tuberculin reactivity and protective efficacy are discussed. These new insights have extremely important implications for national immunization programs and the development of future vaccines.

  8. 禽霍乱·新城疫二联油乳剂灭活疫苗研究(Ⅲ)——疫苗对鸭和鹅的安全性及免疫效力试验%Studies on the Inactivated Oil Emulsion Binary Vaccine against Newcastle Disease and Fowl Cholera (Ⅲ)——Safety and Immune Efficacy Test of Vaccine on Duck and Goose

    Institute of Scientific and Technical Information of China (English)

    王红琳; 杨峻; 邵华斌; 温国元; 艾地云; 罗玲; 罗青平; 张蓉蓉

    2008-01-01

    [Objective] The aim of this study is to provide theoretical basis for immunizing waterfowls (duck and goose) with the inactivated oil emulsion binary vaccine against Newcastle Disease (ND) and Fowl Cholera (FC). [Method] Bacterial liquid from solid culture media inoculated avian Pasteurella multocida (APM) type A and allantoic fluid from embryonic eggs infected with Newcastle Disease Virus (NDV) attenuated strain La Scta were mixed and inactivated by formalin to prepare 5 batches of inactivated oil emulsion binary vaccine, which were then used for the safety and immune efficacy test on duck and goose. [Result] Immunized ducks and geese didn't performed any adverse reactions in the safety test of the 5 hatches of vaccine; the immune efficacy test showed that ND-HI antibody titers of ducks and geese were no less than 4 log, three weeks after inoculation, and the protection rates against NDV and APM were 100% and 66.7% -83.3%, respectively. [Conclusion] The binary vaccine against ND and FC is safe and reliable for duck and goose, and can provide them with sufficient immunity protection against ND and FC.

  9. 预防接种安全管理的实践与探讨%Practices and Discussion on the Safety Management of Vaccination

    Institute of Scientific and Technical Information of China (English)

    万桂荣; 杜芳; 贺景云

    2012-01-01

    目的:降低预防接种风险隐患.方法:在接种流程环节中找到风险因素,有的放矢地提出针对性防护措施.结果:减少不安全接种事件的发生,提高接种质量.结论:要降低预防接种风险隐患,必须加强预防接种安全管理,严格执行预防接种操作规程,才能保证预防接种安全.%Objective: To reduce the potential risks of vaccination. Methods: To find the risk factors in the vaccination process and propose specific protective measures with target. Results: It reduced the incidence of unsafe vaccination and improved the quality of vaccination. Conclusion: To reduce the potential risks of vaccination, we must strengthen security management of vaccination, and strictly implement vaccination procedures, to ensure the safety of vaccination.

  10. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA

    Science.gov (United States)

    Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.

    2015-01-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  11. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine. PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. CONCLUSIONS: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.

  12. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP

    Science.gov (United States)

    Rampling, Tommy; Ewer, Katie J.; Bowyer, Georgina; Bliss, Carly M.; Edwards, Nick J.; Wright, Danny; Payne, Ruth O.; Venkatraman, Navin; de Barra, Eoghan; Snudden, Claudia M.; Poulton, Ian D.; de Graaf, Hans; Sukhtankar, Priya; Roberts, Rachel; Ivinson, Karen; Weltzin, Rich; Rajkumar, Bebi-Yassin; Wille-Reece, Ulrike; Lee, Cynthia K.; Ockenhouse, Christian F.; Sinden, Robert E.; Gerry, Stephen; Lawrie, Alison M.; Vekemans, Johan; Morelle, Danielle; Lievens, Marc; Ballou, Ripley W.; Cooke, Graham S.; Faust, Saul N.; Gilbert, Sarah; Hill, Adrian V. S.

    2016-01-01

    Background. The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. Method. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara–vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. Results. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. Conclusions. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. Clinical Trials Registration. NCT01883609. PMID:27307573

  13. Safety of a second dose of varicella vaccine administered at 4 to 6 years of age in healthy children in Argentina.

    Science.gov (United States)

    Fridman, Diego; Monti, Andrea; Bonnet, Marie-Claude; Armoni, Judith; Stamboulian, Daniel

    2011-10-01

    Varicela Biken [Live varicella Biken vaccine (strain Oka)] is an effective and safe vaccine for the prevention of varicella infection. Although the recommended schedule in all age groups (children, adolescents and adults) is a single dose, physicians in some countries follow the 2007 recommendation of the US Advisory Committee on Immunization Practices (ACIP) which recommends "implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12--15 months and the second dose at age 4--6 years." ( 1) Therefore, cases can arise when two doses of Varicela Biken are given even though the ACIP guidelines are a response to the US epidemiological situation and for US licensed products based on the Oka/Merck and the Oka-RIT strains (Varicela Biken is not registered in US). The aim of this study is to ascertain the safety of a second dose of Varicela Biken in children who have been previously vaccinated with the same vaccine. In this study, children, 4-6 years of age who had been previously vaccinated with Varicela Biken, received a single 0.5 mL dose of live attenuated varicella virus vaccine containing at least 1000 Plaque Forming Units (PFU) attenuated live Varicella-zoster virus (Oka strain). Participants were monitored for 30 minutes after vaccination. Predefined injection site and systemic reactions were solicited during the subsequent seven days. Unsolicited injection site reactions and unsolicited systemic events were collected throughout the study. Any serious adverse events occurring throughout the study were reported to the sponsor's pharmacovigilance department. One hundred and twenty two children were recruited and all provided safety data. There were no immediate adverse events or injection site reactions. Forty three percent of participants reported injection site reactions and 22.1% reported systemic reactions on solicitation during the seven days after vaccination. During the 30 day monitoring period, 43

  14. An overview of food safety and bacterial foodborne zoonoses in food production animals in the Caribbean region.

    Science.gov (United States)

    Guerra, Maria Manuela Mendes; de Almeida, Andre M; Willingham, Arve Lee

    2016-08-01

    Foodborne diseases (FBDs) in the Caribbean have a high economic burden. Public health and tourism concerns rise along with the increasing number of cases and outbreaks registered over the last 20 years. Salmonella spp., Shigella spp., and Campylobacter spp. are the main bacteria associated with these incidents. In spite of undertaking limited surveillance on FBD in the region, records related to bacterial foodborne zoonoses in food-producing animals and their associated epidemiologic significance are poorly documented, giving rise to concerns about the importance of the livestock, food animal product sectors, and consumption patterns. In this review, we report the available published literature over the last 20 years on selected bacterial foodborne zoonoses in the Caribbean region and also address other food safety-related aspects (e.g., FBD food attribution, importance, surveillance), mainly aiming at recognizing data gaps and identifying possible research approaches in the animal health sector.

  15. Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

    Science.gov (United States)

    Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

    2010-04-01

    This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

  16. Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.

    Science.gov (United States)

    Kobayashi, Takashi; Fukushima, Kenji; Sannan, Takanori; Saito, Noriko; Takiguchi, Yasuyuki; Sato, Yuko; Hasegawa, Hideki; Ishikawa, Koichi

    2013-04-01

    Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.

  17. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

    DEFF Research Database (Denmark)

    Lusingu, John; Olotu, Ally; Leach, Amanda

    2010-01-01

    The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant...... taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E...... reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa...

  18. A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.

    Directory of Open Access Journals (Sweden)

    Bertrand Lell

    Full Text Available BACKGROUND: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02 and a formulation based on liposomes (AS01. METHODS & PRINCIPAL FINDINGS: In this Phase II, double-blind study (NCT00307021, 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E or RTS,S/AS02(D, on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D/AS01(E of 0.88 (95% CI: 0.68-1.15 post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated. CONCLUSIONS: RTS,S/AS01(E proved similarly as well tolerated and immunogenic as RTS,S/AS02(D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan. TRIAL REGISTRATION: ClinicalTrials.gov. NCT00307021.

  19. A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Thakur, Aneesh; Aagaard, C.;

    PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen......-γ assay responses from 40 to 52 weeks compared to non-vaccinated calves. These results indicate the FET11 vaccine can be used to accelerate eradication of paratuberculosis while surveillance or test-and-manage control programs for tuberculosis and Johne’s disease remain in place. Funded by EMIDA ERA...

  20. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    Science.gov (United States)

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.

  1. Immunogenicity, Safety, and Antibody Persistence at 3, 5, and 10 Years Postvaccination in Adolescents Randomized to Booster Immunization with a Combined Tetanus, Diphtheria, 5-Component Acellular Pertussis, and Inactivated Poliomyelitis Vaccine Administered with a Hepatitis B Virus Vaccine Concurrently or 1 Month Apart

    OpenAIRE

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2014-01-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This...

  2. Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study

    Science.gov (United States)

    Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

    2016-01-01

    ABSTRACT A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain. PMID:27565435

  3. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa

    DEFF Research Database (Denmark)

    Theander, Thor Grundtvig; Lusingu, John Peter Andrea

    2015-01-01

    BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose. METHODS: From March 27, 2009, until Jan 31, 2011, childr...

  4. Community-based assessment of safety and immunogenicity of the whole cell plus recombinant B subunit (WC/rBS) oral cholera vaccine in Peru.

    Science.gov (United States)

    Begue, R E; Castellares, G; Ruiz, R; Hayashi, K E; Sanchez, J L; Gotuzzo, E; Oberst, R B; Taylor, D N; Svennerholm, A M

    1995-05-01

    Every year since its introduction in 1991, there have been epidemics of cholera in Lima, Peru. Vaccination is one approach to the control of cholera. A pilot study was conducted to assess the safety and immunogenicity of a whole cell plus recombinant B subunit (WC/rBS) cholrea vaccine in Lima, Peru. Five hundred and forty-one volunteers aged 2-65 years received two doses two weeks apart of WC/rBS vaccine or Escherichia coli K12 placebo administered in bicarbonate buffered water. Symptoms were monitored on all subjects and blood was collected from 102 persons before the first dose and two weeks after the second dose. Mild post-vaccination gastrointestinal symptoms were reported with equal frequency for both the vaccine and placebo recipients. Among 51 vaccines, 49% had a twofold or greater increase in serum vibriocidal titers (GMT = 78; range < 1:10 to 1:5120); and 92% and 82% developed a twofold or greater serum anti-cholera toxin IgG and IgA response, respectively. Persons with elevated prevaccination vibriocidal titers had a decreased response to the WC/rBS. Age and blood group did not affect the immune response. The WC/rBS vaccine was safe and immunogenic in a group of native Peruvians.

  5. Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.

    Science.gov (United States)

    Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R

    2012-01-01

    Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.

  6. Evaluation of immunogenicity and safety of Genevac B: A new recombinant hepatitis b vaccine in comparison with Engerix B and Shanvac B in healthy adults

    Directory of Open Access Journals (Sweden)

    Vijayakumar V

    2004-01-01

    Full Text Available PURPOSE: Genevac B, a new indigenous recombinant hepatitis B vaccine was evaluated for its immunogenicity and safety in comparison with Engerix B (Smithkline Beecham Biologicals, Belgium and Shanvac B (Shantha Biotechnics, India in healthy adult volunteers. METHODS: While 240 study subjects were included in the Genevac B group, 80 each were the subjects for Engerix B and Shanvac B. A three dose regimen of 0,1,2 months was adopted with 20 gm dosage uniformly in all the three groups. Vaccinees were assessed during prevaccination, followup and post vaccination periods for clinical, haematological, biochemical and immunological parameters for safety and immunogenicity. RESULTS: Successful follow-up in all parameters for four months could be achieved in 92.5% (222/240 for Genevac B study subjects and the same was 85% (68/80 and 80% (64/80 for Engerix B and Shanvac B respectively. While 100% seroconversion was observed in all the three groups, the rate of seroprotectivity was 99.5% by Genevac B, 98.5% by Engerix B and 98.4% for Shanvac B. However the difference was not statistically significant (p>0.05. The GMT values of anti HBs after one month of completion of the vaccination were 735.50, 718.23 and 662.20 mIU/mL respectively. No systemic reaction was either seen or reported by the volunteers during the vaccination process of Genevac B and other two vaccines. Clinical, haematological and biochemical safety parameters remained within normal limits throughout the study period. CONCLUSION: The study confirms that Genevac B, the new recombinant Hepatitis B vaccine has the acceptable international standards of safety and immunogenicity.

  7. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years.

    Directory of Open Access Journals (Sweden)

    Richard D Antrobus

    Full Text Available BACKGROUND: Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults. METHODS: Thirty volunteers (aged 50-85 received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8 plaque forming units (pfu. Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP and matrix protein 1 (M1 was determined by interferon-gamma (IFN-γ ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8(+ T cells, T cell receptor (TCR gene expression was evaluated using an unbiased molecular approach. RESULTS: Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4(+ and CD8(+ T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8(+ T cells, which displayed a predominant CD27(+CD45RO(+CD57(-CCR7(- phenotype both before and after vaccination. CONCLUSIONS: MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT00942071.

  8. Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid.

    Science.gov (United States)

    Kinnear, Clare L; Strugnell, Richard A

    2015-01-01

    Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

  9. Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid.

    Directory of Open Access Journals (Sweden)

    Clare L Kinnear

    Full Text Available Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.

  10. Safety and Immunogenicity of a Shigella flexneri 2a Invaplex 50 Intranasal Vaccine in Adult Volunteers

    Science.gov (United States)

    2010-06-01

    sion criteria included: specific health conditions [chronic sinusitis. chronic/seasonal rhinitis, reactive airway disease, chronic lung disease, facial ...in past 3 years). 2.3.2. Immunization procedures in humans Prior to vaccination, subjects used a facial tissue to gently clean their nasal... pattern , directed to Invaplex, LPS,IpaB, and lpaC, along with lnvaplex-specific cellular immune responses. Antigen-specific IgA responses in fecal

  11. Vaccine Basics (Smallpox)

    Science.gov (United States)

    ... this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication of Smallpox Transmission Signs and Symptoms Prevention and Treatment Smallpox Vaccine Basics Vaccine Safety Side Effects of Vaccination Who Should Get a Smallpox Vaccination? Bioterrorism The ...

  12. Efficacy of novel lipid-formulated whole bacterial cell vaccines against Mycobacterium avium subsp paratuberculosis in sheep

    NARCIS (Netherlands)

    Griffin, J.F.T.; Hughes, A.D.; Liggett, S.; Farquhar, P.A.; Mackintosh, C.G.; Bakker, D.

    2009-01-01

    Mycobacterium avium subsp. paratuberculosis [MAP], the Causative agent of enteric Johne's disease, incurs significant economic losses to the livestock industry. Prophylactic vaccination can be employed as a control means, however mineral oil-based vaccines Currently in practice have limited efficacy

  13. Cattle Immunized with a Recombinant Subunit Vaccine Formulation Exhibits a Trend towards Protection against Histophilus somni Bacterial Challenge

    Science.gov (United States)

    Madampage, Claudia Avis; Wilson, Don; Townsend, Hugh; Crockford, Gordon; Rawlyk, Neil; Dent, Donna; Evans, Brock; Van Donkersgoed, Joyce; Dorin, Craig; Potter, Andrew

    2016-01-01

    Histophilosis, a mucosal and septicemic infection of cattle is caused by the Gram negative pathogen Histophilus somni (H. somni). As existing vaccines against H. somni infection have shown to be of limited efficacy, we used a reverse vaccinology approach to identify new vaccine candidates. Three groups (B, C, D) of cattle were immunized with subunit vaccines and a control group (group A) was vaccinated with adjuvant alone. All four groups were challenged with H. somni. The results demonstrate that there was no significant difference in clinical signs, joint lesions, weight change or rectal temperature between any of the vaccinated groups (B,C,D) vs the control group A. However, the trend to protection was greatest for group C vaccinates. The group C vaccine was a pool of six recombinant proteins. Serum antibody responses determined using ELISA showed significantly higher titers for group C, with P values ranging from < 0.0148 to < 0.0002, than group A. Even though serum antibody titers in group B (5 out of 6 antigens) and group D were significantly higher compared to group A, they exerted less of a trend towards protection. In conclusion, the vaccine used in group C exhibits a trend towards protective immunity in cattle and would be a good candidate for further analysis to determine which proteins were responsible for the trend towards protection. PMID:27501390

  14. Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden.

    Science.gov (United States)

    Storsaeter, J; Olin, P; Renemar, B; Lagergård, T; Norberg, R; Romanus, V; Tiru, M

    1988-09-01

    A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.

  15. Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in healthy Brazilian infants: a randomized non-inferiority study.

    Science.gov (United States)

    de Menezes Martins, Reinaldo; Curran, Birute; Maia, Maria de Lourdes Sousa; Ribeiro, Maria das Graças Tavares; Camacho, Luiz Antonio Bastos; da Silva Freire, Marcos; Yamamura, Anna Maya Yoshida; Siqueira, Marilda Mendonça; Lemos, Maria Cristina F; de Albuquerque, Elizabeth Maciel; von Doellinger, Vanessa dos Reis; Homma, Akira; Saganic, Laura; Jarrahian, Courtney; Royals, Michael; Zehrung, Darin

    2015-03-01

    This study aimed to determine if immunogenicity to measles-mumps-rubella vaccine delivered to infants via a disposable-syringe jet injector (DSJI) was non-inferior to that administered by needle and syringe (NS). Vaccination safety was evaluated, as were the use, performance, and acceptability of each delivery method. The DSJI was the PharmaJet 2009 generation-1 device (G1) and the vaccine was measles-mumps-rubella vaccine from Bio-Manguinhos. Five hundred eighty-two healthy Brazilian infants were randomized to receive vaccine via G1 or NS. Seroconversion rates against measles and mumps viruses in the G1 treatment group did not meet non-inferiority criteria when compared with the NS group; however, responses in the G1 group to rubella virus were non-inferior to those of NS vaccinees. Most adverse events were mild or moderate. Crying after injection was more frequent in the NS group, and local skin reactions were more common in the G1 group. Five serious adverse events were judged causally unrelated to treatment and all resolved. Parents/guardians expressed a strong preference for G1 over NS for their children. Vaccinators found the G1 easy to use but noted incomplete vaccine delivery in some cases. Although the G1 has been superseded by an updated device, our results are important for the continued improvement and evaluation of DSJIs, which have the potential to overcome many of the challenges and risks associated with needle-based injections worldwide. Recommendations for future DSJI clinical studies include rigorous training of vaccinators, quantitative measurement of wetness on the skin following injection, and regular monitoring of device and vaccinator performance.

  16. DNA vaccines

    Science.gov (United States)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  17. Adenovirus 5-vectored P. falciparum vaccine expressing CSP and AMA1. Part A: safety and immunogenicity in seronegative adults.

    Directory of Open Access Journals (Sweden)

    Martha Sedegah

    Full Text Available BACKGROUND: Models of immunity to malaria indicate the importance of CD8+ T cell responses for targeting intrahepatic stages and antibodies for targeting sporozoite and blood stages. We designed a multistage adenovirus 5 (Ad5-vectored Plasmodium falciparum malaria vaccine, aiming to induce both types of responses in humans, that was tested for safety and immunogenicity in a Phase 1 dose escalation trial in Ad5-seronegative volunteers. METHODOLOGY/PRINCIPAL FINDINGS: The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP and apical membrane antigen-1 (AMA1. Group 1 (n = 6 healthy volunteers received one intramuscular injection of 2×10∧10 particle units (1×10∧10 each construct and Group 2 (n = 6 a five-fold higher dose. Transient, mild to moderate adverse events were more pronounced with the higher dose. ELISpot responses to CSP and AMA1 peaked at 1 month, were higher in the low dose (geomean CSP = 422, AMA1 = 862 spot forming cells/million than in the high dose (CSP = 154, p = 0.049, AMA1 = 423, p = 0.045 group and were still positive at 12 months in a number of volunteers. ELISpot depletion assays identified dependence on CD4+ or on both CD4+ and CD8+ T cells, with few responses dependent only on CD8+ T cells. Intracellular cytokine staining detected stronger CD8+ than CD4+ T cell IFN-γ responses (CSP p = 0.0001, AMA1 p = 0.003, but similar frequencies of multifunctional CD4+ and CD8+ T cells secreting two or more of IFN-γ, TNF-α or IL-2. Median fluorescence intensities were 7-10 fold higher in triple than single secreting cells. Antibody responses were low but trended higher in the high dose group and did not inhibit growth of cultured P. falciparum blood stage parasites. SIGNIFICANCE: As found in other trials, adenovectored vaccines appeared safe and well-tolerated at doses up to 1×10∧11 particle units. This is the first demonstration in humans of a

  18. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico

    Science.gov (United States)

    Bauer, Kristen; Esquilin, Ines O.; Cornier, Alberto Santiago; Thomas, Stephen J.; Quintero del Rio, Ana I.; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O.; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H.; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L.

