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Sample records for vitespen vaccine clinical

  1. 42 CFR 70.9 - Vaccination clinics.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Vaccination clinics. 70.9 Section 70.9 Public... INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through contract or otherwise, authorized to administer vaccines and/or other prophylaxis. (b) A vaccination fee...

  2. Clinical malaria vaccine development.

    NARCIS (Netherlands)

    Sauerwein, R.W.

    2009-01-01

    Malaria is a major economic and public health problem in mainly sub-Saharan Africa. Globally 300-500 million new infections occur each year with 1-3 million fatal cases in particular young children. The most effective way to reduce disease and death from infectious diseases is to vaccinate

  3. HPV vaccine implementation in STD clinics--STD Surveillance Network.

    Science.gov (United States)

    Meites, Elissa; Llata, Eloisa; Hariri, Susan; Zenilman, Jonathan; Longfellow, Lisa; Schwebke, Jane; Tabidze, Irina; Mettenbrink, Christie; Jenkins, Heidi; Guerry, Sarah; Pathela, Preeti; Asbel, Lenore; Stover, Jeffrey A; Bernstein, Kyle; Kerani, Roxanne P; Dunne, Eileen F; Markowitz, Lauri E

    2012-01-01

    We surveyed selected public sexually transmitted disease clinics in the United States regarding human papillomavirus vaccine availability, target populations, funding sources, and barriers. Although nearly all had experience offering other vaccines, only 7 of 42 clinics (17%) offered human papillomavirus vaccine. Vaccine cost, staff time, and follow-up issues were commonly reported barriers.

  4. Clinical Trials of an Experimental Ebola Vaccine: A Canadian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This initiative supports phases 2 and 3 clinical trials of an experimental Ebola vaccine. The experimental vaccine is based on an attenuated recombinant Vesicular Stomatitis Virus vector (VSV-EBOV). The Public Health Agency of Canada developed the vaccine and licensed it to NewLink Genetics and Merck. Early vaccine ...

  5. Physician Attitudes Regarding School-Located Vaccination Clinics

    Science.gov (United States)

    Fiala, Steven C.; Cieslak, Paul R.; DeBess, Emilio E.; Young, Collette M.; Winthrop, Kevin L.; Stevenson, Ellen B.

    2013-01-01

    Background: School-located vaccination clinics offer an opportunity to target children for vaccination programs during communicable disease outbreaks. However, children in the United States are primarily vaccinated in the pediatrician's or family physician's office, and the concept of school-located vaccinations may be unfamiliar to some parents…

  6. Update on the Clinical Development of Candidate Malaria Vaccines

    National Research Council Canada - National Science Library

    Ballou, W. R; Arevalo-Herrera, Myriam; Carucci, Daniel; Richie, Thomas L; Corradin, Giampietro; Diggs, Carter; Druilhe, Pierre; Giersing, Birgitte K; Saul, Allan; Heppner, D. G

    2004-01-01

    ... powerful driver for stimulating clinical development of candidate vaccines for malaria. This new way forward promises to greatly increase the likelihood of bringing a safe and effective vaccine to licensure...

  7. 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

  8. Influenza Vaccinations, Fall 2009: Model School-Located Vaccination Clinics

    Science.gov (United States)

    Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

    2010-01-01

    The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…

  9. Promising practices for school-located vaccination clinics-- part II: clinic operations and program sustainability.

    Science.gov (United States)

    Lott, John; Johnson, Jennifer

    2012-03-01

    A school-located mass vaccination program can enable rapid vaccination of a large number of students while minimizing disruption of their school activities. During 3 consecutive influenza seasons beginning in 2005, the Knox County Health Department conducted school-located mass vaccination clinics using live attenuated influenza vaccine. Overall, the proportion of elementary schoolchildren vaccinated with live attenuated influenza vaccine exceeded 40% each year. We describe key lessons learned in clinic operations, including obtaining informed consent, defining the organizational structure and roles, preparing the school, staffing, training, supplies, vaccine management, team communication, and data management. We conclude by discussing program costs and sustainability.