    2015-01-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1–50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2–4 years], 60% [5–20 years], and 93% [21–50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. PMID:26175027

  19. Anti-bacterial and anti-toxic immunity induced by a killed whole-cell-cholera toxin B subunit cholera vaccine is essential for protection against lethal bacterial infection in mouse pulmonary cholera model.

    Science.gov (United States)

    Kang, S-S; Yang, J S; Kim, K W; Yun, C-H; Holmgren, J; Czerkinsky, C; Han, S H

    2013-07-01

    The lack of appropriate animal model for studying protective immunity has limited vaccine development against cholera. Here, we demonstrate a pulmonary cholera model conferred by intranasal administration of mice with live Vibrio cholerae. The bacterial components, but not cholera toxin, caused lethal and acute pneumonia by inducing massive inflammation. Intranasal immunization with Dukoral, comprising killed whole bacteria and recombinant cholera toxin B subunit (rCTB), developed both mucosal and systemic antibody responses with protection against the lethal challenge. Either rCTB-free Dukoral or rCTB alone partially protected the mice against the challenge. However, reconstitution of rCTB-free Dukoral with rCTB restored full protection. Parenteral immunization with Dukoral evoked strong systemic immunity without induction of mucosal immunity or protection from the challenge. These results suggest that both anti-bacterial and anti-toxic immunity are required for protection against V. cholerae-induced pneumonia, and this animal model is useful for pre-clinical evaluation of candidate cholera vaccines.

  20. Safety and protective efficacy of a spiC and crp deletion mutant of Salmonella gallinarum as a live attenuated vaccine for fowl typhoid.

    Science.gov (United States)

    Cheng, Zhao; Yin, Junlei; Kang, Xilong; Geng, Shizhong; Hu, Maozhi; Pan, Zhiming; Jiao, Xinan

    2016-08-01

    With an aim to develop a safe, immunogenic fowl typhoid (FT) vaccine, the safety and efficacy of 1009ΔspiCΔcrp, a spiC and crp deletion mutant of Salmonella gallinarum, were evaluated in chickens. Three-day-old chickens were intramuscularly immunized with 1009ΔspiCΔcrp (1×10(7)CFU) and boosted 7days later (at 10-days old) with the same dose and via the same route (vaccinated group). The vaccinated group showed no clinical symptoms and no differences in body weight compared to the unvaccinated control group. 1009ΔspiCΔcrp bacteria colonized and persisted in the liver and spleen of vaccinated chickens for >14days, and significant specific humoral and cellular immune responses were induced. Vaccinated chickens were challenged with S. gallinarum strain SG9 at 21days post-immunization (24-day-old chickens), and efficient protection was observed based on the mortality and clinical symptoms, as compared to those in the control group. These results demonstrate that 1009ΔspiCΔcrp can be used as a live attenuated vaccine.

  1. Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.

    Science.gov (United States)

    Valera, Rodrigo; García, Hilda María; Jidy, Manuel Díaz; Mirabal, Mayelin; Armesto, Marlene Isabel; Fando, Rafael; García, Luis; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Ramírez, Margarita; Bravo, Laura; Serrano, Teresita; Palma, Sara; González, Daniel; Miralles, Fernando; Medina, Vilma; Nuñez, Felicita; Plasencia, Yilian; Martínez, Juan Carlos; Mandarioti, Aleyda; Lugones, Juan; Rodríguez, Boris Luis; Moreno, Arlenis; González, Domingo; Baro, Morelia; Solis, Rosa Lidia; Sierra, Gustavo; Barbera, Ramón; Domínguez, Francisco; Gutiérrez, Carlos; Kouri, Gustavo; Campa, Concepción; Menéndez, Jorge

    2009-11-01

    A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.

  2. Safety and immunogenicity of the malaria vaccine candidate GMZ2 in malaria-exposed, adult individuals from Lambaréné, Gabon.

    Science.gov (United States)

    Mordmüller, Benjamin; Szywon, Katja; Greutelaers, Benedikt; Esen, Meral; Mewono, Ludovic; Treut, Carolin; Mürbeth, Raymund E; Chilengi, Roma; Noor, Ramadhani; Kilama, Wen L; Imoukhuede, Egeruan Babatunde; Imbault, Nathalie; Leroy, Odile; Theisen, Michael; Jepsen, Søren; Milligan, Paul; Fendel, Rolf; Kremsner, Peter G; Issifou, Saadou

    2010-09-24

    Malaria is still one of the major public health threats in sub-Saharan Africa. An effective vaccine could be a sustainable control measure that can be integrated into existing health infrastructures. The malaria vaccine candidate GMZ2 is a recombinant fusion protein of conserved parts of Plasmodium falciparum Glutamate Rich Protein and Merozoite Surface Protein 3 adjuvanted with aluminium hydroxide. GMZ2 is immunogenic and well tolerated in malaria-naive adults from Germany. To assess safety and immunogenicity in malaria-exposed individuals, 40 adults from Lambaréné, Gabon were randomly assigned to receive either 100 μg GMZ2 or a rabies control vaccine three times in monthly intervals. Both vaccines were well tolerated. One month after a full course of vaccination, GMZ2-vaccinated individuals had 1.4-fold (95% confidence interval: [1.1, 1.7]) higher baseline-corrected anti-GMZ2 antibody levels and more GMZ2-specific memory B-cells compared to the rabies group (p=0.039), despite a high prevalence of GMZ2-specific immune reactivity due to previous intense exposure to P. falciparum.

  3. An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years

    OpenAIRE

    Ambrose, Christopher S.; Yi, Tingting; Falloon, Judith

    2011-01-01

    Background Trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved in several countries for use in eligible children aged ≥2 years. Objective To describe the safety of Ann Arbor strain LAIV in children aged 2–17 years. Methods An integrated analysis of randomized, controlled trials of LAIV. Results A total of 4245 and 10 693 children received ≥1 dose of LAIV in year 1 of 6 trivalent inactivated influenza vaccine (TIV)-controlled and 14 placebo-controlled studies, res...

  4. [Safety and immunogenecity of a vaccine of polyssacharide Vi from Salmonella typhi in Cuban youths].

    Science.gov (United States)

    Azze, Rolando Felipe Ochoa; Suárez, Idalia Morelia Baró; Rodríguez, Juan Carlos Martínez; Sosa, Mayelin Mirabal; del Río, Marlene Isabel Armesto; Alvarez, Francisco Domínguez

    2003-01-01

    A randomized, controlled and double-blind study was conducted in young adults aged 18-20 aimed at evaluating the reactogenecity and immunogenecity of vaz-TyVi, a vaccine of polyssacharide Vi from Salmonella typhi. They were distributed into 3 groups: immunized with a dose of Vax-TyVi (Finlay Institute), TYPHIM Vi (Pasteur-Mérieux) or vax-TET (tetanic toxoid). Serum samples were taken before and 21 days after immunization. The immunogenecity was evaluated in 323 volunteers by an indirect ELISA. The seroconversion of those receiving vax-TyVi was 81.97% and 65.05 % for TYPHIM Vi. The postvaccine mean geometric titers were 7.41 U/mL (5.92-9.27 U/mL) and 5.41 U/mL (4.35-6.72 U/mL), respectively. The seroconversion with vax-TET was 0%. The reactogenecity of both polysaccharide vaccines was low. It was concluded that the immunogenecity of vax-TyVi was not lower than that of TYPHIM Vi and that its reactogenecity was similar.

  5. A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults.

    Science.gov (United States)

    Minassian, Angela M; Rowland, Rosalind; Beveridge, Natalie E R; Poulton, Ian D; Satti, Iman; Harris, Stephanie; Poyntz, Hazel; Hamill, Matthew; Griffiths, Kristin; Sander, Clare R; Ambrozak, David R; Price, David A; Hill, Brenna J; Casazza, Joseph P; Douek, Daniel C; Koup, Richard A; Roederer, Mario; Winston, Alan; Ross, Jonathan; Sherrard, Jackie; Rooney, Guy; Williams, Nicola; Lawrie, Alison M; Fletcher, Helen A; Pathan, Ansar A; McShane, Helen

    2011-01-01

    Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited.

  6. A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers.

    Science.gov (United States)

    Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion

    2012-03-01

    As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.

  7. Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial

    Science.gov (United States)

    Mulligan, Mark J.; Bernstein, David I.; Frey, Sharon; Winokur, Patricia; Rouphael, Nadine; Dickey, Michelle; Edupuganti, Srilatha; Spearman, Paul; Anderson, Edwin; Graham, Irene; Noah, Diana L.; Mangal, Brian; Kim, Sonnie; Hill, Heather; Whitaker, Jenifer; Emery, William; Beck, Allison; Stephens, Kathy; Hartwell, Brooke; Ogilvie, Melinda; Rimann, Nayoka; Osinski, Eileen; Destefano, Ellen; Gajadhar, Theda; Strudwick, Amanda; Pierce, Karen; Lai, Lilin; Yue, Ling; Wang, Dongli; Ying, Carl; Cline, Amy; Foltz, Tara; Wagner, Nancy; Dull, Geraldine; Pacatte, Thomas; Taggart, Barbara; Johnson, Valerie; Haller, Logan; Looney, Candi; Li, Shixiong; May, Megan; Myers, Bridgette; May, Rachel; Parker, Lawanda; Cochran, Nertaissa; Bowen, Donna; Bell, Michelle; Scoggins, Jeffery; Burns, Angela; Stablein, Claire; Wolff, Mark; Jolles, Bernadette; Leung, Brenda; Lambert, Linda; Shorer, Shy; Buchanan, Wendy; Murray, Suzanne; Chang, Soju; Gorman, Richard

    2014-01-01

    Background  Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs. Methods  A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18–49 years. Results  Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated. Conclusions  Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further. PMID:25734170

  8. Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.

    Science.gov (United States)

    Hopkins, Robert J; Kalsi, Gurdyal; Montalvo-Lugo, Victor M; Sharma, Mona; Wu, Yukun; Muse, Derek D; Sheldon, Eric A; Hampel, Frank C; Lemiale, Laurence

    2016-04-19

    AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax(®) (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥0.56) to be ≥40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine.

  9. A comparison of the oral application and injection routes using the Onderstepoort Biological Products Fowl Typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens : article

    Directory of Open Access Journals (Sweden)

    C. Purchase

    2008-05-01

    Full Text Available This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks post-vaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %, by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05 in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

  10. An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2.

    Directory of Open Access Journals (Sweden)

    Chung-Tao Tang

    Full Text Available Dengue virus (DENV, a global disease, is divided into four serotypes (DENV1-4. Cross-reactive and non-neutralizing antibodies against envelope (E protein of DENV bind to the Fcγ receptors (FcγR of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE. Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines.

  11. The adaptive response of bacterial food-borne pathogens in the environment, host and food: Implications for food safety.

    Science.gov (United States)

    Alvarez-Ordóñez, Avelino; Broussolle, Véronique; Colin, Pierre; Nguyen-The, Christophe; Prieto, Miguel

    2015-11-20

    Bacteria are constantly faced to stress situations in their ecological niches, the food and the host gastrointestinal tract. The capacity to detect and respond to surrounding changes is crucial for bacterial pathogens to survive or grow in changing environments. To this purpose, cells have evolved various sophisticated networks designed to protect against stressors or repair damage caused by them. Challenges can occur during production of foods when subjected to processing, and after food ingestion when confronted with host defensive barriers. Some pathogenic bacteria have shown the capacity to develop stable resistance against extreme conditions within a defined genomic context and a limited number of generations. On the other hand, bacteria can also respond to adverse conditions in a transient manner, through the so-called stress tolerance responses. Bacterial stress tolerance responses include both structural and physiological modifications in the cell and are mediated by complex genetic regulatory machinery. Major aspects in the adaptive response are the sensing mechanisms, the characterization of cell defensive systems, such as the operation of regulatory proteins (e.g. RpoS), the induction of homeostatic and repair systems, the synthesis of shock response proteins, and the modifications of cell membranes, particularly in their fatty acid composition and physical properties. This article reviews certain strategies used by food-borne bacteria to respond to particular stresses (acid, cold stress, extreme pressure) in a permanent or transient manner and discusses the implications that such adaptive responses pose for food safety.

  12. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

    Science.gov (United States)

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

  13. Safety, immunization coverage and determinants of a new kind of Hepatitis B vaccine firstly applied in Ningbo, China.

    Science.gov (United States)

    Yang, Sijia; Ma, Xiao; Ni, Hongxia; Zhou, Shaoying; Hu, Danbiao; Shi, Honghui; Chen, Xiaoying; Dong, Hongjun; Xu, Guozhang

    2015-01-01

    Evaluate safety and immunization coverage of a new kind of recombinant Hepatitis B vaccine (HepB) in Ningbo city, China. Two groups were carried out in 2 of 11 randomly selected countries in Ningbo in 2009. All of the infants born from July 1 to December 31, 2009 were enrolled as subjects and received 3 doses of HepB at 0, 1, 6 month. Control group (N = 3452) received current HepB derived from Saccharomyces Cerevisiae Yeast (HepB made by recombinant DNA techniques in Saccharomyces Cerevisiae Yeast, HepB-SCY; 5 μg/0.5 ml per dose) and experimental group (N = 5104) received the new kind of HepB derived from Hansenula polymorpha Yeast (HepB made by recombinant DNA techniques in Hansenula polymorpha Yeast, HepB-HPY; 10 μg/0.5 ml per dose). 3-dose and timely birth dose (TBD) coverage were available and compared between 2 groups. Standard structured questionnaires were applied to record information from parents and hospitals for selecting determinants of coverage. The data were analyzed using stepwise multiple logistic regression models. After each dose, HepB-related adverse events (AEs) and recta-temperature were recorded for 7 days. 3-dose coverage in control group (89.98%) was higher than that in experimental group (χ2 = 575.1173, P < 0.0001). TBD coverage in control and experimental group were 98.41% and 98.53%, respectively. No statistically significant difference in TBD coverage was found between 2 groups (χ2 = 0.0623, P = 0.8029). A total of 9 local AEs were reported, 4 for control group and 5 for experimental group. The percentages of subjects reporting AEs were similar across the 2 vaccination groups. No serious or immediate reactions were found in this study. From logistic models, receiving 10 μg vaccine (odds ratio [OR]:0.38; 95% confidence interval [95%CI]: 0.34-0.44) and mother migrating from other cities (OR: 0.45; 95%CI: 0.42-0.47) were the determinants for non-acceptance of 3 doses of HepB; infants born from low grade hospitals and native mothers

  14. WHO informal consultation on the application of molecular methods to assure the quality, safety and efficacy of vaccines, Geneva, Switzerland, 7-8 April 2005.

    Science.gov (United States)

    Shin, Jinho; Wood, David; Robertson, James; Minor, Philip; Peden, Keith

    2007-03-01

    In April 2005, the World Health Organization convened an informal consultation on molecular methods to assure the quality, safety and efficacy of vaccines. The consultation was attended by experts from national regulatory authorities, vaccine industry and academia. Crosscutting issues on the application of molecular methods for a number of vaccines that are currently in use or under development were presented, and specific methods for further collaborative studies were discussed and identified. The main points of recommendation from meeting participants were fourfold: (i) that molecular methods should be encouraged; (ii) that collaborative studies are needed for many methods/applications; (iii) that basic science should be promoted; and (iv) that investment for training, equipment and facilities should be encouraged.

  15. Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study

    Science.gov (United States)

    Bart, Stephan; Cannon, Kevin; Herrington, Darrell; Mills, Richard; Forleo-Neto, Eduardo; Lindert, Kelly; Abdul Mateen, Ahmed

    2016-01-01

    ABSTRACT Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (≥18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n = 1335), TIV1c (n = 676), or TIV2c (n = 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate non-inferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (≥18 – <65 y) and older (≥65 y) adults. Hemagglutinin inhibition assays were performed at days 1 and 22. Solicited local and systemic adverse events (AEs) were monitored for 7 d post-vaccination, and unsolicited AEs and serious AEs until day 181. QIVc met the non-inferiority criteria for all 4 vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B strain included in the TIV1c and TIV2c, when geometric mean titers and seroconversion rates with TIVc were compared at day 22. Between 48%–52% of subjects experienced ≥1 solicited AE, the most common being injection-site pain and headache. Serious AEs were reported by ≤1% of subjects, none were vaccine-related. The results indicate that QIVc is immunogenic and well tolerated in both younger and older adults. The immunogenicity and safety profiles of QIVc and TIVc were comparable at all ages evaluated. PMID:27322354

  16. Post-marketing safety surveillance conducted in Korea (2008–2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™)

    Science.gov (United States)

    Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

    2016-01-01

    ABSTRACT Purpose: According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). Methods: During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. Results: A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. Conclusions: We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice. PMID:27494163

  17. Immune responses and safety after dart or booster vaccination of bison with Brucella abortus strain RB51

    Science.gov (United States)

    One alternative in the Bison remote vaccination environmental impact statement (EIS) for Yellowstone National Park includes inoculation of both calves and yearlings. Although RB51 vaccination of bison does protect against experimental challenge, it was unknown whether booster vaccination might enhan...

  18. Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.

    Science.gov (United States)

    Prymula, Roman; Chlibek, Roman; Splino, Miroslav; Kaliskova, Eva; Kohl, Igor; Lommel, Patricia; Schuerman, Lode

    2008-08-18

    This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.

  19. Existing antibacterial vaccines.

    Science.gov (United States)

    Mendoza, Natalia; Ravanfar, Parisa; Satyaprakash, Anita; Satyaprakah, Anita; Pillai, Sivaprabha; Creed, Rosella

    2009-01-01

    There are countless bacterial pathogens that cause disease in humans. Many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. Vaccines allow for reduction and potential eradication of such diseases. This article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax.

  20. Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Lauren A V Orenstein

    Full Text Available BACKGROUND: Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa. METHODS: We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM, low birth weight (LBW, prematurity, and major congenital malformations (MCM in Sub-Saharan African countries were also performed. FINDINGS: Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6-73.3 per 1,000 total births, and the most common causes were hemorrhage (34%, dystocia (22%, and severe hypertensive disorders of pregnancy (22%. Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9-16.4 or premature (median 15.4%, IQR: 10.6-19.1 were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5-17.6, with the musculoskeletal system comprising 30%. INTERPRETATION: Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies

  1. Vaccines and vaccinations. The strategic issues.

    Science.gov (United States)

    Ford, R B

    2001-05-01

    The rapid proliferation of companion animal vaccines, advances in diagnostic and vaccine technology, and concerns over vaccine safety are clearly among the most important issues practicing veterinarians face as we enter the 21st century. Although many would argue that these are already issues, the future promises to be especially challenging as the vaccines we currently use and the protocols we recommend undergo unprecedented review.

  2. Randomized phase I: safety, immunogenicity and mucosal antiviral activity in young healthy women vaccinated with HIV-1 Gp41 P1 peptide on virosomes

    OpenAIRE

    Geert Leroux-Roels; Cathy Maes; Frédéric Clement; Frank van Engelenburg; Marieke van den Dobbelsteen; Michael Adler; Mario Amacker; Lucia Lopalco; Morgane Bomsel; Anick Chalifour; Sylvain Fleury

    2013-01-01

    UNLABELLED: Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring ...

  3. Improving the safety of viral DNA vaccines: development of vectors containing both 5' and 3' homologous regulatory sequences from non-viral origin.

    Science.gov (United States)

    Martinez-Lopez, A; Encinas, P; García-Valtanen, P; Gomez-Casado, E; Coll, J M; Estepa, A

    2013-04-01

    Although some DNA vaccines have proved to be very efficient in field trials, their authorisation still remains limited to a few countries. This is in part due to safety issues because most of them contain viral regulatory sequences to driving the expression of the encoded antigen. This is the case of the only DNA vaccine against a fish rhabdovirus (a negative ssRNA virus), authorised in Canada, despite the important economic losses that these viruses cause to aquaculture all over the world. In an attempt to solve this problem and using as a model a non-authorised, but efficient DNA vaccine against the fish rhabdovirus, viral haemorrhagic septicaemia virus (VHSV), we developed a plasmid construction containing regulatory sequences exclusively from fish origin. The result was an "all-fish vector", named pJAC-G, containing 5' and 3' regulatory sequences of β-acting genes from carp and zebrafish, respectively. In vitro and in vivo, pJAC-G drove a successful expression of the VHSV glycoprotein G (G), the only antigen of the virus conferring in vivo protection. Furthermore, and by means of in vitro fusion assays, it was confirmed that G protein expressed from pJAC-G was fully functional. Altogether, these results suggest that DNA vaccines containing host-homologous gene regulatory sequences might be useful for developing safer DNA vaccines, while they also might be useful for basic studies.

  4. Safety and immunogenicity of a soluble native Neospora caninum tachyzoite-extract vaccine formulated with a soy lecithin/β-glucan adjuvant in pregnant cattle.

    Science.gov (United States)

    Mansilla, Florencia Celeste; Moore, Dadín Prando; Quintana, María Eugenia; Cardoso, Nancy; Hecker, Yanina Paola; Gual, Ignacio; Czepluch, Wenzel; Odeón, Anselmo Carlos; Capozzo, Alejandra Victoria

    2015-05-15

    The global economic impact of Neospora caninum infection in cattle herds has promoted the development of vaccines that can be safely used during pregnancy. The aim of this study was to evaluate the safety and immunogenicity of a vaccine formulated with the soluble fraction of tachyzoite's lysate and a soy-based aqueous adjuvant (sNcAg/AVEC), which was protective in the mouse model and induced strong IFN-γ responses and high avidity antibodies in non-pregnant cattle. Ten pregnant heifers were vaccinated twice during the first trimester of gestation and 8 remained unvaccinated. Anti-N. caninum immune responses were efficiently primed by vaccination, evidenced by a quick induction of IgM serum titers (7dpv) and a prompt switch to high avidity IgG shortly after infection (performed at 78 or 225 days of gestation; n=5 each); while naïve cattle elicited lower IgG titers, with a delayed kinetics. High systemic IFN-γ levels were induced after infection which did not interfere with pregnancy. No local or systemic adverse effects were recorded along the study. Calves were born in term and in good health conditions, showing that the sNcAg/AVEC vaccine was safe when applied to healthy heifers during the first trimester of gestation.

  5. Immunogenicity and safety of a quadrivalent influenza vaccine in children and adolescents in Taiwan: A phase III open-label trial

    Directory of Open Access Journals (Sweden)

    Chun-Yi Lu

    2016-01-01

    Full Text Available Until recently, all seasonal influenza vaccines have been trivalent, containing strains A(H1N1, A(H3N2, and one of the two B strain lineages (Yamagata or Victoria, resulting in frequent mismatches between the circulating B strain lineage and that included in the vaccine. A quadrivalent, inactivated, split-virion influenza vaccine (IIV4 containing strains from both B lineages has been developed to address this. We performed an open-label phase III study to assess the immunogenicity and safety of the 2013–2014 Northern Hemisphere formulation of IIV4 in children and adolescents 9–17 years of age in Taiwan. Participants were vaccinated with one dose of IIV4 by intramuscular or deep subcutaneous injection. Hemagglutinin inhibition (HAI titers were measured before and 21 days after vaccination. Solicited injection-site and systemic reactions were assessed for up to 7 days after vaccination, and adverse events (AEs were recorded until day 21. One hundred participants were included. Despite relatively high pre-vaccination titers, post-vaccination HAI titers increased for all four strains, with geometric mean ratios (day 21/day 0 of 2.29 for A(H1N1, 2.05 for A(H3N2, 3.33 for B/Massachusetts (Yamagata lineage, and 4.59 for B/Brisbane (Victoria lineage. Post-vaccination seroprotection rates were 99% for A(H3N2 and 100% for A(H1N1, B/Massachusetts, and B/Brisbane. Due to high pre-vaccination titers, rates of seroconversion/significant increase of HAI titer were relatively low at 24% for A(H1N1, 20% for A(H3N2, 39% for B/Massachusetts, and 48% for B/Brisbane. Injection-site pain (56%, myalgia (45%, and malaise (15% were the most frequently reported solicited reactions, and most solicited reactions were mild or moderate. No treatment-related AEs, immediate unsolicited AEs, unsolicited non-serious injection-site AEs, grade 3 unsolicited AEs, or serious AEs were reported. In conclusion, this study showed that the 2013–2014 Northern Hemisphere

  6. Combined prime-boost vaccination against tick-borne encephalitis (TBE using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein

    Directory of Open Access Journals (Sweden)

    Zakharova LG

    2005-08-01

    Full Text Available Abstract Background Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. Results The heterologous prime-boost vaccination protocol, using a VV recombinant and bacterial plasmid, both containing the NS1 TBE virus protein gene under the control of different promoters, achieved a high level of protection in mice against lethal challenge with a highly pathogenic TBE virus strain. No signs of pronounced TBE infection were detected in the surviving animals. Conclusion Heterologous prime-boost vaccination protocols using recombinant VV and bacterial plasmids could be used for the development of flavivirus vaccines.

  7. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

    Science.gov (United States)

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

  8. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

  9. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  10. Safety and immunogenicity of human papillomavirus-16/18AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years: a phase I trial

    Institute of Scientific and Technical Information of China (English)

    Feng-Cai Zhu; Chang-Gui Li; Hong-Xing Pan; Yi-Ju Zhang; Dan Bi; Hai-Wen Tang; Sanjoy Datta

    2011-01-01

    Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection. A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples. The HPV-16/18 AS04-adjuvanted vaccine Cervarix(R)* has shown a high level of protection against HPV-16/18 infections and associated cervical lesions. This phase I trial (NCT00549900)assessed the safety, tolerability, and immunogenicity of the vaccine in Chinese. Thirty healthy Chinese females, aged 15 to 45 years with a median age of 29.5 years, received three doses of Cervarix(R) in Months 0, 1, and 6. Safety was assessed via recording solicited local and systemic symptoms within 7days and unsolicited symptoms within 30 days after each vaccination. Serious adverse events, new onset of chronic diseases, and other medically significant conditions were recorded throughout this trial. As an exploratory objective, HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7. Pain at the injection site was the most frequently reported local symptom. Two subjects reported medically significant adverse events. Both cases were assessed as unrelated to vaccination by the investigator. In Month 7, 100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers. HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females, was generally well tolerated and immunogenic, as previously shown in global studies.

  11. Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA vaccine to prevent anthrax in adults.

    Directory of Open Access Journals (Sweden)

    Bruce K Brown

    Full Text Available BACKGROUND: The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29 was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. CONCLUSIONS/SIGNIFICANCE: The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00057525.

  12. Safety evaluation and bacterial community of kung-som using PCR-DGGE technique

    Directory of Open Access Journals (Sweden)

    Sutanate Saelao

    2016-08-01

    Full Text Available This study evaluates the safety of kung-som which was distributed in local markets and using PCR-DGGE technique to identify microflora in kung-som. Lactic acid bacteria (LAB were found at counts of more than 7 log CFU g-1 in all samples and the total viable counts were about 5-8 log CFU g-1 . Bacillus cereus and yeasts were detected at around 2 log CFU g-1 and 5-6log CFU g-1, respectively. For DGGE analysis, LAB and coagulase negative staphylococci (CNS bacteria dominated over other microorganisms. The sequencing of the DNA bands from DGGE gels corresponding to kung-som samples showed the presence of LAB as the major microflora in the products, namely: Lactobacillus farciminis, Lactobacillus plantarum, Lactococcus garvieae, Tetragenococcus halophilus and Weissella thailandensis. In addition, Staphylococcus carnosus was detected in kung-som as minor microflora. These dominant strains would allow the development of defined starter cultures for improving the quality of kung-som.

  13. Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.

    Science.gov (United States)

    Soothill, Germander; Darboe, Saffiatou; Bah, Gibril; Bolarinde, Lawal; Cunnington, Aubrey; Anderson, Suzanne T

    2016-12-01

    There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015.Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5-14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib.The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA.

  14. Developing vaccines against pandemic influenza.

    OpenAIRE

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illust...

  15. 9 CFR 113.65 - Brucella Abortus Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Brucella Abortus Vaccine. 113.65... Bacterial Vaccines § 113.65 Brucella Abortus Vaccine. Brucella Abortus Vaccine shall be prepared as a desiccated live culture bacterial vaccine from smooth colonial forms of the Brucella abortus...

  16. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore.

    Science.gov (United States)

    Leo, Yee Sin; Wilder-Smith, Anneliese; Archuleta, Sophia; Shek, Lynette P; Chong, Chia-Yin; Leong, Hoe Nam; Low, Chian Yong; Oh, May-Lin Helen; Bouckenooghe, Alain; Wartel, T Anh; Crevat, Denis

    2012-09-01

    This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated viruses (CYD-TDV) and the dengue virus serotype-specific antibody responses before and 28 d after each vaccination. Participants were randomized 3:1 to receive three doses of CYD-TDV or a control vaccine at 0, 6 and 12 mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed hepatitis-A for children (aged 2-11 y) or influenza vaccine for adolescents (12-17 y) and adults (18-45 y). Between April and October 2009, 317 children, 187 adolescents and 696 adults were enrolled. In all age groups, reactogenicity was higher after the first injection of CYD-TDV than after placebo control. Reactogenicity after subsequent CYD-TDV doses was no higher than after the first dose, and tended to be lower or similar to that seen after active control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses. Post-dose 3, 66.5% of all participants were seropositive to all four serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from 43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher in children than in adolescents. These results support the continued development of CYD-TDV for the prevention of dengue disease.

  17. 国产甲型肝炎减毒活疫苗和灭活疫苗安全性评价%Evaluation on Safety of Domestic Hepatitis A Attenuated Live Vaccine and Hepatitis A Inactivated Vaccine

    Institute of Scientific and Technical Information of China (English)

    张晓曙; 安婧; 刘建锋; 付鸿; 高丽; 李慧

    2012-01-01

    Objective To evaluate safety of domestic hepatitis A attenuated live vaccine (HepA-L) and hepatitis A inactivated vaccine (HepA-I), and provide reference for emergency vaccination after hepatitis A outbreaks. Methods 493 children aged 6-9 years confirmed negative with antibody to hepatitis A virus (Anti-HAV) produced by Abbott. U.S were divided randomly into four groups. Group A were vaccinated with domestic HepA-L, group B were vaccinated with domestic HepA-I, group C were vaccinated with hepatitis B vaccine made by recombinant deoxyribonucleic acid technigues in sacchararomyces cerevisiae yeast ( HepB-SCY ) as negative control and group D were vaccinated HepA-I produced by GlaxoSmithKline Biologicals S.A. (GSK)as positive control. The adverse events following immunization (AEFIs) were observed after 30 minutes, 24, 48 and 72 hours after vaccination with double-blind method. Results The main AEFIs were fever, local pain and scleroma. There were no other severe AEFIs. The rate of AEFIs was 13.95% in Group A, 15.25% in group B, 16.80% in group C and 25.62% in group D. There were no statistical differences between different groups (x2=6.953, P=0.073). Conclusion Domestic HepA-L, domestic HepA-I and imported HepA-I are Safe.%目的 评价国产甲型病毒性肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)和灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)的安全性,为开展甲肝爆发疫情应急接种提供参考.方法 用美国雅培(Abbott)公司生产的抗甲肝病毒抗体(Antibody to Hepatitis A Virus,Anti-HAV)试剂,筛查未感染HAV的6~9岁儿童.将入选对象随机分为4组,分别接种国产HepA-L和国产HepA-I,以国产的重组乙型肝炎疫苗(酿酒酵母)(Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Technigues in Sacchararomyces Cerevisiae Yeast,HepB-SCY)为阴性对照,以GlaxoSmithKline Biologicals S.A.(GSK)生产的HepA-I为阳性对照,采取随机双盲方法,观察接种疫苗后30min

  18. Safety

    CERN Multimedia

    2003-01-01

    Please note that the safety codes A9, A10 AND A11 (ex annexes of SAPOCO/42) entitled respectively "Safety responsibilities in the divisions" "The safety policy committee (SAPOCO) and safety officers' committees" and "Administrative procedure following a serious accident or incident" are available on the web at the following URLs: Code A9: http://edms.cern.ch/document/337016/LAST_RELEASED Code A10: http://edms.cern.ch/document/337019/LAST_RELEASED Code A11: http://edms.cern.ch/document/337026/LAST_RELEASED Paper copies can also be obtained from the TIS divisional secretariat, e-mail: tis.secretariat@cern.ch. TIS Secretariat

  19. Safety and immunogenicity of Sinovac’s prototype pandemic influenza H5N1 vaccines: a review on clinical trials

    OpenAIRE

    Qiu, Yuan‐Zheng; Yin, Wei‐Dong

    2008-01-01

    Abstract  Sinovac Biotech started to develop prototype pandemic influenza H5N1 vaccines in March 2004. On 2 April 2008, Sinovac’s inactivated, aluminium‐adjuvanted, whole‐virion prototype pandemic influenza A (H5N1) vaccine (PanFlu™) was granted production licensure by the China regulatory authority State Food and Drug Administration. The whole‐virion H5N1 vaccine was manufactured in embryonated hens’ eggs using the reassortant strain NIBRG‐14 (A/Vietnam/1194/2004‐A/PR/8/34) as vaccine virus....

  20. Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Beryl A Koblin

    Full Text Available BACKGROUND: In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor. METHODOLOGY/PRINCIPAL FINDINGS: This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5 vaccine boost given at 6 months by intramuscular (IM, intradermal (ID, or subcutaneous (SC route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20. After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%. CONCLUSIONS/SIGNIFICANCE: This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing

  1. Efficacy and safety of oral tinidazole and metronidazole in treatment of bacterial vaginosis: a randomized control trial

    Directory of Open Access Journals (Sweden)

    Zahra Abbaspoor

    2014-05-01

    Full Text Available Aims: Oral metronidazole 500 mg twice a day for one week is currently the treatment of choice for bacterial vaginosis (BV. Complete treatment by this regimen takes time and occurs less often. This drug has significant side effects too. Using a drug in the shortest treatment course may increases the success of treatment. To evaluate the effectiveness and safety of oral tinidazole compare to metronidazole in treatment of BV.Methods: In this randomized, controlled, double-blind, comparative, clinical trial, 110 non-pregnant women aged between 15-45 years with confirmed diagnosis of BV by Amsels criteria were randomly assigned to receive either 2 g tinidazole tablet once daily for 2 days (n=55 or 500 mg metronidazole table twice daily for 7 days (n=55.The cure and recurrence rate were evaluated in both groups after 2 and 4 weeks follow up visits. For statistical analysis t-test,   test, fisher's exact test and Mann-Whitney test were used.Results: The results showed that cure rate after 2 weeks in tinidazole tablet group was 84.6٪ and in metronidazole group was 85.4٪ (p=0.9, and after 4 weeks recurrence rate in tinidazole and metronidazole groups was 6.9٪and 12.1٪respectively (P=0.3.Conclusions: Tinidazole table 2 g once daily for 2 days is as effective as metronidazole tablet 500 mg twice a day for 7 days in treatment of BV.

  2. Vaccines Stop Illness | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table of ... like polio and meningitis will affect their children. Vaccine Safety In light of recent questions about vaccine ...

  3. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults.

    Science.gov (United States)

    Wecker, M; Gilbert, P; Russell, N; Hural, J; Allen, M; Pensiero, M; Chulay, J; Chiu, Ya-Lin; Abdool Karim, S S; Burke, D S

    2012-10-01

    On the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped prematurely due to documentation issues with the contract manufacturer. Safety and immunogenicity were evaluated through assessments of reactogenicity, reports of adverse events, and assessment of replication-competent and Venezuelan equine encephalitis (VEE) viremia. Immunogenicity was measured using the following assays: enzyme-linked immunosorbent assay (ELISA), chromium 51 ((51)Cr)-release cytotoxic T lymphocyte (CTL), gamma interferon (IFN-γ) ELISpot, intracellular cytokine staining (ICS), and lymphoproliferation assay (LPA). Anti-vector antibodies were also measured. AVX101 was well tolerated and exhibited only modest local reactogenicity. There were 5 serious adverse events reported during the trials; none were considered related to the study vaccine. In contrast to the preclinical data, immune responses in humans were limited. Only low levels of binding antibodies and T-cell responses were seen at the highest doses. This trial also highlighted the difficulties in developing a novel vector for HIV.

  4. Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety.

    Science.gov (United States)

    Ma, Shu-Juan; Li, Xing; Xiong, Yi-Quan; Yao, A-Ling; Chen, Qing

    2015-11-01

    A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence.

  5. Safety of a Trivalent Inactivated Influenza Vaccine in Health Care Workers in Kurdistan Province, Western Iran; A Longitudinal Follow-up Study.

    Science.gov (United States)

    Soltani, Jafar; Jamil Amjadi, Mohamad

    2014-03-01

    We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines.

  6. Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone®) administered by intradermal and intramuscular route in healthy adults.

    Science.gov (United States)

    Frenck, Robert W; Belshe, Robert; Brady, Rebecca C; Winokur, Patricia L; Campbell, James D; Treanor, John; Hay, Christine M; Dekker, Cornelia L; Walter, Emmanuel B; Cate, Thomas R; Edwards, Kathryn M; Hill, Heather; Wolff, Mark; Leduc, Tom; Tornieporth, Nadia

    2011-08-05

    The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years [N=814] and 50-64 years [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard

  7. Safety and efficacy of reduced doses of Brucella melitensis strain Rev. 1 vaccine in pregnant Iranian fat-tailed ewes.