  10. Malaria vaccine clinical trials: what’s on the horizon

    Science.gov (United States)

    Moreno, Alberto; Joyner, Chester

    2015-01-01

    Significant progress towards a malaria vaccine, specifically for Plasmodium falciparum, has been made in the past few years with the completion of numerous clinical trials. Each trial has utilized a unique combination of antigens, delivery platforms, and adjuvants, and the data that has been obtained provides critical information that has poises the research community for the development of next generation malaria vaccines. Despite the progress towards a P. falciparum vaccine, P. vivax vaccine research requires more momentum and additional investigations to identify novel vaccine candidates. In this review, recently completed and ongoing malaria vaccine clinical trials as well as vaccine candidates that are in the development pipeline are reviewed. Perspectives for future research using post-genomic mining, nonhuman primate models, and systems biology are also discussed. PMID:26172291

  11. Clinical guidance for smallpox vaccine use in a postevent vaccination program.

    Science.gov (United States)

    Petersen, Brett W; Damon, Inger K; Pertowski, Carol A; Meaney-Delman, Dana; Guarnizo, Julie T; Beigi, Richard H; Edwards, Kathryn M; Fisher, Margaret C; Frey, Sharon E; Lynfield, Ruth; Willoughby, Rodney E

    2015-02-20

    This report outlines recommendations for the clinical use of the three smallpox vaccines stored in the U.S. Strategic National Stockpile for persons who are exposed to smallpox virus or at high risk for smallpox infection during a postevent vaccination program following an intentional or accidental release of the virus. No absolute contraindications exist for smallpox vaccination in a postevent setting. However, several relative contraindications exist among persons with certain medical conditions. CDC recommendations for smallpox vaccine use were developed in consideration of the risk for smallpox infection, risk for an adverse event following vaccination, and benefit from vaccination. Smallpox vaccines are made from live vaccinia viruses that protect against smallpox disease. They do not contain variola virus, the causative agent of smallpox. The three smallpox vaccines stockpiled are ACAM2000, Aventis Pasteur Smallpox Vaccine (APSV), and Imvamune. Surveillance and containment activities including vaccination with replication-competent smallpox vaccine (i.e., vaccine viruses capable of replicating in mammalian cells such as ACAM2000 and APSV) will be the primary response strategy for achieving epidemic control. Persons exposed to smallpox virus are at high risk for developing and transmitting smallpox and should be vaccinated with a replication-competent smallpox vaccine unless severely immunodeficient. Because of a high likelihood of a poor immune response and an increased risk for adverse events, smallpox vaccination should be avoided in persons with severe immunodeficiency who are not expected to benefit from vaccine, including bone marrow transplant recipients within 4 months of transplantation, persons infected with HIV with CD4 cell counts smallpox virus exposure in persons with severe immunodeficiency. Persons without a known smallpox virus exposure might still be at high risk for developing smallpox infection depending on the magnitude of the outbreak and

  12. Cancer vaccines: from research to clinical practice

    National Research Council Canada - National Science Library

    Bot, Adrian; Obrocea, Mihail; Marincola, Francesco M

    2011-01-01

    ..., for both solid and blood borne cancers. Cancer Vaccines: Challenges and Opportunities in Translation is the first text in the field to bring immunotherapy treatments from the laboratory trial to the bedside for the practicing oncologist. Cancer Vaccines...

  13. Deconstructing the measure of vaccine efficacy against disease irrespective of HPV in HPV vaccine clinical trials.

    Science.gov (United States)

    Bautista, Oliver M; Luxembourg, Alain

    2016-03-01

    Human papillomavirus (HPV) vaccines were licensed by demonstrating prevention of anogenital disease caused by specific HPV types in clinical studies. Measuring the impact of HPV vaccination on the overall burden of anogenital disease (irrespective of HPV) is an important public health question which is ideally addressed in post-licensure epidemiological studies. Attempts were made to use clinical trial data for that purpose. However, the interpretation of vaccine efficacy on the endpoint of disease irrespective of HPV is not widely understood. We used the 9-valent HPV vaccine clinical program as a case study to determine the value of measuring vaccine efficacy in such endpoint. This assessment was rigorously performed by heuristic reasoning and through probability calculations. The measure of vaccine efficacy in the irrespective of HPV endpoint is driven simultaneously in opposite directions by the high estimate of prophylactic efficacy and a numerically negative estimate of risk reduction that is also a reflection of high prophylactic efficacy and no cross-protection. The vaccine efficacy estimate in the irrespective of HPV endpoint is ambiguous and difficult to interpret. Comparing this estimate across different HPV vaccine studies requires an understanding of the contributions of vaccine HPV type efficacy and the incidence of disease not related to vaccine HPV types for each study. Without such understanding, comparing studies and drawing conclusions from such comparison are highly misleading. Approaches are proposed to divide this endpoint in components that are easier to interpret. Copyright © 2016. Published by Elsevier Inc.