    Science.gov (United States)

    Ebrahimi, Mohammad; Nejad, Ramin Bagheri; Alamian, Saeed; Mokhberalsafa, Ladan; Abedini, Fatemeh; Ghaderi, Rainak; Jalali, Hamid Reza

    2012-01-01

    Brucellosis is one of the most important zoonotic diseases and is a significant cause of abortion in animals. Brucella melitensis strain Rev. 1 is recommended as the most effective vaccine for small ruminants but the application of full doses in adult animals is restricted. This study was conducted to determine a proper reduced dose of vaccine which confers protection but which is not abortifacient in Iranian fat-tailed sheep. A total of 51 non-vaccinated pregnant ewes were divided into three main groups and several subgroups. Ewes in different groups were vaccinated at different stages of pregnancy and various subgroups were subcutaneously immunised with different quantities of the micro-organism (7.5 × 10(6), 10(6), 5 × 10(5)). Ewes again became pregnant a year later and were challenged with the wild-type strain to evaluate the protection conferred. Results revealed that the proportion of vaccination-induced abortions was significantly higher in ewes immunised with 7.5 × 10(6) Rev. 1 organisms than in those which received 10(6) or 5 × 10(5) bacteria. While 80% of non-vaccinated ewes aborted after challenge, none of the vaccinated ewes aborted post-challenge. This study indicated that a reduced dose of Rev. 1 vaccine containing 10(6) or 5 × 10(5) live cells could be safely used to induce protection in Iranian fat-tailed sheep at various stages of pregnancy.

  8. Safety and efficacy of reduced doses of Brucella melitensis strain Rev. 1 vaccine in pregnant Iranian fat-tailed ewes

    Directory of Open Access Journals (Sweden)

    Mohammad Ebrahimi

    2012-12-01

    Full Text Available Brucellosis is one of the most important zoonotic diseases and is a significant cause of abortion in animals. Brucella melitensis strain Rev. 1 is recommended as the most effective vaccine for small ruminants but the application of full doses in adult animals is restricted. This study was conducted to determine a proper reduced dose of vaccine which confers protection but which is not abortifacient in Iranian fat-tailed sheep. A total of 51 non-vaccinated pregnant ewes were divided into three main groups and several subgroups. Ewes in different groups were vaccinated at different stages of pregnancy and various subgroups were subcutaneously immunised with different quantities of the micro-organism (7.5 × 106, 106, 5 × 105. Ewes again became pregnant a year later and were challenged with the wild-type strain to evaluate the protection conferred. Results revealed that the proportion of vaccination-induced abortions was significantly higher in ewes immunised with 7.5 × 106 Rev. 1 organisms than in those which received 106 or 5 × 105 bacteria. While 80% of non-vaccinated ewes aborted after challenge, none of the vaccinated ewes aborted post-challenge. This study indicated that a reduced dose of Rev. 1 vaccine containing 106 or 5 × 105 live cells could be safely used to induce protection in Iranian fat-tailed sheep at various stages of pregnancy.

  9. Placebo-controlled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions

    NARCIS (Netherlands)

    Horzinek, M.C.; Fehr, D.; Holznagel, E.; Bolla, S.; Hauser, B.; Herrewegh, A.A.; Lutz, Hans

    1997-01-01

    A modified live virus vaccine against feline infectious peritonitis (FIP) was evaluated in a double blind, placebo-controlled field trial in two high-risk populations. The vaccine was found to be safe and efficacious in one population of cats that had low antibody titre against feline coronavirus (F

  10. 甘草素在翘嘴鳜细菌性败血症疫苗中的佐剂效果%Adjuvant Effect of Glycyrrhizine in Vaccines against Bacterial Septicemia in Mandarinfish, Siniperca chuatsi Basilewsky

    Institute of Scientific and Technical Information of China (English)

    陈昌福; 陈晓辉; 楠田理一

    2000-01-01

    The effect of glycyrrhizine (Gly) from licorice(Glycyrrhiza glabra ) as a adjuvant in vaccines against bacterial septicemia in mandarinfish(Sinipe rca chuatsi Basilewsky) was studied. Mandarinfish were vaccinated with formalin k ill ed cells (FKC) and lipopolysaccharide (LPS) of Aeromonas hydrophila by injec tion method with or without Gly. The results showed that the phagocytic activity of leucocytes and relative percent survival (RPS) after challenge with live bacteri a in vaccinated groups with Gly were significantly higher than that in groups wi thout Gly, but after vaccination no significant differences were detected in agg lutinating antibody titers and complement activity between vaccinated groups wit h Gly and without Gly.%从甘草中提取的甘草素(Gly)添加在翘嘴鳜细菌性败血症的2种疫苗,即福尔马林灭活嗜水气单胞菌(FKC)和菌体脂多糖(LPS)中,经添加Gly的疫苗接种后,受免翘嘴鳜头肾中白细胞的吞噬活性和经活菌攻毒后的免疫保护率显著高于未添加Gly疫苗的免疫组(t 测验,P0.05).

  11. The experimental study on safety of the simultaneous immunization of anthrax vaccine and leptospira vaccine%炭疽疫苗和钩端螺旋体疫苗联合接种安全性实验研究

    Institute of Scientific and Technical Information of China (English)

    王亚玉; 邵中军; 李东力; 闫永平

    2012-01-01

    Objective An animal experiment was established to evaluate the safety of the simultaneous vaccination of anthrax vaccine and leptospira vaccine, preparing for the further use in the large population, and to find the optimal dose of simultaneous immunization for the evaluation of safety. Methods 96 mice were randomly divided into 6 groups and the number of male and female was equal. Mice were injected subcutaneously with different doses of vaccine. A combination of 1/10, 1/20, and 1/40 dose of live attenuated anthrax vaccine and 1/5 and 1/3 dose of leptospira vaccine were experimented in 5 groups and 1 group was employed as blank control. Body weight, pathology indices, biochemical indices and spontaneous activity were used to evaluate the safety of immunization. Results Local edema was the main side effect at 48~72 h after simultaneous immunization. 2 mice died in 2 groups (1,1) separately. The white blood cells (WBC) counts increased at the beginning and then became normal after the first simultaneous immunization. This phenomenon could be repeated in the later immunization. There was no significant difference in the other indexes among groups (P>0.05). Conclusions Simultaneous immunization of the optimal doses of live attenuated anthrax vaccine and leptospira vaccine on mice is practicable.%目的 对炭疽疫苗和钩端螺旋体(简称钩体)疫苗进行联合接种动物实验研究,评价联合接种疫苗的安全性,确定最佳实验免疫剂量,为炭疽疫苗和钩体疫苗的人群联合接种提供理论依据.方法 96只实验鼠分层随机分为6组,每组16只,雌雄各半.采用背部皮下接种,取炭疽疫苗1/10、钩体疫苗1/5的人用剂量进行联合接种,同时组合两种疫苗的临近剂量组,即炭疽疫苗1/20、1/40,钩体疫苗1/3的人用剂量进行联合接种,运用体重、血液学指标以及病理组织学等指标对疫苗的安全性进行评价.结果 实验动物接种2种疫苗48~72 h后,部分动物

  12. Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants.

    Science.gov (United States)

    Gatchalian, Salvacion; Yao, Yafu; Zhou, Benli; Zhang, Lei; Yoksan, Sutee; Kelly, Kim; Neuzil, Kathleen M; Yaïch, Mansour; Jacobson, Julie

    2008-04-24

    Japanese encephalitis (JE) virus is a major cause of disease, disability, and death in Asia. An effective, live, attenuated JE vaccine (LJEV) is available; however, its use in routine immunization schedules is hampered by lack of data on concomitant administration with measles vaccine (MV). This study evaluated the immunogenicity and reactogenicity of LJEV and MV when administered at the same or separate study visits in infants younger than 1 year of age. Three groups of healthy infants were randomized to receive LJEV at age of 8 months and MV at 9 months (Group 1; n=100); MV and LJEV together at 9 months (Group 2; n=236); or MV and LJEV at 9 and 10 months, respectively (Group 3; n=235). Blood was obtained 4 weeks after each vaccine administration to determine antibody levels for measles and JE. Reactogenicity was assessed by parental diaries and clinic visits. Four weeks after immunization, measles seroprotection rates (defined as > or =340 mIU/ml) were high and comparable in all three groups and specifically, rates in the combined MV-LJEV (Group 2) were not statistically inferior to those in Group 3 receiving MV separately (96% versus 100%, respectively). Likewise, the LJEV seroprotection rates were high and similar between the three groups. The reactogenicity profiles of the three vaccine schedules were also analogous. LJEV and MV administered together are well tolerated and immunogenic in infants younger than 1 year. These results should facilitate incorporation of LJEV into routine immunization schedules with MV.

  13. Alphavirus replicon vaccines.

    Science.gov (United States)

    Vander Veen, Ryan L; Harris, D L Hank; Kamrud, Kurt I

    2012-06-01

    The alphavirus replicon technology has been utilized for many years to develop vaccines for both veterinary and human applications. Many developments have been made to the replicon platform recently, resulting in improved safety and efficacy of replicon particle (RP) vaccines. This review provides a broad overview of the replicon technology and safety features of the system and discusses the current literature on RP and replicon-based vaccines.

  14. Working Group on quality, safety and efficacy of typhoid Vi capsular polysaccharide conjugate, vaccines, Jeju, Republic of Korea, 5-7 September 2012.

    Science.gov (United States)

    Jones, Chris; Lee, Chung Keel; Ahn, Chiyoung; Shin, Jinho; Knezevic, Ivana

    2013-09-23

    Typhoid fever is a gastrointestinal disease transmitted through the ingestion of contaminated water or food. The bacterium, Salmonella enterica subspecies enterica serovar Typhi is an important cause of illness and death in many poor countries where access to safe water and basic sanitation is limited. Humans are the only natural host and reservoir of S. Typhi. Typhoid fever causes around 21 million cases and at least 200,000 deaths per year. Currently, several groups are developing typhoid conjugate vaccines that are expected to be safe and effective in infancy or early childhood. The World Health Organization convened a meeting, in collaboration with the Korea Food and Drug Administration, with experts group in September 2012 to develop guidelines for regulatory evaluation of the quality, safety and efficacy of typhoid conjugate vaccines. This report summarizes collective views on scientific and technical issues that need to be considered in the guidelines.

  15. The estimation of safety booster vaccination children is more senior than 1,5 years against diphtheria, perussis, tetanus, poliomyelitis and Haemophilus influenzae type B with Pentaxim

    Directory of Open Access Journals (Sweden)

    S. M. Harit

    2009-01-01

    Full Text Available Supervision over 200 children in the age of 18–42 months (64 healthy and 136 with allergic displays, defeats CNS, often ill, and also having in the anamnesis of reaction to previous introduction DTP or Infanriks, revaccination with Pentaxim. It is shown, that 77% from them had asymptomatic current, only in 1,5% of cases strong reactions with temperature above 38,6°С were observed. Local reactions were marked at 25,5%, essentially more often at children with an allergy, defeat CNS and often ill, than at healthy (7,8%, but did not one child was not adverse events. The estimation safety vaccines Pentaxim confirms expediency of application as 1 revaccination against perussis, diphtheria, tetanus, poliomyelitis and unitary vaccination against Haemophilus influenzae type B in children are more senior than year with a various state of health.

  16. Safety and immunogenicity of a single intramuscular dose of a tetanus-diphtheria toxoid (Td) vaccine (BR-TD-1001) in healthy Korean adult subjects.

    Science.gov (United States)

    Hong, Taegon; Chung, Yong-Ju; Kim, Tae-Yeon; Kim, Ik-Hwan; Choe, Yong-Kyung; Lee, Jongtae; Jeon, Sangil; Han, Seunghoon; Yim, Dong-Seok

    2015-01-01

    BR-TD-1001 was developed as a booster for the immunity maintenance of diphtheria and tetanus. The aim of this study was to evaluate the safety and immunogenicity of BR-TD-1001 (test vaccine) in comparison with placebo and an active comparator in healthy Korean adults. A randomized, double-blind, placebo-controlled, active comparator, phase I clinical trial was conducted. Fifty subjects were randomly assigned to one of 3 treatment groups in a ratio of 2:2:1, and were administered a single intramuscular dose of test vaccine, active comparator, or placebo, respectively. All subjects were monitored for 4 weeks after injection. The antibody titers of the patients 2 and 4 weeks after vaccination were compared with the baseline. The frequencies of all adverse events including adverse drug reactions in the test group were not statistically different from those of the other treatment groups (P = 0.4974, 0.3061). No serious adverse event occurred, and no subject was withdrawn from the study for safety. The seroprotection rates against both tetanus and diphtheria at 4 weeks after vaccination were over 0.95. For anti-tetanus antibody, the geometric mean titer in the test group was significantly higher than those of the other groups (P = 0.0364, 0.0033). The geometric mean titer of anti-diphtheria antibody in the test group was significantly higher than the value of the placebo (P = 0.0347) while it was not for the value of the active comparator (P = 0.8484). In conclusion, BR-TD-1001 was safe, well-tolerated, and showed sufficient immunogenicity as a booster for diphtheria and tetanus.

  17. Safety assessment of transgenic Bacillus thuringiensis rice T1c-19 in Sprague-Dawley rats from metabonomics and bacterial profile perspectives.

    Science.gov (United States)

    Cao, Sishuo; He, Xiaoyun; Xu, Wentao; Luo, YunBo; Yuan, Yanfang; Liu, Pengfei; Cao, Bo; Shi, Hui; Huang, Kunlun

    2012-03-01

    Bacillus thuringiensis rice is facing commercialization as the main food source in the near future. The unintended effects of genetically modified (GM) organisms are the most important barriers to their promotion. We aimed to establish a new in vivo evaluation model for genetically modified foods by using metabonomics and bacterial profile approaches. T1c-19 rice flour or its transgenic parent MH63 was used at 70% wt/wt to produce diets that were fed to rats for ∼ 90 days. Urine metabolite changes were detected using (1)H NMR. Denaturing gradient gel electrophoresis and real-time polymerase chain reaction (RT-PCR) were used to detect the bacterial profiles between the two groups. The metabonomics was analyzed for metabolite changes in rat urine, when compared with the non-GM rice group, where rats were fed a GM rice diet. Several metabolites correlated with rat age and sex but not with GM rice diet. Significant biological differences were not identified between the GM rice diet and the non-GM rice diet. The bacteria related to rat urine metabolites were also discussed. The results from metabonomics and bacterial profile analyses were comparable with the results attained using the traditional method. Because metabonomics and bacterial profiling offer noninvasive, dynamic approaches for monitoring food safety, they provide a novel process for assessing the safety of GM foods.

  18. Immunity Provided by an Outer Membrane Vesicle Cholera Vaccine Is Due to O-Antigen-Specific Antibodies Inhibiting Bacterial Motility.

    Science.gov (United States)

    Wang, Zhu; Lazinski, David W; Camilli, Andrew

    2017-01-01

    An outer membrane vesicle (OMV)-based cholera vaccine is highly efficacious in preventing intestinal colonization in the suckling mouse model. Immunity from OMVs comes from immunoglobulin (Ig), particularly IgG, in the milk of mucosally immunized dams. Anti-OMV IgG renders Vibrio cholerae organisms immotile, thus they pass through the small intestine without colonizing. However, the importance of motility inhibition for protection and the mechanism by which motility is inhibited remain unclear. By using both in vitro and in vivo experiments, we found that IgG inhibits motility by specifically binding to the O-antigen of V. cholerae We demonstrate that the bivalent structure of IgG, although not required for binding to the O-antigen, is required for motility inhibition. Finally, we show using competition assays in suckling mice that inhibition of motility appears to be responsible for most, if not all, of the protection engendered by OMV vaccination, thus providing insight into the mechanism of immune protection.

  19. Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Benítez Mència

    2008-05-01

    Full Text Available Abstract Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients compared to subcutaneous administration in the control group (100 patients. Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%. Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov

  20. Occupational safety of BCG vaccine vaccination:risk factors and countermeasure%卡介苗接种的职业安全危险因素及对策

    Institute of Scientific and Technical Information of China (English)

    万正敏

    2012-01-01

    目的 揭示卡介苗接种过程中存在的职业安全危险因素,减少职业伤害风险.方法 观察接种卡介苗过程中的职业安全环节,引导医务人员在卡介苗接种各环节做好防护.结果 通过对接种过程的临床观察,提出可靠的防护方法,在接种过程中按照卡介苗接种流程操作,3年中无一例医务人员发生结核分枝杆菌感染.结论 只要从卡介苗的检查、使用、废弃空安瓿的处理过程中做好防护,对有利器损伤的医务人员及时采取预防治疗,可以防止感染结核病,防护措施值得推广.%OBJECTIVE To reveal the risk factors for the occupational safety of bacillus calmette-guerin (BCG) vaccine vaccination to reduce the risk of occupational hazard. METHODS The links of occupational safety were observed carefully during BCG vaccine inoculation procedure and the medical personnel were guide to make well protection for each link. RESULTS Through the clinical observation on inoculation procedure, a dependable protection method was put forward. And in the process of inoculating BCG vaccine according to the method, no medical personnels had tubercle rod bacteria infection in three years. CONCLUSION Once the protection is well made during the processes of check and use of BGC vaccine and the abandon of empty Ampoule Bottle, and the medical personnel who are injured by sharp instruments adopt a prevention treatment in time, the tuberculosis infection can be prevented and the protection measure is worth of promoting.

  1. A clinical trial to assess the immunogenicity and safety of Inactivated Influenza Vaccine (Whole Virion IP (Pandemic Influenza (H1N1 2009 Monovalent Vaccine; VaxiFlu-S ™ in healthy Indian adult population

    Directory of Open Access Journals (Sweden)

    A H Kubavat

    2011-01-01

    Full Text Available Background : The pandemic of H1N1 2009 influenza has spread world over and low degree of virus transmission has continued in several regions of India. Aims : To assess the immunogenicity and safety of Pandemic Influenza (H1N1 2009 Monovalent Vaccine in healthy adult Indian population. Settings and Design : Prospective, open label, multicentric, phase 2/3 clinical trial. Materials and Methods : Healthy adult Indian subjects belonging to either 18-59 years or ≥60 years age groups were enrolled and administered a single 0.5 ml (≥15 mcg of hemagglutinin antigen dose of vaccine in the deltoid muscle. Anti-hemagglutinin antibody titer was assessed at baseline and 21 (±2 days after vaccination by Hemagglutination Inhibition (HI test. Safety assessments were done for a period of 42 days. Statistical Analysis Used : Percentages of appropriate population with 95% confidence intervals calculated, log transformation of the data to calculate Geometric Mean Titers (GMTs and chi-square test and student′s t-test applied for significance testing. Results : 182/198 and 53/63 volunteers in age groups of 18-59 years and ≥60 years, respectively, achieved an HI titer ≥1 : 40 at Day 21 (91.9% [95% confidence interval: 88.1-95.7%] and 84.1% [75.1-93.2%]; P=0.072. Further, 171/198 and 50/63 volunteers in the respective age groups achieved seroconversion/four-fold increase in titer at Day 21 (86.4% [81.6-91.1%] and 79.4% [69.4-89.4%]; P=0.179. A significant rise of 22.6-fold [18.0-28.4] and 10.5-fold [7.4-15.0] was noted in GMT in the respective age groups (P<0.001 for both groups as compared to baseline. Nine vaccine-related adverse events were reported (3.4% incidence [1.2-5.6%], which were of low severity only. Conclusions : Pandemic Influenza (H1N1 2009 Monovalent Vaccine produces excellent immunogenic response with a good tolerability profile in adult Indian population.

  2. A practical approach for exploration and modeling of the design space of a bacterial vaccine cultivation process

    NARCIS (Netherlands)

    Streefland, M.; Herpen, P.F.G.; Waterbeemd, van de B.; Pol, van der L.A.; Beuvery, E.C.; Tramper, J.; Martens, D.E.; Toft, M.

    2009-01-01

    A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of t

  3. Veterinary autogenous vaccines.

    Science.gov (United States)

    Hera, A; Bures, J

    2004-01-01

    Autogenous vaccines remain a regulatory issue. They are demanded by practising veterinarians and by animal owners and they are quite widely used, mainly in Central European Countries, the Czech Republic, Hungary and Slovak Republic having probably the longest tradition with these products in Central Europe. The scope given in Article 3, Para. 2 (and/or Article 4 for some countries) of Directive 2001/82/EC applies to these products in the Acceding Countries. As these products are exempt from the harmonised regulation at the EU level, they are regulated by individual countries, the regulation varying from practically no regulatory measures in certain countries to a quite complex and demanding regulation in the other countries. Both risks and benefits are related to these products and they shall be taken into account when regulatory measures are considered. The major risks related to veterinary autogenous vaccines relate to possibility of transmission of TSE agents or other viral, bacterial and/or fungal contaminants. As appropriate and well balanced regulation of these products is deemed necessary, considering the risks related to these products, and based on the fact that national regulatory measures could be considered as a trade barrier under certain circumstances, harmonisation of the key issues or legal admission of the nationally based regulatory measures, including movement of these products from the other Member States, shall be laid down in the EU legislation. The veterinary autogenous vaccines complying with basic quality and safety requirements are thus a very useful tool in the animal health and welfare management but their use should be restricted to situations where there is no authorised veterinary medicinal product available and veterinary autogenous vaccines must not be allowed to replace good farming or veterinary practices.

  4. Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM in healthy Korean adolescents and adults

    Directory of Open Access Journals (Sweden)

    Hoan Jong Lee

    2014-11-01

    Conclusions: Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects and geometric mean titers (48, 231, 147, and 107 against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

  5. Antibacterials: A sweet vaccine

    Science.gov (United States)

    Bundle, David

    2016-03-01

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

  6. Systematic review of human papillomavirus vaccine coadministration.

    Science.gov (United States)

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  7. A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis.

    Science.gov (United States)

    Chakravarty, Jaya; Kumar, Subodh; Trivedi, Sonali; Rai, Vijay K; Singh, Anup; Ashman, Jill A; Laughlin, Elsa M; Coler, Rhea N; Kahn, Stuart J; Beckmann, Anna Marie; Cowgill, Karen D; Reed, Steven G; Sundar, Shyam; Piazza, Franco M

    2011-04-27

    Healthy Indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with Leishmania donovani based on the direct agglutination test (DAT). Three cohorts of 6 DAT-negative and 6 DAT-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 5μg, 10μg, or 20μg recombinant Leishmania polyprotein LEISH-F1 antigen+25μg MPL®-SE adjuvant). The study injections were given subcutaneously on days 0, 28, and 56, and the subjects were followed through day 168 for safety and immunological endpoints. The vaccine was safe and well-tolerated in DAT-negative and DAT-positive subjects and induced T-cell production of IFN-γ and other cytokines in response to stimulation with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani.

  8. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Directory of Open Access Journals (Sweden)

    Geert Leroux-Roels

    Full Text Available UNLABELLED: Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1. TRIAL

  9. Childhood Vaccine Schedule

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... as pneumonia, blood infections, and bacterial meningitis Rotavirus vaccine (three ... in babies and young children 4 Months DTaP, Hib, IPV, PCV, RV 6 ...

  10. Nanoparticle-detained toxins for safe and effective vaccination

    Science.gov (United States)

    Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

    2013-12-01

    Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here, we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal α-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin-mediated adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

  11. Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component.

    Directory of Open Access Journals (Sweden)

    Cindy Tamminga

    Full Text Available BACKGROUND: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge. METHODOLOGY/PRINCIPAL FINDINGS: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP. It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1 that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al. Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1 x 1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m] that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m. CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected. SIGNIFICANCE: The NMRC-MV-Ad-PfC vaccine expressing CSP was

  12. Is Systemic Lupus Erythematosus Associated With a Declined Immunogenicity and Poor Safety of Influenza Vaccination?: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Huang, Yafang; Wang, Huili; Wan, Ling; Lu, Xiaoqin; Tam, Wilson W S

    2016-05-01

    There are conflicts on whether influenza vaccinated systemic lupus erythematosus (SLE) patients are associated with a decreased immunogenicity and safety, compared with healthy controls. We conducted meta-analyses to compare SLE patients with healthy controls for flu-vaccine immunogenicity, as well as for adverse events.PubMed, MEDLINE, and Cochrane Library were searched by October 15, 2015. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality, and outcomes. The primary outcome was seroprotection (SP) rate after immunization.A total of 15 studies were included. There were significant differences in SP rates between the SLE patients and healthy controls, respectively, for H1N1 (RR 0.79, 95% CI 0.73-0.87) and B strain (RR 0.75, 95% CI 0.65-0.87), but not for H3N2 (RR 0.84, 95% CI 0.68-1.03). Subgroup analyses demonstrated SLE patients with immunosuppressants, corticosteroids, azathioprine and prednisone had significantly lower SP rates, compared with healthy controls. SLE patients with nonadjuvanted H1N1 vaccine had significantly lower SP rate, compared with healthy controls. SLE patients were not associated with increased adverse events (RR 1.88, 95% CI 0.94-3.77).SLE generates immunogenicity differently, compared with healthy controls in pandemic H1N1 and B strains, but same in seasonal H3N2 strain. Nonadjuvant and special kind of immunosuppressive biologics can play an important role in SLE immunogenicity to flu vaccine. There is no significant difference in adverse event rates between SLE patients and healthy controls.

  13. Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

    Science.gov (United States)

    Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

    2013-12-01

    The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

  14. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  15. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies

    Science.gov (United States)

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592

  16. Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: End-of-study analysis of a Phase III randomized trial

    OpenAIRE

    Einstein, Mark H.; Takacs, Peter; Chatterjee, Archana; Sperling, Rhoda S.; Chakhtoura, Nahida; Blatter, Mark M.; Lalezari, Jacob; David, Marie-Pierre; Lin, Lan; Struyf, Frank; Dubin, Gary

    2014-01-01

    The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2...

  17. Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

    Science.gov (United States)

    Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai

    2015-01-01

    A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

  18. IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS OF A TWO-YEAR FOLLOW-UP STUDY

    Directory of Open Access Journals (Sweden)

    M. S. Naumtseva

    2016-01-01

    Full Text Available Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6% women and 29 (26.4% men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD (a control group. The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32. 52 patients received methotrexate (MTX, 14 had Leflunomide (LEF, and 13 were treated with tumor necrosis factor-α (TNF-α inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination. Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom. Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level. Results and discussion. No clinical and

  19. Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy

    Directory of Open Access Journals (Sweden)

    Petra Zieglmayer

    2016-09-01

    Conclusion: The B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.

  20. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  1. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  2. Analysis of Nursing Safety Management Inoculation Effect on Vaccination Effect of Prevention in Children%儿童预防接种护理安全管理对预防接种效果的影响

    Institute of Scientific and Technical Information of China (English)

    谢超波

    2014-01-01

    Objective To investigate the effect of children's preventive nursing safety management inoculation on vaccination ef ect. 5318 cases of children immunization. Methods In our hospital from 2012 to carry out the whole safety management, with the 2011 vaccination of children were observed and compared. Results In 2012 our hospital vaccination satisfaction rate compared to 2011 increased. Conclusion Children's preventive inoculation can improve the nursing safety management of pre inoculation ef ect, improve the vaccination rate, improve the service quality of hospital vaccination.%目的探讨儿童预防接种护理安全管理对预防接种效果的影响。方法我院自2012年进行接种的5318例儿童进行全程安全管理,同2011年接种疫苗的儿童进行对比观察。结果2012年我院疫苗接种的满意率相较于2011年增加。结论儿童预防接种护理安全管理能够提高对预苗接种的效果,提高疫苗的接种率,提高医院疫苗接种的服务质量。

  3. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.

    Directory of Open Access Journals (Sweden)

    Emma-Jo Hayton

    Full Text Available TRIAL DESIGN: HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. METHODS: Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. RESULTS: Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1 and predominantly transient (<48 hours. Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range of 633 (231-1533 post-vaccination, which is of no safety concern. CONCLUSIONS: These data demonstrate

  4. Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications

    OpenAIRE

    Javier Diez-Domingo; Maurizio de Martino; Jose Garcia-Sicilia Lopez; Gian Vincenzo Zuccotti; Giancarlo Icardi; Alberto Villani; David Moreno-Perez; María Méndez Hernández; Javier Álvarez Aldeán; Ahmed Abdul Mateen; Igwebuike Enweonye; Richard de Rooij; Richa Chandra

    2016-01-01

    Background: This descriptive, non-comparative, phase III study evaluated the safety and tolerability of cell culture-derived (TIVc) and egg-derived (TIV) seasonal influenza vaccines in children at risk of influenza-related complications. Methods: Four hundred and thirty subjects were randomized 2:1 to TIVc or TIV. Subjects aged 3 to

  5. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

    Science.gov (United States)

    Greenberg, Richard N; Hurley, Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; Chaplin, Paul

    2015-01-01

    Background Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. Results The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602 PMID:26439129

  6. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

  7. Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNA-based clade C/B' HIV-1 candidate vaccine.

    Directory of Open Access Journals (Sweden)

    Sandhya Vasan

    Full Text Available BACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low, 1.0 mg (mid, and 4.0 mg (high] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0% in the placebo group, 3/12 (25% in the low-dosage group, 4/12 (33% in the mid-dosage group, and 2/12 (17% in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.

  8. Vaccination of pigs with attenuated Lawsonia intracellularis induced acute phase protein responses and primed cell-mediated immunity without reduction in bacterial shedding after challenge

    DEFF Research Database (Denmark)

    Riber, Ulla; Heegaard, Peter M. H.; Hvass, Henriette Cordes;

    2015-01-01

    nomically important diseases in modern pig production worldwide. The Enterisol®Ileitis vaccine havebeen shown to reduce clinical disease and to increase weight gain, however, while the natural infectionwith L. intracellularis can provide complete protection against re-infection, this has not been...... achievedby this vaccine. We therefore undertook a detailed characterization of immune responses to L. intracel-lularis infection in vaccinated pigs (VAC) compared to previously infected pigs (RE) in order to pinpointimmunological determinants of protection.Results: The VAC pigs shed L. intracellularis...... response was diminished and L. intracellularis specific IgG responseswere delayed and reduced compared to non-vaccinated pigs. On the other hand L. intracellularis specificIFN- responses tended to develop faster in the VAC group compared to controls.Conclusion: Although vaccinated and non-vaccinated pigs...

  9. Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: end-of-study analysis of a Phase III randomized trial.

    Science.gov (United States)

    Einstein, Mark H; Takacs, Peter; Chatterjee, Archana; Sperling, Rhoda S; Chakhtoura, Nahida; Blatter, Mark M; Lalezari, Jacob; David, Marie-Pierre; Lin, Lan; Struyf, Frank; Dubin, Gary

    2014-01-01

    The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.

  10. A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children.

    Directory of Open Access Journals (Sweden)

    Tinh Hien Tran

    Full Text Available BACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-ssaV(- ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. OBJECTIVES: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. METHODS: Subjects were randomly assigned to receive either a nominal dose of 5x10(9 CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS specific serum IgA and IgG ELISA. PRINCIPAL FINDINGS: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5% of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36% of 50 subjects in the placebo group (odds ratio (OR [95%CI] = 1.23 [0.550-2.747]; p = 0.691. Faecal shedding of S. Typhi (Ty2 aroC(-ssaV(- ZH9 was detected in 51 (51%; 95% CI, 41-61% of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change in LPS specific serum IgG (day 14 or 28 and/or 50% increase (1.5 fold change in LPS specific serum IgA (day 7 or 14 from baseline was detected in 98 (97%; 95% CI, 92-99% of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29% of 50 placebo

  11. Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in India: A randomized, observer-blind, placebo-controlled phase II trial.

    Science.gov (United States)

    Dubey, Anand Prakash; Agarkhedkar, Sharad; Chhatwal, Jugesh; Narayan, Arun; Ganguly, Satyabrata; Wartel, T Anh; Bouckenooghe, Alain; Menezes, Josemund

    2016-01-01

    Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.

  12. Tuberculosis vaccine types and timings.

    Science.gov (United States)

    Orme, Ian M

    2015-03-01

    Traditionally, the design of new vaccines directed against Mycobacterium tuberculosis, the most successful bacterial pathogen on the planet, has focused on prophylactic candidates that would be given to individuals while they are still young. It is becoming more apparent, however, that there are several types of vaccine candidates now under development that could be used under various conditions. Thus, in addition to prophylactic vaccines, such as recombinant Mycobacterium bovis BCG or BCG-boosting vaccines, other applications include vaccines that could prevent infection, vaccines that could be given in emergency situations as postexposure vaccines, vaccines that could be used to facilitate chemotherapy, and vaccines that could be used to reduce or prevent relapse and reactivation disease. These approaches are discussed here, including the type of immunity we are trying to specifically target, as well as the limitations of these approaches.

  13. Novel transgenic rice-based vaccines.

    Science.gov (United States)

    Azegami, Tatsuhiko; Itoh, Hiroshi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-04-01

    Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines.

  14. Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.

    Science.gov (United States)

    Denny, Lynette; Hendricks, Bronwyn; Gordon, Chivaugn; Thomas, Florence; Hezareh, Marjan; Dobbelaere, Kurt; Durand, Christelle; Hervé, Caroline; Descamps, Dominique

    2013-11-19

    In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339.

  15. Evaluation of immunogenicity and safety of the new tetanus-reduced diphtheria (Td) vaccines (GC1107) in healthy Korean adolescents: a phase II, double-blind, randomized, multicenter clinical trial.

    Science.gov (United States)

    Rhim, Jung-Woo; Lee, Kyung-Yil; Kim, Sang-Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Kim, Hwang Min; Choi, Young-Youn; Ma, Sang-Hyuk; Kim, Dong-Ho; Ahn, Dong Ho; Kang, Jin-Han

    2013-04-01

    This phase II clinical trial was conducted to compare the immunogenicity and safety of a newly developed tetanus-reduced diphtheria (Td) vaccine (GC1107-T5.0 and GC1107-T7.5) and control vaccine. This study was also performed to select the proper dose of tetanus toxoid in the new Td vaccines. Healthy adolescents aged between 11 and 12 yr participated in this study. A total of 130 subjects (44 GC1107-T5.0, 42 GC1107-T7.5 and 44 control vaccine) completed a single dose of vaccination. Blood samples were collected from the subjects before and 4 weeks after the vaccination. In this study, all subjects (100%) in both GC1107-T5.0 and GC1107-T7.5 groups showed seroprotective antibody levels (≥ 0.1 U/mL) against diphtheria or tetanus toxoids. After the vaccination, the geometric mean titer (GMT) against diphtheria was significantly higher in Group GC1107-T5.0 (6.53) and GC1107-T7.5 (6.11) than in the control group (3.96). The GMT against tetanus was 18.6 in Group GC1107-T5.0, 19.94 in GC1107-T7.5 and 19.01 in the control group after the vaccination. In this study, the rates of local adverse reactions were 67.3% and 59.1% in GC1107-T5.0 and GC1107-7.5, respectively. No significant differences in the number of adverse reactions, prevalence and degree of severity of the solicited and unsolicited adverse reactions were observed among the three groups. Thus, both newly developed Td vaccines appear to be safe and show good immunogenicity. GC1107-T5.0, which contains relatively small amounts of tetanus toxoid, has been selected for a phase III clinical trial.

  16. Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST evaluating the human-bovine (WC3 reassortant pentavalent rotavirus vaccine (RV5

    Directory of Open Access Journals (Sweden)

    Van Damme Pierre

    2010-06-01

    Full Text Available Abstract Background The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5 including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE. The per-protocol (PP analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. Methods Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. Results In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED visits 88.9% (95% CI: 84.9, 91.9 for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6 reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5 and 95.9% (95% CI: 92.2, 97.8 among parents contacted every 2 weeks (number evaluable = 4,451 and every 6 weeks (number evaluable = 52,683 respectively. Conclusions Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations

  17. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers.

    Science.gov (United States)

    Hopkins, Robert J; Daczkowski, Nancy F; Kaptur, Paulina E; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L; Bernton, Edward

    2013-06-26

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax(®) (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18-50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA+0.5mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA+0.25mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA+0.5mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA+0.25mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909.

  18. Phase 1 safety and immunogenicity evaluation of ADMVA, a multigenic, modified vaccinia Ankara-HIV-1 B'/C candidate vaccine.

    Directory of Open Access Journals (Sweden)

    Sandhya Vasan

    Full Text Available BACKGROUND: We conducted a Phase I dose-escalation trial of ADMVA, a Clade-B'/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADMVA or placebo was administered intramuscularly at months 0, 1 and 6 to 50 healthy adult volunteers not at high risk for HIV-1. In each dosage group [1x10(7 (low, 5x10(7 (mid, or 2.5x10(8 pfu (high] volunteers were randomized in a 3:1 ratio to receive ADMVA or placebo in a double-blinded design. Subjects were followed for local and systemic reactogenicity, adverse events including cardiac adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA, immunoflourescent staining, and HIV-1 neutralization. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. Anti-vaccinia binding titers were measured by ELISA. ADMVA was generally well-tolerated, with no vaccine-related serious adverse events or cardiac adverse events. Local or systemic reactogenicity events were reported by 77% and 78% of volunteers, respectively. The majority of events were of mild intensity. The IFNgamma ELISpot response rate to any HIV antigen was 0/12 (0% in the placebo group, 3/12 (25% in the low dosage group, 6/12 (50% in the mid dosage group, and 8/13 (62% in the high dosage group. Responses were often multigenic and occasionally persisted up to one year post vaccination. Antibodies to gp120 were detected in 0/12 (0%, 8/13 (62%, 6/12 (50% and 10/13 (77% in the placebo, low, mid, and high dosage groups, respectively. Antibodies persisted up to 12 months after vaccination, with a trend toward agreement

  19. Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Jeffrey R Currier

    Full Text Available BACKGROUND: We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand. METHODOLOGY/PRINCIPAL FINDINGS: MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7 or 10(8 pfu or intradermally (ID; 10(6 or 10(7 pfu at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10∶2. Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFNγ Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a (51Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i moderate in magnitude (median IFNγ Elispot of 78 SFC/10(6 PBMC at 10(8 pfu IM, but high in response rate (70% (51Cr-release positive; 90% Elispot positive; 100% ICS positive, at 10(8 pfu IM; (ii predominantly HIV Env-specific CD4(+ T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route; (iv dose- and route-dependent with 10(8 pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 10(8 pfu IM. CONCLUSIONS/SIGNIFICANCE: MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and

  20. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  1. Safety evaluation of a quadrivalent split influenza vaccine%四价流感病毒裂解疫苗的安全性研究

    Institute of Scientific and Technical Information of China (English)

    吴虓飞; 金鑫; 胡宇驰; 吕晶

    2014-01-01

    Objective To evaluate muscular stimulation,acute toxicity and anaphylaxis of a quadrivalent split influenza vaccine for safety investigation.Methods Rabbits were intramuscularly administrated with the vaccine (0.5 ml,once daily for consecutive 2 d).Macrographic and pathological examinations of injection site were conducted 48 h and 16 d after the last administration.Mice were intramuscularly injected with the vaccine (0.2 ml) and observed continuously for 14 d for acute toxical symptoms.Guinea pigs were intramuscularly administrated with the vaccine (0.5 ml) every other day for 3 times and intravenously injected (1.0 ml) 14 and 21 d after the last sensitization,and then allergic reactions were observed within 30 min.Results The vaccine had no intramuscular irritation or injury effect on the injection site 48 h and 16 d after administration.All mice survived and no toxicological changes were observed in body weight,feed consumption,injection sites,appearance,behavioral activity,respiration,excretion,macroscopic examination of organs and tissues.No allergy symptoms occurred in guinea pigs after intravenous injection.Conclusion There is no intramuscular stimulation,acute toxicity and sensitization of the quadrivalent split influenza vaccine.%目的 对四价流感病毒裂解疫苗进行肌肉刺激性、急性毒性和过敏性评价,以考察其安全性.方法 对家兔后肢股四头肌肌肉注射0.5 ml四价流感病毒裂解疫苗,每天接种1次,连续接种2d,末次接种后48 h和16d对注射部位进行肉眼和病理组织学检查.对小鼠后肢肌肉注射0.2 ml疫苗后,连续4h和14d观察各种不良反应.豚鼠后肢隔天肌肉注射0.5 ml疫苗,共接种致敏3次,分别于末次接种后14和21 d静脉注射1.0 ml疫苗进行激发,观察豚鼠30 min内是否出现过敏反应.结果 家兔在末次接种后48 h和16 d,未观察到明显的局部刺激作用.小鼠接种后全部存活,摄食量和体重指标正常,注射部位肌肉、外观

  2. Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18-25 years: event-triggered analysis of a randomized controlled trial.