  14. Smallpox: clinical highlights and considerations for vaccination.

    Directory of Open Access Journals (Sweden)

    Mahoney M

    2003-01-01

    Full Text Available Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

  15. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren

    2003-01-01

    for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...... endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory...

  16. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    Science.gov (United States)

    2016-06-02

    vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. INTRODUCTION Filoviruses (the...Crucell Holland B.V. developed the Ad26-vectored EVD vaccine Ad26.ZEBOV based on extensive experience testing Ad26 and Ad35 vectors for malaria and...a vector in the development of vaccines against many diseases, including malaria , hepatitis C, influenza, and, of course, filovirus diseases

  17. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer. Copyright © 2015. Published by Elsevier B.V.

  18. Preclinical and clinical development of DNA vaccines for prostate cancer.

    Science.gov (United States)

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic. © 2013 Published by Elsevier Inc.

  19. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  20. Clinical trials with canine distemper vaccines in exotic carnivores.

    Science.gov (United States)

    Montali, R J; Bartz, C R; Teare, J A; Allen, J T; Appel, M J; Bush, M

    1983-12-01

    Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.

  1. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Boezen, H. Marike; Melief, Kees J. M.; Nijman, Hans W.

    Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical

  2. Parents who refuse or delay HPV vaccine: Differences in vaccination behavior, beliefs, and clinical communication preferences.

    Science.gov (United States)

    Gilkey, Melissa B; Calo, William A; Marciniak, Macary W; Brewer, Noel T

    2017-03-04

    We sought to estimate the national prevalence of HPV vaccine refusal and delay in a nationally-representative sample of parents of adolescents. We also compared parents who refused versus delayed HPV vaccine in terms of their vaccination beliefs and clinical communication preferences. In 2014 to 2015, we conducted an online survey of 1,484 US parents who reported on an 11- to 17-year-old child in their household. We used weighted multinomial logistic regression to assess correlates of HPV vaccine refusal and delay. Overall, 28% of parents reported that they had ever "refused or decided not to get" HPV vaccine for their child, and an additional 8% of parents reported that they had "delayed or put off getting" HPV vaccine. Compared to no refusal/delay, refusal was associated with lower confidence in adolescent vaccination (relative risk ratio [RRR] = 0.66, 95% confidence interval [CI], 0.48-0.91), lower perceived HPV vaccine effectiveness (RRR = 0.68, 95% CI, 0.50-0.91), and higher perceived harms (RRR = 3.49, 95% CI, 2.65-4.60). In contrast, delay was associated with needing more information (RRR = 1.76, 95% CI, 1.08-2.85). Most parents rated physicians and information sheets as helpful for making decisions about HPV vaccination, although parents who reported refusal endorsed these resources less often. Our findings suggest that HPV vaccine refusal is common among parents of adolescents and may have increased relative to previous estimates. Because the vaccination beliefs and communication preferences of parents who refuse appear to differ from those who delay, targeted communication strategies may be needed to effectively address HPV vaccine hesitancy.

  3. M2-based influenza vaccines: recent advances and clinical potential.

    Science.gov (United States)

    Kolpe, Annasaheb; Schepens, Bert; Fiers, Walter; Saelens, Xavier

    2017-02-01

    Current influenza vaccines can prevent disease caused by influenza viruses but require annual administration and almost yearly reformulation. An attractive alternative approach would be to use a vaccine that provides broad and, ideally, lifelong protection against all influenza A and B virus strains. The extracellular domain of matrix protein 2 (M2e) of influenza A viruses is conserved and thus fits well in such a broadly protective vaccine. Areas covered: Recent advances in M2e vaccine design, the mode of action of M2e-based immunity and clinical progress of M2-based influenza vaccines. Expert commentary: Many M2e vaccine have been successfully tested for efficacy against a panel of divergent influenza viruses in animal models. More recently, clinical studies have been conducted with M2e vaccine candidates, which demonstrated their safety and immunogenicity in humans. Efficacy studies in humans are still needed to provide evidence that an M2e-based vaccine can protect against human influenza.