    Science.gov (United States)

    Zhu, Feng-Cai; Hu, Shang-Ying; Hong, Ying; Hu, Yue-Mei; Zhang, Xun; Zhang, Yi-Ju; Pan, Qin-Jing; Zhang, Wen-Hua; Zhao, Fang-Hui; Zhang, Cheng-Fu; Yang, Xiaoping; Yu, Jia-Xi; Zhu, Jiahong; Zhu, Yejiang; Chen, Feng; Zhang, Qian; Wang, Hong; Wang, Changrong; Bi, Jun; Xue, Shiyin; Shen, Lingling; Zhang, Yan-Shu; He, Yunkun; Tang, Haiwen; Karkada, Naveen; Suryakiran, Pemmaraju; Bi, Dan; Struyf, Frank

    2017-01-01

    We previously reported the results of a phase II/III, double-blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7-99.9) HPV-16/18 AS04-adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6-month (M) persistent infection (PI) with a mean follow-up of HPV-16/18 vaccine or Al(OH)3 (control) at M0, 1, 6. VE against HPV-16/18-associated CIN2+, and cross-protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according-to-protocol efficacy cohort, in initially seronegative/DNA-negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV-16/18-associated CIN2+ was 87.3% (5.3-99.7); VE against incident infection or against 6-month persistent infection associated with HPV-31/33/45 was 50.1% (34.3-62.3) or 52.6% (24.5-70.9), respectively. At least, 99.6% of HPV-16/18-vaccines remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and -18 geometric mean titers were 1271.1 EU/mL (1135.8-1422.6) and 710.0 EU/ml (628.6-801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination-related (blinded data). VE against HPV-16/18-associated CIN2+ was demonstrated and evidence of cross-protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.

  3. Safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in adolescents aged 12-15 years: Interim analysis of a large community-randomized controlled trial.

    Science.gov (United States)

    Lehtinen, Matti; Eriksson, Tiina; Apter, Dan; Hokkanen, Mari; Natunen, Kari; Paavonen, Jorma; Pukkala, Eero; Angelo, Maria-Genalin; Zima, Julia; David, Marie-Pierre; Datta, Sanjoy; Bi, Dan; Struyf, Frank; Dubin, Gary

    2016-12-01

    This community-randomized controlled trial was initiated to assess the overall and herd effects of 2 different human papillomavirus (HPV) immunization strategies in over 80,000 girls and boys aged 12-15 y in 33 communities in Finland (ClinicalTrials.gov NCT00534638). Overall, 14,838 adolescents received HPV-16/18 vaccine (2,440 boys and 12,398 girls) and 17,338 received hepatitis-B virus (HBV) vaccine (9,221 boys and 8,117 girls). In an interim analysis, vaccine safety was assessed by active monitoring and surveillance via health registry linkage. Active monitoring showed that the HPV-16/18 vaccine has acceptable safety and reactogenicity in boys. In all study participants, the observed incidences (per 100,000 person-years) of serious adverse events (SAEs) possibly related to vaccination were 54.3 (95% Confidence Interval [CI]: 34.0-82.1) in the HPV-16/18 group and 64.0 (95% CI: 43.2-91.3) in the HBV group. During the follow-up period for this interim analysis, the most common new-onset autoimmune diseases (NOADs; with incidence rate ≥15 per 100,000) in any group based on hospital discharge registry (HILMO) download were ulcerative colitis, juvenile arthritis, celiac disease, insulin-dependent diabetes mellitus (IDDM) and Crohn's disease. No increased NOAD incidences were observed in HPV-16/18 vaccine recipients compared to HBV vaccine recipients. In both the SAE possibly related- and HILMO-analyses, a lower incidence of IDDM was observed in HPV-16/18 vaccinees compared to HBV vaccinees (relative risks, 0.26 [95% CI: 0.03-1.24] and 0.16 [95% CI: 0.03-0.55], respectively).

  4. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants

    Science.gov (United States)

    Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa

    2017-01-01

    ABSTRACT We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2–3–4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18–24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1–3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile. PMID:27768515

  5. Emerging Vaccine Informatics

    Directory of Open Access Journals (Sweden)

    Yongqun He

    2010-01-01

    Full Text Available Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO has been initiated to integrate various vaccine data and support automated reasoning.

  6. Safety and immunogenicity of escalating dosages of a single oral administration of peru-15 pCTB, a candidate live, attenuated vaccine against enterotoxigenic Escherichia coli and Vibrio cholerae.

    Science.gov (United States)

    Chen, Wilbur H; Garza, Jose; Choquette, Monique; Hawkins, Jennifer; Hoeper, Amy; Bernstein, David I; Cohen, Mitchell B

    2015-01-01

    Enterotoxigenic Escherichia coli (ETEC) organisms are a leading cause of infectious diarrhea in developing countries. A live, attenuated cholera strain that expresses high levels of the nontoxic B subunit of cholera toxin, which might also serve as an ETEC protective antigen, was evaluated for safety, excretion, and immunogenicity in healthy volunteers. We enrolled four inpatient dose-escalation cohorts of 15 to 16 eligible subjects to randomly (3:1) receive a single oral dose of vaccine or placebo (buffer alone), evaluating 1 ×10(7), 1 ×10(8), 1 ×10(9), and 1 ×10(10) CFU of the vaccine. The vaccine was well tolerated, although some subjects experienced moderate diarrhea. The serum Inaba vibriocidal antibody response appeared to display a dose-response relationship with increasing dosages of vaccine, plateauing at the 10(9)-CFU dosage. The serum antitoxin (cholera toxin and heat-labile enterotoxin) antibody seroconversion rate (4-fold increase over baseline) also appeared to display a dose-response relationship. The vaccine strain was excreted in stool cultures, displaying a dose-response relationship. A single oral dose of Peru-15 pCTB at dosages up to 1 ×10(10) CFU was safe and immunogenic in this first-in-human trial. These encouraging data support the ongoing clinical development of this candidate combined cholera and ETEC vaccine. (This study has been registered at ClinicalTrials.gov under registration no. NCT00654108.).

  7. IMMUNOGENICITY AND SAFETY OF QUINVAXEM® (DIPHTHERIA, TETANUS, WHOLE-CELL PERTUSSIS, HEPATITIS B AND HAEMOPHILUS INFLUENZAE TYPE B VACCINE) GIVEN TO VIETNAMESE INFANTS AT 2 TO 4 MONTHS OF AGE.

    Science.gov (United States)

    Huu, Tran Ngoc; Phuong, Nguyen Thi Minh; Toan, Nguyen Trong; Thang, Ho Vinh

    2015-07-01

    Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem® vaccine in children. A total of 131 infants received the Quinvaxem® vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP ≥ 0.15 µg/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP ≥ 0.15 µg/ml). The Quinvaxem® vaccine was well tolerated and has a low rate of adverse events. Quinvaxem® given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam.

  8. A game dynamic model for vaccine skeptics and vaccine believers: measles as an example.

    Science.gov (United States)

    Shim, Eunha; Grefenstette, John J; Albert, Steven M; Cakouros, Brigid E; Burke, Donald S

    2012-02-21

    Widespread avoidance of Measles-Mumps-Rubella vaccination (MMR), with a consequent increase in the incidence of major measles outbreaks, demonstrates that the effectiveness of vaccination programs can be thwarted by the public misperceptions of vaccine risk. By coupling game theory and epidemic models, we examine vaccination choice among populations stratified into two behavioral groups: vaccine skeptics and vaccine believers. The two behavioral groups are assumed to be heterogeneous with respect to their perceptions of vaccine and infection risks. We demonstrate that the pursuit of self-interest among vaccine skeptics often leads to vaccination levels that are suboptimal for a population, even if complete coverage is achieved among vaccine believers. The demand for measles vaccine across populations driven by individual self-interest was found to be more sensitive to the proportion of vaccine skeptics than to the extent to which vaccine skeptics misperceive the risk of vaccine. Furthermore, as the number of vaccine skeptics increases, the probability of infection among vaccine skeptics increases initially, but it decreases once the vaccine skeptics begin receiving the vaccination, if both behavioral groups are vaccinated according to individual self-interest. Our results show that the discrepancy between the coverages of measles vaccine that are driven by self-interest and those driven by population interest becomes larger when the cost of vaccination increases. This research illustrates the importance of public education on vaccine safety and infection risk in order to maintain vaccination levels that are sufficient to maintain herd immunity.

  9. Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02D malaria vaccine in infants living in a malaria-endemic region

    Directory of Open Access Journals (Sweden)

    Abdulla Salim

    2013-01-01

    Full Text Available Abstract Background The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02D vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. Methods This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02D or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. Results From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02D (33.5%; 95% confidence interval [CI]: 26.5, 41.2 and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2. The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02D and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02D and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02D group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072 and 26.7% (95% CI: -33.1 to 59.6, p = 0.307 over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20

  10. Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

    Science.gov (United States)

    Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

    2015-09-01

    For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised.

  11. Safety and Efficacy of an Attenuated Infectious Bovine Rhinotracheitis Virus Vaccine%牛传染性鼻气管炎活疫苗安全性和免疫保护效果研究

    Institute of Scientific and Technical Information of China (English)

    冷雪; 郭利; 张淑琴; 武华

    2011-01-01

    The attenuated infectious bovine rhinotracheitis virus (IBRV) vaccine was tested for its safety and efficacy in host animals. In order to test the safety of the vaccine,one-month-old calves,6 to 8 month old calves,and heifers were inoculated with 2 mL (10 doses) of the vaccine. In the efficacy study,6 to 8 month old calves were vaccinated with single dose 1 mL of the vaccine. Then, the animals were challenged with a virulent challenge virus on 28 days post vaccination for immunogenicity of the vaccine. The results revealed that the calves of different ages did not show any clinical diseases post-vaccination. The newborn calves are normal and healthy,and no abortion,stillbirth or mummy fetus occurred in the pregnant cows. Immunogenicity study demonstrated that the vaccine provided five fifths protection to calves against the IBRV infection and clinical diseases caused by the challenge. The results indicated that the vaccine is safe and have a good efficacy to host animals.%本试验使用牛传染性鼻气管炎弱毒活疫苗进行安全性和免疫保护效果研究,将该疫苗分别接种1月龄犊牛、6~8月龄牛及后备母牛,接种剂量为2mL(10头份),检验疫苗安全性.将疫苗接种6~8月龄牛,接种剂量为1 mL(1头份),疫苗接种后28 d使用检验用强毒进行攻毒,检验疫苗对攻击用强毒的保护效力.结果表明,不同月龄牛接种疫苗后体温正常,无任何临床可见异常,后备母牛接种疫苗后精神状态及食欲均良好,无流产、死胎及木乃伊胎出现.疫苗接种牛对强毒攻击可产生较好的抵抗力,攻毒保护率达5/5.研究结果表明,该疫苗对牛安全,且免疫保护效果良好.

  12. Safety, immunogenicity and cross-reactivity of a Northern hemisphere 2013–2014 seasonal trivalent inactivated split influenza virus vaccine, Anflu®

    Science.gov (United States)

    Shen, Yonggang; Hu, Yuansheng; Meng, Fanya; Du, Wenjun; Li, Wei; Song, Yufei; Ji, Xiaoci; Huo, Liqun; Fu, Zhenping; Yin, Weidong

    2016-01-01

    ABSTRACT Anflu® is a seasonal trivalent inactivated split-virion influenza vaccine manufactured by Sinovac Biotech Co., Ltd. The objectives of this study were to evaluate the safety of Anflu® (2013–14 formulation: H1N1, H3N2 and BYAM) in infants and adults and its immunogenicity and cross-reactivity against mismatched influenza B lineage and avian influenza A(H7N9) viruses (hereafter BVIC and H7N9, respectively) in adults. In this phase IV open label trial, infants 6–35 months old (n=61) each received two injections with 28 days apart; adults 18–60 yrs old (n=60) and elderly >60 yrs old (n=61) each received one injection. Information of adverse events was collected through safety observation and follow-up visits. Pre- and post-immune blood samples (day 0 and 21) were collected from subjects ≥18 yrs old to detect hemagglutination inhibition antibody titers and calculate seroprotection rates (SPRs) and seroconversion rates (SCRs). The overall adverse reaction incidence was 1.6% (3/182), and no serious adverse event was reported during the study period. For subjects ≥18 yrs old, the SCRs, SPRs, and the geometric mean titers (GMTs) met the European criteria for all three strains. In addition, the point estimations of SCR, SPR and GMT for BVIC also met the European criteria. Six subjects were seroconverted against H7N9; however the serological results did not meet the European criteria. In conclusion, the results showed a satisfactory safety and immunogenicity profile of Anflu® and cross-reactivity against BVIC, but did not demonstrate cross-reactivity against H7N9 (Clinicaltrials.gov ID: NCT02269852). PMID:26934750

  13. Thermostable cross-protective subunit vaccine against Brucella species.

    Science.gov (United States)

    Cherwonogrodzky, John W; Barabé, Nicole D; Grigat, Michelle L; Lee, William E; Poirier, Robert T; Jager, Scott J; Berger, Bradley J

    2014-12-01

    A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation.

  14. Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant : Safety and Tolerability

    NARCIS (Netherlands)

    Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

    2016-01-01

    BACKGROUND AND OBJECTIVES: QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Mat

  15. Safety and immunogenicity of a delta inulin-adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals.

    Science.gov (United States)

    Bielefeldt-Ohmann, Helle; Prow, Natalie A; Wang, Wenqi; Tan, Cindy S E; Coyle, Mitchell; Douma, Alysha; Hobson-Peters, Jody; Kidd, Lisa; Hall, Roy A; Petrovsky, Nikolai

    2014-12-17

    In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74-152 days old, received two injections of JE-ADVAX™. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAX™ was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAX™ at 36-83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAX™ booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAX™ appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.

  16. Vaccines and autism: evidence does not support a causal association.

    Science.gov (United States)

    DeStefano, F

    2007-12-01

    A suggested association between certain childhood vaccines and autism has been one of the most contentious vaccine safety controversies in recent years. Despite compelling scientific evidence against a causal association, many parents and parent advocacy groups continue to suspect that vaccines, particularly measles-mumps-rubella (MMR) vaccine and thimerosal-containing vaccines (TCVs), can cause autism.

  17. 甲型H1N1流行性感冒疫苗接种安全性研究%The Study on Safety of Influenza A (H1N1) Vaccination

    Institute of Scientific and Technical Information of China (English)

    张国民; 武文娣; 李克莉; 刘大卫; 杨忠东; 肖奇友; 王华庆; 张振国; 张晓曙; 黄卓英; 疏俊; 李顺利; 赵占杰; 杨宏; 许涤沙

    2012-01-01

    目的 分析评价甲型H1N1流行性感冒(流感)(甲流)疫苗上市后大规模接种的安全性.方法 对接种甲流疫苗人群和接种季节性流感疫苗(Seasonal Influenza Vaccine,sInfV)人群开展主动监测与常规监测相结合的方式进行疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)监测.结果 在18853名接种甲流疫苗人群中发生一般反应353例,发生率为18723.81/100万剂;异常反应16例,发生率为848.67/100万剂;偶合症2例.在17012名接种sInfV人群中,发生一般反应181例,发生率为10639.55/100万剂,异常反应1例,发生率为58.78/100万剂.接种甲流疫苗的一般反应(x2=39.85,P<0.001)与异常反应(x2=11.78,P<0.001)报告发生率均高于sInfV,差异有统计学意义.结论 我国的甲流疫苗的安全性良好.%Objective This study is to obtain the safety evidence of influenza A (H1N1) in a large scale vaccination practice. Method based on the national adverse events following immunization (AEFI) surveillance system, a passive searching for the AEFI after influenza A (H1N1) vaccination was carried out. Results Among 18,853 individuals vaccinated influenza A(H1N1) vaccine, 353 common, minor reactions (reporting rate, 18,723.81 per 1,000,000 vaccinated) and 16 rare, serious reaction (reporting rate, 848.67 per 1,000,000 vaccinated)and 2 coincidental illness were reported. Among 17,012 individuals vaccinated seasonal influenza vaccine, 181 common, minor reactions (reporting rate, 10,639.55 per 1,000,000 vaccinated) and 1 rare, serious reaction were reported. Compared with the seasonal influenza vaccine group, the influenza A(H1N1) vaccinated group were reported more cases with common, minor reactions and rare, serious reaction after vaccination. The difference has significant statistics between slnfV and Influenza A ((H1N1) vaccine. Conclusion The safety of Influenza A (H1N1) vaccine is good.

  18. [Efficacy and safety of clavulanic acid/amoxicillin (1: 14) dry syrup in the treatment of children with acute bacterial rhinosinusitis].

    Science.gov (United States)

    Sugita, Rinya; Yamamoto, Shuichi; Motoyama, Hidekatsu; Yarita, Masao

    2015-06-01

    To demonstrate clinical value of clavulanic acid/amoxicillin (CVA/AMPC) 1:14 combination dry syrup for acute bacterial rhinosinusitis (ABRS), the efficacy and safety were evaluated in a multicenter, open-label, uncontrolled study in 27 children with ABRS. The proportion of subjects who were 'cured' at the test of cure as the primary endpoint was 88.5%. In subjects with a major pathogenic bacteria at baseline (i.e., Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) bacterial eradication was achieved in ≥ 80% of the subjects with the exception of β-lactamase non-producing ampicillin resistant H. influenzae: BLNAR and β-lactamase producing ampicillin resistant H. influenzae: BLPAR (β-lactamase producing amoxicillin/clavulanic acid resistant H. influenzae: BLPACR). The MIC of CVA/AMPC (1:14) was not higher than 4 μg/mL for all pathogens except one strain each of BLNAR and BLPAR (BLPACR). Drug-related adverse events were reported in 19% of patients (5/27 patients). All of the reported drug-related adverse events were classified as gastrointestinal disorders that have been commonly reported with antibacterial drugs. These results indicate that CVA/AMPC (1:14) was clinically useful for the treatment of ABRS and is also suggested that was effective especially for the treatment of ABRS in children caused by beta-lactamase-producing bacteria including M. catarrhalis.

  19. Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study.

    Science.gov (United States)

    Ma, F; Yang, J; Kang, G; Sun, Q; Lu, P; Zhao, Y; Wang, Z; Luo, J; Wang, Z

    2016-09-01

    For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p <0.05) and that reported in participants administered HA-L (p <0.05). Additionally, 12 (25%) of the 48 randomized selected participants who received HA-L tested positive for HA antigen in stool samples. Hence, both HA-L and HA-I could provide acceptable immunogenicity in children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail.

  20. Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia De Lange syndrome.