  4. Integrating Clinical, Community, and Policy Perspectives on HPV Vaccination

    Science.gov (United States)

    Fernández, María E.; Allen, Jennifer D.; Mistry, Ritesh; Kahn, Jessica A.

    2010-01-01

    Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes associations between psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This paper summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated model can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research. PMID:20001821

  5. Seasonal Influenza Vaccine Uptake in a Respiratory Outpatients Clinic

    LENUS (Irish Health Repository)

    Rossiter, A

    2017-02-01

    Influenza is an acute viral respiratory illness that continues to cause significant morbidity and mortality in Ireland. Despite well-established national and international guidelines1 and increased public awareness campaigns, vaccine uptake rates are well below target worldwide2. We performed an audit of influenza vaccine uptake at a Respiratory outpatient clinic in a tertiary referral centre. 54% (n=41) of patients received the annual vaccine, well below the target of 75% set by the European Centre for Disease Prevention and Control (ECDC).

  6. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...... in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays...

  7. the infrastructure supporting hiv vaccine clinical trials

    African Journals Online (AJOL)

    vaccination is integrated into effective public health programmes. These include life skills education, sanitation, ... of protocol and amendments to the regulatory authorities and adherence to the requirements of these ... supported by an emergency care facility, pharmacy and laboratory, waiting and counselling areas, offices, ...

  8. Experimental human challenge infections can accelerate clinical malaria vaccine development

    NARCIS (Netherlands)

    Sauerwein, R.W.; Roestenberg, M.; Moorthy, V.S.

    2011-01-01

    Malaria is one of the most frequently occurring infectious diseases worldwide, with almost 1 million deaths and an estimated 243 million clinical cases annually. Several candidate malaria vaccines have reached Phase IIb clinical trials, but results have often been disappointing. As an alternative to

  9. Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia.

    Science.gov (United States)

    Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

    2015-01-01

    Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation.

  10. Bacille Calmette-Guerin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    NARCIS (Netherlands)

    Nissen, T.N.; Birk, N.M.; Smits, G.; Jeppesen, D.L.; Stensballe, L.G.; Netea, M.G.; Klis, F. van der; Benn, C.S.; Pryds, O.

    2017-01-01

    INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guerin (BCG)

  11. The comparative value of various employer-sponsored influenza vaccination clinics.

    Science.gov (United States)

    Zimmerman, Richard K; Wiringa, Ann E; Nowalk, Mary Patricia; Lin, Chyongchiou J; Rousculp, Matthew D; Mitgang, Elizabeth A; Lee, Bruce Y

    2012-09-01

    Many US firms offer influenza vaccination clinics to prevent lost productivity due to influenza. Strategies to promote and offer vaccination differ, and the economic value of the strategies is unknown. Decision analytic modeling and Monte Carlo probabilistic sensitivity analyses estimated the one-season cost-consequences of three types of influenza clinics (trivalent inactivated influenza vaccine only, vaccine choice [trivalent inactivated influenza or intranasal {live attenuated influenza} vaccine], or vaccine choice plus incentive) in firms of 50 and 250 employees, from the employer's perspective. On-site influenza vaccination was generally cost-saving over no vaccination. For the scenario of vaccine effectiveness of 70% and intermediate transmissibility, the incremental costs per employee for a firm of 50 employees were -$6.41 (ie, cost savings) for inactivated vaccine only versus no vaccination, -$1.48 for vaccine choice versus inactivated vaccine, and $1.84 for vaccine choice plus incentive versus vaccine choice. Clinics offering a choice of vaccines were slightly less costly under many scenarios. Generally, incremental costs were lower (1) in larger firms; (2) when influenza was assumed to be more contagious; and (3) when vaccine effectiveness was assumed to be higher. Employer-sponsored influenza vaccination clinics are generally cost-saving.