    Science.gov (United States)

    Esposito, Susanna; Selicorni, Angelo; Daleno, Cristina; Valzano, Antonia; Cerutti, Marta; Galeone, Carlotta; Consolo, Silvia; Menni, Francesca; Principi, Nicola

    2011-06-01

    In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

  1. A New Recombinant BCG Vaccine Induces Specific Th17 and Th1 Effector Cells with Higher Protective Efficacy against Tuberculosis

    Science.gov (United States)

    da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

  2. Rotavirus vaccination and intussusception – Science, surveillance, and safety: A review of evidence and recommendations for future research priorities in low and middle income countries

    Science.gov (United States)

    Yen, Catherine; Healy, Kelly; Tate, Jacqueline E.; Parashar, Umesh D.; Bines, Julie; Neuzil, Kathleen; Santosham, Mathuram; Steele, A. Duncan

    2016-01-01

    ABSTRACT As of January 2016, 80 countries have introduced rotavirus vaccines into their national immunization programs. Many have documented significant declines in rotavirus-specific and all-cause diarrheal illnesses following vaccine introduction. Two globally licensed rotavirus vaccines have been associated with a low risk of intussusception in several studies. In July 2014, the Rotavirus Organization of Technical Allies Council convened a meeting of research and advocacy organizations, public health experts, funders, and vaccine manufacturers to discuss post-marketing intussusception surveillance and rotavirus vaccine impact data. Meeting objectives were to evaluate updated data, identify and prioritize research gaps, discuss best practices for intussusception monitoring in lower-income settings and risk communication, and provide insight to country-level stakeholders on best practices for intussusception monitoring and communication. Meeting participants agreed with statements from expert bodies that the benefits of vaccination with currently available rotavirus vaccines outweigh the low risk of vaccination-associated intussusception. However, further research is needed to better understand the relationship of intussusception to wild-type rotavirus and rotavirus vaccines and delineate potential etiologies and mechanisms of intussusception. Additionally, evidence from research and post-licensure evaluations should be presented with evidence of the benefits of vaccination to best inform policymakers deciding on vaccine introduction or vaccination program sustainability. PMID:27322835

  3. Meningococcal vaccine evolution

    Directory of Open Access Journals (Sweden)

    Gianni Bona

    2012-06-01

    Full Text Available Neisseria meningitidis is a leading cause of bacterial sepsis and meningitis worldwide. Although polysaccharide and glycoconjugate vaccines have been developed for serogroups A, C, Y and W-135, currently there are no broadly effective vaccines available for the prevention of meningococcal B disease. A general overview of the burden of the disease and the strains prevalence in the world with the focus in particular on the Italian situation is provided in this article, together with the vaccinations developed and under evaluation.

  4. Long-term immunogenicity assessment of a DTaP-IPV//PRP-T vaccine given at 2, 4, 6 and 18-19 months of age, and immunogenicity and safety of a DTaP-IPV vaccine given as a booster dose at 4 to 6 years of age in Thai children.

    Science.gov (United States)

    Pancharoen, Chitsanu; Chotpitayasunondh, Tawee; Chuenkitmongkol, Sunate; Ortiz, Esteban

    2012-05-01

    Booster vaccination of infants aims to further reduce the burden of childhood infectious diseases. This study assessed the antibody persistence induced by a primary series vaccination at 2, 4, 6 months of age and a first booster at 18-19 months of age with a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b combined vaccine (DTaP-IPV//PRP-T) in 4-6 year-old Thai children (N=123). The safety and immunogenicity of a tetravalent acellular pertussis combined vaccine (containing the same DTaP-IPV antigens as the previous vaccine) given as a second booster at 4 to 6 years of age was also evaluated. Seroprotective antibody levels against diphtheria (> or = 0.01 IU/ml), tetanus (> or = 0.10 IU/ml), and polioviruses (> or = 8 1/dil) were maintained 4-6 years after primary-vaccination and first booster by > or = 92.7% of children, and anti-pertussis antibodies > or = 5 EU/ml were observed in the majority of children. The second booster with DTaP-IPV elicited a strong response for all antigens. GMT or GMC ratios for all antigens at the pre- and post-booster samples were from 4.7 to 52.5. Primary vaccination at 2, 4, 6 and a booster at 18-19 months of age with the DTaP-IPV//PRP-T vaccine induced satisfactory antibody persistence at 4-6 years of age. A second booster with DTaP-IPV induced a strong immune response and was well tolerated.

  5. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

    Directory of Open Access Journals (Sweden)

    Laura Hewitson

    2014-01-01

    Full Text Available In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV. Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA, was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.

  6. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN® in 56-80-Year-Old Subjects.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA was assessed in a 56-80 years old population.MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120. Subjects received either two injections of MVA (MM group or one injection of Placebo and one injection of MVA (PM group four weeks apart. Safety was evaluated by assessment of adverse events (AE, focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA and a plaque reduction neutralization test (PRNT before and at different time points after vaccination.Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4 were as follows: Seroconversion (SC rates (doubling of titers from baseline in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%], and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]. Geometric mean titers (GMT measured by ELISA two weeks after the final vaccination for

  7. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects

    Science.gov (United States)

    Greenberg, Richard N.; Hay, Christine M.; Stapleton, Jack T.; Marbury, Thomas C.; Wagner, Eva; Kreitmeir, Eva; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P.; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2016-01-01

    Background Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56–80 years old population. Methods MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Results Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after

  8. Vacuna contra la fiebre hemorrágica argentina Candid#1 producida en la Argentina: Inmunogenicidad y seguridad Candid#1 vaccine against Argentine Hemorrhagic Fever produced in Argentina: Immunogenicity and safety

    Directory of Open Access Journals (Sweden)

    Delia A. Enria

    2010-06-01

    Full Text Available Se realizó un estudio clínico en 946 voluntarios humanos sanos, donde se comparó la vacuna Candid#1 producida en Argentina con la elaborada en EE.UU., que había sido utilizada en estudios previos. Como objetivo primario se evaluó la equivalencia en la eficacia utilizando como marcador subrogante a la inmunogenicidad medida por detección de anticuerpos neutralizantes. Como objetivo secundario se evaluó la equivalencia en inocuidad comparando las tasas de reacciones adversas. Ambas vacunas mostraron una tasa equivalente de inmunogenicidad ligeramente superior al 95.5%, que es la eficacia estimada para Candid #1 en estudios previos. No se observaron eventos adversos graves relacionados con la vacuna. Los eventos adversos generales considerados relacionados fueron de escasa significación clínica y de resolución espontánea o con tratamiento sintomático; se presentaron en los receptores de ambas vacunas en tasas equivalentes (29.9% para la vacuna fabricada en la Argentina y 35.0% para la fabricada en EE.UU., e incluyeron: cefalea, decaimiento, mialgias, plaquetopenia leve (A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slighty higher than the efficacy estimated from previous studies (95.5%. There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine were found for both vaccines. These included: headache, weakness, myalgias, mild low blood

  9. Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses

    DEFF Research Database (Denmark)

    Janitzek, Christoph M; Matondo, Sungwa; Thrane, Susan;

    2016-01-01

    system (SpyTag/SpyCatcher) and the immunogenicity is tested in mice. METHODS: Full-length 3d7 CSP protein was genetically fused at the C-terminus to SpyCatcher. The CSP-SpyCatcher antigen was then covalently attached (via the SpyTag/SpyCatcher interaction) to Acinetobacter phage AP205 VLPs which were...... modified to display one SpyTag per VLP subunit. To evaluate the VLP-display effect, the immunogenicity of the VLP vaccine was tested in mice and compared to a control vaccine containing AP205 VLPs plus unconjugated CSP. RESULTS: Full-length CSP was conjugated at high density (an average of 112 CSP...... molecules per VLP) to AP205 SpyTag-VLPs. Vaccination of mice with the CSP Spy-VLP vaccine resulted in significantly increased antibody titres over a course of 7 months as compared to the control group (2.6-fold higher at 7 months after immunization). Furthermore, the CSP Spy-VLP vaccine appears to stimulate...

  10. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142 administered intramuscularly with adjuvant system AS01

    Directory of Open Access Journals (Sweden)

    Otsyula Nekoye

    2013-01-01

    Full Text Available Abstract Background The development of an asexual blood stage vaccine against Plasmodium falciparum malaria based on the major merozoite surface protein-1 (MSP1 antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP142 has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites. Methods Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP142 in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP142 in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator. Results In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele previously tested at both study sites. Conclusions Given that the primary

  11. Safety, immunogenicity and duration of protection of the RTS,S/AS02(D malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial.

    Directory of Open Access Journals (Sweden)

    Pedro Aide

    Full Text Available BACKGROUND: The RTS,S/AS02(D vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants. METHODS AND FINDINGS: We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02(D given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001. We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02(D and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D, remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: -4.3-56.9, p = 0.076 over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003. CONCLUSION: The RTS,S/AS02(D malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT00197028.

  12. Bacterial dynamics in model cheese systems, aiming at safety and quality of Portuguese-style traditional ewe's cheeses.

    Science.gov (United States)

    Pereira, Cláudia I; Graça, João A; Ogando, Natacha S; Gomes, Ana M P; Malcata, F Xavier

    2009-11-01

    An experiment using model ewe's milk cheeses was designed to characterize microbial interactions that arise in actual raw milk cheese environments. These model cheeses were manufactured according to Portuguese artisanal practices, except that the microbial load and biodiversity were fully controlled: single potential pathogens and spoilage bacteria, or a combination thereof, were combined at various initial inoculum levels in sterilized raw ewe's milk with several lactic acid bacteria (LAB) normally found in traditional cheeses. Viable microbial counts were monitored throughout a 60-day ripening period. Two alternative mathematical approaches were used to fit the experimental data generated in terms of population dynamics: percent of inhibition and D-values. These were able to explain the complex competitive interactions between the contaminant microorganisms and the LAB adventitious populations. In general, the tested LAB were less able to inhibit contaminants present in combination and in higher concentrations. Lactococcus lactis, with its strong acidifying potential, was the most effective factor in controlling the unwanted bacterial population, especially single Staphylococcus aureus. The two lactobacilli studied, especially Lactobacillus brevis, were shown to be less effective; Escherichia coli and Listeria innocua were the contaminants least inhibited by the LAB.

  13. 9 CFR 113.67 - Erysipelothrix Rhusiopathiae Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Erysipelothrix Rhusiopathiae Vaccine... REQUIREMENTS Live Bacterial Vaccines § 113.67 Erysipelothrix Rhusiopathiae Vaccine. Erysipelothrix Rhusiopathiae Vaccine shall be prepared as a desiccated live culture of an avirulent or modified strain...

  14. Vaccine against human Papilloma Virus

    Directory of Open Access Journals (Sweden)

    Julio Cesar Reina

    2014-11-01

    Full Text Available At present two prophylactic human papilloma virus (HPV vaccines are commercially available. The Tetravalent vaccine against infection with four VPH types (6, 11, 16, and 18 distributed in the national program in Colombia and the Bivalent vaccine against the VPH types 16 and 18, respectively.  The efficacy and safety of both vaccines has periodically been assessed and they have been declared efficacious and safe by the health authorities of several countries and the Global Advisory Committee on Vaccine Safety ( GACVS of the World’s Health Organization (WHO.In its report of March 2014 the GACVS analyzed the evidence of the relationship between the  Human Papillomavirus Vaccine with  >175 million of doses distributed worldwide and autoimmune diseases, particularly Multiple Sclerosis, Aluminum as adjuvant, Vasculitis caused by vaccine DNA fragments and the Complex Regional Pain Syndrome described in Japan.   The Committee ratified the strict vaccine safety control and based on a thorough examination of existing evidence, reaffirmed that the risk-benefit profile remains favorable. The case of the children of Carmen de Bolivar in Colombia has been described by several authors in other countries as "Massive Psychogenic Event", which has absolute no relationship with the vaccine but its high media dissemination resulted into disastrous consequences for the national vaccination program

  15. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  16. The safety and efficacy of bacterial nanocellulose wound dressing incorporating sericin and polyhexamethylene biguanide: in vitro, in vivo and clinical studies.

    Science.gov (United States)

    Napavichayanun, Supamas; Yamdech, Rungnapha; Aramwit, Pornanong

    2016-03-01

    In our previous work, we have attempted to develop a novel bacterial nanocellulose wound dressing which composed of both polyhexamethylene biguanide (PHMB) as an antimicrobial agent and sericin as an accelerative wound healing component. The loading sequence and concentration of PHMB and sericin were optimized to provide the wound dressing with the most effective antimicrobial activity and enhanced collagen production. In this study, further in vitro, in vivo, and clinical studies of this novel wound dressing were performed to evaluate its safety, efficacy, and applicability. For the in vitro cytotoxic test with L929 mouse fibroblast cells, our novel dressing was not toxic to the cells and also promoted cell migration as good as the commercially available dressing, possibly due to the component of sericin released. When implanted subcutaneously in rats, the lower inflammation response was observed for the novel dressing implanted, comparing to the commercially available dressing. This might be that the antimicrobial PHMB component of the novel dressing played a role to reduce infection and inflammation reaction. The clinical trial patch test was performed on the normal skin of healthy volunteers to evaluate the irritation effect of the dressing. Our novel dressing did not irritate the skin of any volunteers, as characterized by the normal levels of erythema and melanin and the absence of edema, papule, vesicle, and bullae. Then, the novel dressing was applied for the treatment of full-thickness wounds in rats. The wounds treated with our novel dressing showed significantly lower percentage of wound size and higher extent of collagen formation mainly due to the activity of sericin. We concluded that our novel bacterial nanocellulose incorporating PHMB and sericin was a safe and efficient wound dressing material for further investigation in the wound healing efficacy in clinic.

  17. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    Science.gov (United States)

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination.

  18. Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study.

    Science.gov (United States)

    Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode

    2015-01-01

    Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children.

  19. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

    Science.gov (United States)

    Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

    2010-04-19

    This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.

  20. New recombinant vaccines for the prevention of meningococcal B disease

    Directory of Open Access Journals (Sweden)

    Taha MK

    2012-06-01

    Full Text Available Muhamed-Kheir Taha, Ala-Eddine DeghmaneInstitut Pasteur, Unit of Invasive Bacterial Infections and National Reference Center for Meningococci, Paris, FranceAbstract: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis that occurs as epidemic or sporadic cases. The causative agent, Neisseria meningitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no “universal” vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococcus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero®; Novartis, under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and therefore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the

  1. Technologies that make administration of vaccines safer.

    Science.gov (United States)

    Clements, C John; Larsen, Gordon; Jodar, Luis

    2004-05-01

    There is an ever-expanding technology that is aimed at making the administration of vaccines safer. Conventional ways of administering vaccines are being upgraded, modified or replaced by a wide variety of innovations. The paradigm of liquid vaccines, needles and syringes is slow to change, but already developments are occurring that will change for ever the way vaccines are administered and will improve the safety record of immunization. The oral route of vaccine administration has generally been thought of as safe, but until now only the polio vaccine has been widely used in this way. The conventional method of vaccine administration is by injection. Many ingenious devices have become available that now make injecting safer. Inventors are now looking imaginatively to alternative routes and technologies for delivering vaccines. Vaccines are generally manufactured to extremely high standards and rarely are shown to be the cause of safety issues. People remain the weakest safety link is vaccine administration. Technologies that bypasses the ability of man to make bad decisions or to behave incorrectly are of tremendous value. The vaccine world is in the middle of a radical re-think about how vaccines might best be administered. The presentation of the vaccine can be altered to fit new technologies such as powder jet guns, or skin patches. Even the conventional needle and syringe have evolved to much safer versions, and are set to continue this evolution. All this means even safer vaccines and their delivery.

  2. Nieuw vaccin tegen campylobacter

    NARCIS (Netherlands)

    Wagenaar, J.A.

    2008-01-01

    Het vaccin dat de kip moet beschermen tegen de bacterie Campylobacter werkt in het laboratorium. Dat wil bacterioloog Jaap Wagenaar wel kwijt. Wanneer het er komt en zelfs of het er komt, daarover laat Wagenaar zich niet uit. "Het is een hele klus om het immuunsysteem van kippen effectief op te late

  3. First evaluation of an influenza viral vector based Brucella abortus vaccine in sheep and goats: Assessment of safety, immunogenicity and protective efficacy against Brucella melitensis infection.

    Science.gov (United States)

    Tabynov, Kaissar; Yespembetov, Bolat; Matikhan, Nurali; Ryskeldinova, Sholpan; Zinina, Nadezhda; Kydyrbayev, Zhailaubay; Assanzhanova, Nurika; Tabynov, Kairat; Renukaradhya, Gourapura J; Mukhitdinova, Gulnara; Sansyzbay, Abylai

    2016-12-25

    Previously we developed and evaluated a candidate influenza viral vector based Brucella abortus vaccine (Flu-BA) administered with a potent adjuvant Montanide Gel01 in cattle, which was found safe and highly effective. This study was aimed to establish a proof-of-concept of the efficacy of Flu-BA vaccine formulation in sheep and goats. We vaccinated sheep and goats with Flu-BA vaccine and as a positive control vaccinated a group of animals with a commercial B. melitensis Rev.1 vaccine. Clinically, both Flu-BA and Rev.1 vaccines were found safe. Serological analysis showed the animals received Flu-BA vaccine did not induce antibody response against Brucella Omp16 and L7/L12 proteins during the period of our study (56days post-initial vaccination, PIV). But observed significant antigen-specific T cell response indicated by increased lymphocyte stimulation index and enhanced secretion of IFN-γ at day 56 PIV in Flu-BA group. The Flu-BA vaccinated animals completely protected 57.1% of sheep and 42.9% of goats against B. melitensis 16M challenge. The severity of brucellosis in terms of infection index and colonization of Brucella in tissues was significantly lower in the Flu-BA group compared to negative control animals group. Nevertheless, positive control commercial Rev.1 vaccine provided strong antigen-specific T cell immunity and protection against B. melitensis 16M infection. We conclude that the Flu-BA vaccine induces a significant antigen-specific T-cell response and provides complete protection in approximately 50% of sheep and goats against B. melitensis 16M infection. Further investigations are needed to improve the efficacy of Flu-BA and explore its practical application in small ruminants.

  4. Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine candidates against Johne's disease.

    Science.gov (United States)

    Settles, Erik W; Kink, John A; Talaat, Adel

    2014-04-11

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. Johne's disease has a severe economic impact on the dairy industry in the USA and worldwide. In an effort to combat this disease, we screened several transposon mutants that were attenuated in the murine model of paratuberculosis for the potential use as live attenuated vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with mutations of fabG2_2 and umaA1, respectively) were at or below the limit of detection for tissue colonization suggesting their low level persistence and hence safety. Prior to challenge, both candidates induced a M. paratuberculosis-specific IFN-γ, an indication of eliciting cell-mediated immunity. Following challenge with a virulent strain of M. paratuberculosis, the two vaccine candidates significantly reduced bacterial colonization in organs with reduced histological scores compared to control animals. In addition, one of the vaccine candidates (pgs3965) also induced IL-17a, a cytokine associated with protective immunity in mycobacterial infection. Our analysis suggested that the pgs3965 vaccine candidate is a potential live-attenuated vaccine that could be tested further in ruminant models of paratuberculosis. The analysis also validated our screening strategy to identify effective vaccine candidates against intracellular pathogens.

  5. Flu vaccination in pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Siettou

    2012-04-01

    Full Text Available In periods of seasonal influenza, during pandemic flu in the past and from recent experience that we have the emergence of influenza A (H1N1, pregnant compared with non-pregnant women are at increased risk to get sick and to develop serious complications up to mortality. Purpose: This paper examines the risks that arise for pregnant from contamination with the flu virus and the safety of influenza vaccination in pregnancy. Method: The method involves searching review and research studies in Pubmed data base mainly of the 2000 until 2009 and the words were used is pregnancy, flu vaccination, complications of the flu vaccination at the period of pregnancy. Results: Morbidity during periods of seasonal influenza in pregnant women is increased, while in times of pandemic are recorded fatalities. Based on this, specific recommendations have been made for a flu vaccination in pregnant women, both from the CDC, the American College of Obstetricians and Gynecologists in the U.S. and other official bodies like the World Health Organization, according to that the constitution of influenza vaccine in the pregnancy is necessary, given that the probability of morbidity in this period is increased at 10%. Conclusions: The studies so far to influenza vaccination in pregnancy, do not record serious complications for pregnant women and infants. However more research needs to be done on the safety of influenza vaccination in pregnancy.

  6. A retrospective survey of the safety of trivalent influenza vaccine among adults working in healthcare settings in south metropolitan Perth, Western Australia, in 2010.

    Science.gov (United States)

    McEvoy, Suzanne P

    2012-04-05

    In Australia, annual vaccination with trivalent influenza vaccine (TIV) is recommended for healthcare providers. Each year, an influenza vaccination program is run in south metropolitan area hospitals in Perth, Western Australia. In 2010, a survey to examine side effects following vaccination and subsequent significant respiratory illnesses during the influenza season was undertaken. A total of 2245 individuals vaccinated in the area-wide hospital vaccination program responded, representing 50% of consenting recipients. Data linkage was performed to ascertain additional information such as brand details. Side effects within 48 h of receipt of the influenza vaccine were reported by 387 (17.2%). Only 30 respondents (1.3%) had to seek health advice following a side effect temporally related to influenza vaccination and 10 (0.4%) required treatment. Recipients who received Fluvax®(364, 18.0%; CSL Biotherapies) were more likely to report side effects than those who received another brand (23, 10.2%; OR 1.94, 95% CI 1.24-3.03, P=0.004). The difference in the side effect profiles was largely confined to systemic effects. Most respondents (1621, 72.2%) did not require time off work for a respiratory illness during the subsequent influenza season. Overall, the influenza vaccine was demonstrated to be safe among this large sample of predominantly healthcare workers. A higher rate of adverse events, albeit primarily mild, was reported among recipients of Fluvax® in 2010.

  7. Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children.

    Science.gov (United States)

    Adderson, Elisabeth; Branum, Kristen; Sealy, Robert E; Jones, Bart G; Surman, Sherri L; Penkert, Rhiannon; Freiden, Pamela; Slobod, Karen S; Gaur, Aditya H; Hayden, Randall T; Allison, Kim; Howlett, Nanna; Utech, Jill; Allay, Jim; Knight, James; Sleep, Susan; Meagher, Michael M; Russell, Charles J; Portner, Allen; Hurwitz, Julia L

    2015-03-01

    Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-seropositive children in a dose escalation study. One dose of the vaccine (5 × 10(5), 5 × 10(6), or 5 × 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections.

  8. On the efficacy and safety of vaccination with live tachyzoites of Neospora caninum for prevention of neospora-associated fetal loss in cattle.

    Science.gov (United States)

    Weber, Fred H; Jackson, James A; Sobecki, Brian; Choromanski, Les; Olsen, Mary; Meinert, Todd; Frank, Rodney; Reichel, Michael P; Ellis, John T

    2013-01-01

    Infection of cattle with Neospora caninum may result in abortion or the birth of a congenitally infected calf. Vaccination with live N. caninum protects against experimental infection of cattle and mice, and the naturally attenuated Nc-Nowra strain of N. caninum is of particular interest as a potential vaccine candidate. Vaccination of heifers prior to breeding with live Nc-Nowra tachyzoites by either the subcutaneous or the intravenous route reduced the rate of abortion and the presence of the parasite in calves as determined by PCR and serology after infection of cows with a virulent isolate. Protected fractions were 55.6% to 85.2% depending on the route of vaccination and growth conditions of the vaccine strain, with cryopreserved Nc-Nowra tachyzoites being less effective, with a 25.9% protected fraction. Vaccination appeared to reduce the rate of pregnancy after artificial insemination in some groups compared to nonvaccinated, nonchallenged controls. One animal that was vaccinated but not challenged experienced an abortion, but Nc-Nowra could not be detected in any of the cows in this group or their progeny. This study confirms that live vaccination can be an effective method of preventing neosporosis in cattle and yet highlights the technical hurdle of preservation of live parasites that must be overcome for a vaccine to be commercially successful.

  9. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults

    DEFF Research Database (Denmark)

    Thierry-Carstensen, Birgit; Jordan, Karina; Uhlving, Hilde Hylland;

    2012-01-01

    Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults.......Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults....

  10. Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Thomas Stéphane

    2009-04-01

    Full Text Available Abstract Background When this trial was initiated, the combined measles, mumps and rubella (MMR vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro® and a varicella vaccine (VARIVAX® compared with the subcutaneous route. Methods An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374 or subcutaneously (SC group, n = 378. Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. Results Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml. Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm. There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes

  11. [Allergic alveolitis after influenza vaccination].

    Science.gov (United States)

    Heinrichs, D; Sennekamp, J; Kirsten, A; Kirsten, D

    2009-09-01

    Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.

  12. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  13. [Vaccination--General concepts. Systematic vaccination schedules for the child and adult in Spain. Impact of vaccination programs].

    Science.gov (United States)

    Arrazola Martínez, M Pilar; de Juanes Pardo, José Ramón; García de Codes Ilario, Aurelia

    2015-01-01

    One area of major importance in promoting health is the prevention of infectious diseases through vaccination. Vaccine is any preparation intended to generate immunity against a disease by stimulating the production of antibodies. There are two basic types: live attenuated and inactivated, with different characteristics that determine their use. The main properties of a vaccine are safety and protective efficacy. The vaccines can be administered based on individualized directions depending on various factors (personal, environmental…), or systematically as part of the immunization schedules. In Spain, the first childhood immunization schedule was implemented in 1975. The Autonomous Communities are currently responsible for establishing vaccine recommendations. The incidence of vaccine-preventable diseases and vaccination coverage are essential criteria for the evaluation of vaccination programs. In Spain the incidence of vaccine-preventable diseases is low. Vaccination coverage is high in childhood, but in adolescents, adults and groups at risk it is not always appropriate.

  14. Safety and Efficacy of an Intravaginal Prebiotic Gel in the Prevention of Recurrent Bacterial Vaginosis: A Randomized Double-Blind Study

    Directory of Open Access Journals (Sweden)

    Isabelle Coste

    2012-01-01

    Full Text Available Objective. This study was performed to evaluate the efficacy and safety of a prebiotic treatment in the balance recovery of the vaginal flora in subjects previously treated for bacterial vaginosis (BV. Study Design. A randomized trial was carried out on 42 subjects with an active prebiotic group compared to a placebo group. The main evaluation criterion was the quantification of the vaginal flora measured by the Nugent score. Secondary criteria included vaginal pH and BV recurrence. Results. After 8 days of treatment, all subjects who received the prebiotic had a normal Nugent score, whereas 33% of the subjects treated with placebo had an intermediate or positive Nugent score. After 16 days of application, a normal Nugent score was maintained in all subjects treated with the prebiotic, whereas in the placebo group 24% of the subjects still had an elevated Nugent score. Moreover, the maintenance of (or reversion to a normal flora was associated with the maintenance of (or reversion to physiological pH values. Conclusions. The intravaginal gel treatment improves the recovery of a normal vaginal flora after the treatment of a BV episode, which should warrant a reduction in the risk of further recurrences.

  15. Universal varicella vaccine immunization in Japan.

    Science.gov (United States)

    Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

    2016-04-07

    In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections.

  16. A randomized and controlled Phase 1 study of the safety and immunogenicity of the AMA1-C1/Alhydrogel + CPG 7909 vaccine for Plasmodium falciparum malaria in semi-immune Malian adults.

    Science.gov (United States)

    Sagara, Issaka; Ellis, Ruth D; Dicko, Alassane; Niambele, Mohamed B; Kamate, Beh; Guindo, Ousmane; Sissoko, Mahamadou S; Fay, Michael P; Guindo, Merepen A; Kante, Ousmane; Saye, Renion; Miura, Kazutoyo; Long, Carole; Mullen, Gregory E D; Pierce, Mark; Martin, Laura B; Rausch, Kelly; Dolo, Amagana; Diallo, Dapa A; Miller, Louis H; Doumbo, Ogobara K

    2009-12-09

    A double blind, randomized and controlled Phase 1 clinical trial was conducted to assess the safety and immunogenicity in malaria-exposed adults of the Plasmodium falciparum blood stage vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with and without the novel adjuvant CPG 7909. Participants were healthy adults 18-45 years old living in the village of Donéguébougou, Mali. A total of 24 participants received 2 doses one month apart of either 80 microg AMA1-C1/Alhydrogel or 80 microg AMA1-C1/Alhydrogel + 564 microg CPG 7909. The study started in October 2007 and completed follow up in May 2008. Both vaccines were well tolerated, with only mild local adverse events and no systemic adverse events judged related to vaccination. The difference in antibody responses were over 2-fold higher in the group receiving CPG 7909 for all time points after second vaccination and the differences are statistically significant (all pCPG 7909 in a malaria-exposed population.

  17. A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with sodium stibogluconate for the treatment of mucosal leishmaniasis.

    Science.gov (United States)

    Llanos-Cuentas, Alejandro; Calderón, Wessmark; Cruz, María; Ashman, Jill A; Alves, Fabiana P; Coler, Rhea N; Bogatzki, Lisa Y; Bertholet, Sylvie; Laughlin, Elsa M; Kahn, Stuart J; Beckmann, Anna Marie; Cowgill, Karen D; Reed, Steven G; Piazza, Franco M

    2010-10-28

    Adult patients with mucosal leishmaniasis (ML) were enrolled in a randomized, double-blind, placebo-controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 μg recombinant Leishmania polyprotein LEISH-F1 antigen+25 μg MPL(®)-SE adjuvant) (n=36) or saline placebo (n=12). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received standard chemotherapy with sodium stibogluconate starting on Day 0. The vaccine was safe and well tolerated, and induced both humoral and cell-mediated immune responses. Furthermore, intracellular cytokine staining showed an increase in the proportion of memory LEISH-F1-specific IL-2(+) CD4 T-cells after vaccination, which was associated with clinical cure. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in patients with ML.

  18. Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad(®)) in infants from 9 months of age.

    Science.gov (United States)

    Vesikari, Timo; Becker, Thomas; Gajdos, Vincent; Fiquet, Anne; Thomas, Stéphane; Richard, Patrick; Baudin, Martine

    2012-04-26

    Vaccination against measles, mumps, rubella and varicella (MMRV) is currently recommended in developed countries for infants from 12 months of age. However, measles vaccination at 9 months of age is recommended by the WHO in the Expanded Program on Immunization (EPI) schedule and it is therefore possible that MMR or MMRV vaccines might also be given at this age. This open-label, randomised, comparative study evaluated the immunogenicity and safety of a 2-dose schedule of ProQuad(®) (MMRV vaccine) given at a 3-month interval in healthy infants aged ≥9 months. For measles, the non-inferiority of the response rate post-Dose 2 was reached when Dose 1 was administered at 11 months (98%) compared with 12 months (99%) but was not reached when Dose 1 was administered at 9 months (95%). The response rate to measles post-Dose 1 increased with age, from 73% to 88% and 90% at 9, 11 and 12 months, respectively. For mumps, rubella and varicella, response rates were not different after Dose 1 (>95%) or Dose 2 (>99%) regardless of whether Dose 1 was administered at 9, 11 or 12 months of age. In conclusion, the age of administration of the first of a two-dose regimen of ProQuad may be lowered to 11 months. Dose 1 may be administered at 9 months if early protection is required, but it should be recognised that a second dose is required promptly with a minimum of 3-month interval between doses.

  19. Vaccination of cattle against bovine viral diarrhoea

    NARCIS (Netherlands)

    Oirschot, van J.T.; Bruschke, C.J.M.; Rijn, van P.A.

    1999-01-01

    This brief review describes types and quality (efficacy and safety) of bovine viral diarrhoea virus (BVDV) vaccines that are in the market or under development. Both conventional live and killed vaccines are available. The primary aim of vaccination is to prevent congenital infection, but the few va

  20. Vaccines for preventing Japanese encephalitis

    DEFF Research Database (Denmark)

    Schiøler, Karin Linda; Samuel, Miny; Wai, Kim Lay

    2007-01-01

    BACKGROUND: Vaccination is recognized as the only practical measure for preventing Japanese encephalitis. Production shortage, costs, and issues of licensure impair vaccination programmes in many affected countries. Concerns over vaccine effectiveness and safety also have a negative impact...... on acceptance and uptake. OBJECTIVES: To evaluate vaccines for preventing Japanese encephalitis in terms of effectiveness, adverse events, and immunogenicity. SEARCH STRATEGY: In March 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 1......), MEDLINE, EMBASE, LILACS, BIOSIS, and reference lists. We also attempted to contact corresponding authors and vaccine companies. SELECTION CRITERIA: Randomized controlled trials (RCTs), including cluster-RCTs, comparing Japanese encephalitis vaccines with placebo (inert agent or unrelated vaccine...

  1. [Results of Booster Vaccination in Children with Primary Vaccine Failure after Initial Varicella Vaccination].

    Science.gov (United States)

    Ozakiv, Takao; Nishimura, Naoko; Gotoh, Kensei; Funahashi, Keiji; Yoshii, Hironori; Okuno, Yoshinobu

    2016-05-01

    , antibody response than that after the initial vaccination (p vaccinations. A total of 185 participants responded to the questionnaire (response rate : 68%), and the period between receiving the initial vaccination and their response to the questionnaire ranged from 1.0 to 7.5 years (median : 4.0 years). The prevalence of breakthrough varicella after the initial vaccination was 17% among seroconverters who did not receive booster vaccination and 14% among non-seroconverters who received booster vaccination, showing no significant difference between the two groups. In conclusion, there are no safety issues regarding the administration of a booster vaccination to children with PVF after an initial varicella vaccination, and,a good antibody response can be expected.

  2. Current scenario of malaria vaccine

    Directory of Open Access Journals (Sweden)

    Jarnail Singh Braich

    2012-04-01

    Full Text Available Malaria is one of the deadliest infectious diseases that affects millions of people worldwide including India. As an addition to chemoprophylaxis and other antimalarial interventions malaria vaccine is under extensive research since decades. The vaccine development is more difficult to predict than drug development and presents a unique challenge as already there has been no vaccine effective against a parasite. Effective malaria vaccine could help eliminate and eradicate malaria; there are currently 63 vaccine candidates, 41 in preclinical and clinical stages of development. Vaccines are being designed to target pre-erythrocytic stages, erythrocytic stage or the sexual stages of Plasmodium taken up by a feeding mosquito, or the multiple stages. Two vaccines in preclinical and clinical development target P. falciparum; and the most advanced candidate is the pre-erythrocytic vaccine RTS,S which is in phase-III clinical trials. It is likely that world's first malaria vaccine will be available by 2015 at the country level. More efficacious second generation malaria vaccines are on the way to development. Safety, efficacy, cost and provision of the vaccine to all communities are major concerns in malaria vaccine issue. [Int J Basic Clin Pharmacol 2012; 1(2.000: 60-66

  3. Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses

    DEFF Research Database (Denmark)

    Janitzek, Christoph M; Matondo, Sungwa; Thrane, Susan;

    2016-01-01

    system (SpyTag/SpyCatcher) and the immunogenicity is tested in mice. METHODS: Full-length 3d7 CSP protein was genetically fused at the C-terminus to SpyCatcher. The CSP-SpyCatcher antigen was then covalently attached (via the SpyTag/SpyCatcher interaction) to Acinetobacter phage AP205 VLPs which were...... modified to display one SpyTag per VLP subunit. To evaluate the VLP-display effect, the immunogenicity of the VLP vaccine was tested in mice and compared to a control vaccine containing AP205 VLPs plus unconjugated CSP. RESULTS: Full-length CSP was conjugated at high density (an average of 112 CSP...

  4. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  5. Safety and efficacy of an E2 glycoprotein subunit vaccine produced in mammalian cells to prevent experimental infection with bovine viral diarrhoea virus in cattle.

    Science.gov (United States)

    Pecora, Andrea; Aguirreburualde, María Sol Pérez; Aguirreburualde, Alejandra; Leunda, Maria Rosa; Odeon, Anselmo; Chiavenna, Sebastián; Bochoeyer, Diego; Spitteler, Marcelo; Filippi, Jorge L; Dus Santos, Maria J; Levy, Susana M; Wigdorovitz, Andrés

    2012-09-01

    Bovine viral diarrhea (BVD) infection caused by bovine viral diarrhea virus (BVDV), a Pestivirus of the Flaviviridae family, is an important cause of morbidity, mortality and economical losses in cattle worldwide. E2 protein is the major glycoprotein of BVDV envelope and the main target for neutralising antibodies (NAbs). Different studies on protection against BVDV infection have focused on E2, supporting its putative use in subunit vaccines. A truncated version of type 1a BVDV E2 (tE2) expressed in mammalian cells was used to formulate an experimental oleous monovalent vaccine. Immunogenicity was studied through immunisation of guinea pigs and followed by trials in cattle. Calves of 8-12 months were vaccinated, twice with a 4 week interval, with either a tE2 subunit vaccine (n = 8), a whole virus inactivated vaccine (n = 8) or left untreated as negative control group (n = 8). Four weeks after the last immunisation the animals were experimentally challenged intranasally with a non-cythopathic BVDV strain. Following challenge, BVDV was isolated from all unvaccinated animals, while 6 out of 8 animals vaccinated with tE2 showed complete virological protection indicating that the tE2 vaccine presented a similar performance to a satisfactory whole virus inactivated vaccine.

  6. Human papillomavirus vaccination catch-up campaign in 2009 for girls born 1993 to 1996 in the Netherlands in 2009 : Results of the post-marketing safety suveillance

    NARCIS (Netherlands)

    van ' t Klooster TM; Kemmeren JM; Vermeer-de Bondt PE; Oostvogels B; PHaff TAJ; de Melker HE; van der Maas NAT; EPI; cib

    2011-01-01

    In 2009 zijn over de humaan papillomavirus (HPV) vaccinatie inhaalcampagne geen ernstige verschijnselen na vaccinatie gemeld die door het vaccin zijn veroorzaakt. Het vaccin kan daardoor op de korte termijn als veilig worden beoordeeld. Dit blijkt uit onderzoek naar de mogelijke bijwerkingen van het

  7. A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

    NARCIS (Netherlands)

    Tran, T.H.; Nguyen, T.D.; Nguyen, T.T.; Ninh, T.T.V.; Tran, N.B.C.; Nguyen, V.M.H.; Tran, T.T.N.; Cao, T.T.; Pham, V.M.; Nguyen, T.C.B.; Tran, T.D.H.; Pham, V.T.; To, S.D.; Campbell, J.I.; Stockwell, E.; Schultsz, C.; Simmons, C.P.; Glover, C.; Lam, W.; Marques, F.; May, J.P.; Upton, A.; Budhram, R.; Dougan, G.; Farrar, J.; Nguyen, V.V.C.; Dolecek, C.

    2010-01-01

    Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-) ssaV

  8. Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

    Science.gov (United States)

    Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna

    2016-04-01

    Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

  9. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  10. 76 FR 27059 - Solicitation of Written Comments on the Draft Report and Draft Recommendations of the Vaccine...

    Science.gov (United States)

    2011-05-10

    ... Vaccine Safety Working Group for Consideration by the National Vaccine Advisory Committee on the Federal Vaccine Safety System AGENCY: National Vaccine Program Office, Office of the Assistant Secretary for... National Vaccine Advisory Committee (NVAC) was established in 1987 to comply with Title XXI of the...

  11. Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.