  12. Prostate cancer vaccines: the long road to clinical application.

    Science.gov (United States)

    Baxevanis, Constantin N; Papamichail, Michael; Perez, Sonia A

    2015-04-01

    Cancer vaccines as a modality of immune-based cancer treatment offer the promise of a non-toxic and efficacious therapeutic alternative for patients. Emerging data suggest that response to vaccination largely depends on the magnitude of the type I immune response generated, epitope spreading and immunogenic modulation of the tumor. Moreover, accumulating evidence suggests that cancer vaccines will likely induce better results in patients with low tumor burden and less aggressive disease. To induce long-lasting clinical responses, vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immune suppression. Immunotherapy, as a treatment modality for prostate cancer, has received significant attention in the past few years. The most intriguing characteristics that make prostate cancer a preferred target for immune-based treatments are (1) its relative indolence which allows sufficient time for the immune system to develop meaningful antitumor responses; (2) prostate tumor-associated antigens are mainly tissue-lineage antigens, and thus, antitumor responses will preferentially target prostate cancer cells. But, also in the event of eradication of normal prostate epithelium as a result of immune attack, this will have no clinical consequences because the prostate gland is not a vital organ; (3) the use of prostate-specific antigen for early detection of recurrent disease allows for the initiation of vaccine immunotherapy while tumor burden is still minimal. Finally, for improving clinical outcome further to increasing vaccine potency, it is imperative to recognize prognostic and predictive biomarkers of clinical benefit that may guide to select the therapeutic strategies for patients most likely to gain benefit.

  13. HPV vaccine cross-protection: Highlights on additional clinical benefit.

    Science.gov (United States)

    De Vincenzo, Rosa; Ricci, Caterina; Conte, Carmine; Scambia, Giovanni

    2013-09-01

    Prophylactic human papillomavirus (HPV) vaccines are administered in vaccination programs, targeted at young adolescent girls before sexual exposure, and in catch-up programs for young women in some countries. All the data indicate that HPV-virus-like particles (VLPs) effectively prevent papillomavirus infections with a high level of antibodies and safety. Since non-vaccine HPV types are responsible for about 30% of cervical cancers, cross-protection would potentially enhance primary cervical cancer prevention efforts. High levels of specific neutralizing antibodies can be generated after immunization with HPV VLPs. Immunity to HPV is type-specific. However, if we consider the phylogenetic tree including the different HPV types, we realize that a certain degree of cross-protection is possible, due to the high homology of some viral types with vaccine ones. The assessment of cross-protective properties of HPV vaccines is an extremely important matter, which has also increased public health implications and could add further value to their preventive potential. The impact of cross-protection is mostly represented by a reduction of cervical intraepithelial neoplasia CIN2-3 more than what expected. In this article we review the mechanisms and the effectiveness of Bivalent (HPV-16/-18) and Quadrivalent (HPV-6/-11/-16/-18) HPV vaccine cross-protection, focusing on the critical aspects and the potential biases in clinical trials, in order to understand how cross-protection could impact on clinical outcomes and on the new perspectives in post-vaccine era. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

    2017-01-01

    INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG......) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination...... or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. RESULTS: Among the 300 included...

  15. Pre-clinical and clinical development of the first placental malaria vaccine.

    Science.gov (United States)

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G; Nielsen, Morten A

    2017-06-01

    Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical vaccine development. However, all papers from these searches were not systematically included. Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine.

  16. A short clinical review of vaccination against measles.

    Science.gov (United States)

    Tannous, Leen Khader; Barlow, Gavin; Metcalfe, Neil H

    2014-04-01

    Major epidemics of measles are again in the news across the UK because of our failure to maintain population herd immunity. This situation has occurred primarily because of a loss of public confidence in the measles, mumps and rubella (MMR) vaccine, which was never restored following the Wakefield debacle, and a lack of awareness of the potential morbidity and mortality associated with measles. This article provides healthcare professionals with a succinct overview of important clinical aspects of measles and also describes the history of measles vaccination in the UK. Restoration of herd immunity will require higher public acceptance of the MMR vaccine in the context of recognition that measles remains an important infection. While achievement of this appears to be challenging, recent UK-based research suggests that it can be ascertained.

  17. TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

    Directory of Open Access Journals (Sweden)

    Stefan H. E. Kaufmann

    2017-10-01

    Full Text Available TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC. It aims at the discovery and development of novel tuberculosis (TB vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.

  18. Clinical vaccine development for H5N1 influenza.

    Science.gov (United States)

    Clegg, Christopher H; Rininger, Joseph A; Baldwin, Susan L

    2013-07-01

    H5N1 is a highly pathogenic avian influenza virus that can cause severe disease and death in humans. H5N1 is spreading rapidly in bird populations and there is great concern that this virus will begin to transmit between people and cause a global crisis. Vaccines are the cornerstone strategy for combating avian influenza but there are complex challenges for pandemic preparedness including the unpredictability of the vaccine target and the manufacturing requirement for rapid deployment. The less-than-optimal response against the 2009 H1N1 pandemic unmasked the limitations associated with influenza vaccine production and in 2010, the President's Council of Advisors on Science and Technology re-emphasized the need for new recombinant-based vaccines and adjuvants that can shorten production cycles, maximize immunogenicity and satisfy global demand. In this article, the authors review the efforts spent in developing an effective vaccine for H5N1 influenza and summarize clinical studies that highlight the progress made to date.

  19. Effect of booster doses of poliovirus vaccine in previously vaccinated children, Clinical Trial Results 2013.

    Science.gov (United States)

    Habib, Muhammad Atif; Soofi, Sajid; Mach, Ondrej; Samejo, Tariq; Alam, Didar; Bhatti, Zaid; Weldon, William C; Oberste, Steven M; Sutter, Roland; Bhutta, Zulfiqar A

    2016-07-19

    Considering the current polio situation Pakistan needs vaccine combinations to reach maximum population level immunity. The trial assessed whether inactivated poliovirus vaccine (IPV) can be used to rapidly boost immunity among children in Pakistan. A five-arm randomized clinical trial was conducted among children (6-24months, 5-6years and 10-11years). Children were randomized in four intervention arms as per the vaccines they received (bOPV, IPV, bOPV+vitamin A, and bOPV+IPV) and a control arm which did not receive any vaccine. Baseline seroprevalence of poliovirus antibodies and serological immune response 28days after intervention were assessed. The baseline seroprevalence was high for all serotypes and the three age groups [PV1: 97%, 100%, 96%, PV2: 86%, 100%, 99%, PV3: 83%, 95%, 87% for the three age groups respectively]. There was significantly higher rate of immune response observed in the study arms which included IPV (95-99%) compared with bOPV only arms (11-43%), [p0.5]. IPV has shown the ability to efficiently close existing immunity gaps in a vulnerable population of children in rural Pakistan. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The status of vaccine availability and associated factors in Tshwane government clinics.

    Science.gov (United States)

    Ngcobo, Ntombenhle Judith; Kamupira, Mercy G

    2017-05-24

    Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA) is no exception, as there are indications of vaccine stock-outs in clinics. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA). A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should be restructured and overhauled with the use of advances in technology

  1. The status of vaccine availability and associated factors in Tshwane government clinics

    Directory of Open Access Journals (Sweden)

    Ntombenhle Judith Ngcobo

    2017-06-01

    Full Text Available Background. Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA is no exception, as there are indications of vaccine stock-outs in clinics. Objective. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. Methods. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA. Results. A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Conclusion. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should

  2. Transmission blocking malaria vaccines: Assays and candidates in clinical development.

    Science.gov (United States)

    Sauerwein, R W; Bousema, T

    2015-12-22

    Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

  3. [Research progress regarding the clinical evaluation on recombinant human papillomavirus vaccines].

    Science.gov (United States)

    He, W G; Zhao, J; Huang, S J; Wu, T

    2016-06-01

    Human papillomavirus (HPV) is the main cause for cervical cancer, anogenital cancers and genital warts. Three HPV vaccines have been licensed abroad. Data from clinical trials showed high efficacy of the HPV vaccines in young women with 90%-100% vaccine-related HPV diseases prevented. Though efficacy of the vaccine appears lower in older women, this population can still benefit from vaccination. Immunobriging trials show that the two-dose schedule in 9-14 years old girls elicits non-inferior immune response than the three-dose one in young adults. In addition, HPV vaccines can reduce the recurrent rates in CIN2+ patients after therapeutic surgery and the vaccines have cross-protection aganist diseases caused by non-vaccine type HPV. Safety data on HPV vaccines are assuring. Thus HPV vaccine should be widely used in adolescent girls and women of appropriate age groups.

  4. Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine.

    Science.gov (United States)

    Spiri, Andrea M; Rodriguez-Campos, Sabrina; Matos, José M; Glaus, Tony M; Riond, Barbara; Reusch, Claudia E; Hofmann-Lehmann, Regina; Willi, Barbara

    2017-05-25

    Leptospirosis is a re-emerging bacterial zoonosis caused by spirochetes of the genus Leptospira. Severe disease has been reported in dogs in Europe despite vaccination with bivalent Leptospira vaccines. Recently, a tetravalent canine Leptospira vaccine (Nobivac® L4) was licenced in Europe. The goal of this study was to investigate clinical signs, microscopic agglutination test (MAT) titres, haematology, blood biochemistry, cardiac (c) Troponin I levels and echocardiography before and after vaccination with this tetravalent vaccine. Forty-eight healthy dogs were prospectively enrolled and vaccinated twice, 3-4 weeks apart (T0 and T1). Before vaccination (T0) and 16-31 days after the second vaccination (T2), MAT (n = 48), haematology (n = 48), blood biochemistry (n = 36) and cTroponin I measurements (n = 29) were performed, and MAT was repeated 347-413 days after the second vaccination (T3, n = 44). Echocardiography was performed before the first and second vaccination (T0 and T1, n = 24). Mild and transient clinical signs within 5 days following the first and second vaccination occurred in 23% and 10% of the dogs, respectively. Before the first vaccination (T0), all dogs showed negative MAT titres for the tested serovars except for Canicola (50% with titres 100-400). At T2, positive MAT titres to the serovars Canicola (100%), Australis (89%), Grippotyphosa (86%), Bratislava (60%), Autumnalis (58%), Copenhageni (42%), Pomona (12%), Pyrogenes (8%) and Icterohaemorrhagiae (2%) were found. Median to high titres (≥ 400) were most common to the serovar Canicola (92%) and less common to the serovars Australis (41%), Grippotyphosa (21%), Bratislava (12%), Autumnalis (4%), Pyrogenes (4%) and Pomona (2%). At T3, positive MAT titres (titre range: 100-400) were found in 2-18% of the dogs to serovars of the vaccine serogroups and in 2-18% of the dogs to the non-vaccine serovars Pomona, Autumnalis, Pyrogenes and Ballum. Haematology, blood biochemistry, c

  5. [Preventive vaccines and immunotherapy clinical trials against cervical cancer].

    Science.gov (United States)

    Valdespino-Gómez, Víctor Manuel

    2005-01-01

    Cervical cancer (CC) is a public health problem among women worldwide, especially in emerging nations. To improve CC control, new adjuvant therapeutic strategies are required. Advances in immunology, genomics and proteomics have accelerated our understanding of the genetic and cellular basis of many cancer types. CC is a member of virus-related neoplasms and its initiation and promotion is associated with persistent infection of oncogenic human papillomavirus. During viral infection and associated-transforming developing lesions, the HPVs co-express non-structural and structural proteins. These early or late proteins are the antigenic target of the immune response. The intervention to stimulate the humoral or cellular immune anti-HPV response is the objective of the immunoprevention and immunotherapy against CC. Recently in a controlled phase III trial of HPV type 16 vaccine using virus-like particles of L1 capsid of HPV-16, the incidence was reduced of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Although preliminary results of immunotherapy clinical trials against CC did not modify the clinical status, they occasionally show improvement of lymphocyte response against HPV. A recent immunotherapy trial using dendritic cells pulsed with HPV-18 E7 oncoprotein as adjuvant resulted in temporal remission and improved performance status in a patient with metastatic CC. New and different vaccine preventive trials against HPV are being put into practice and clinically tested. It is hoped that in the future it may be possible to eradicate cervical cancer. The success of immunotherapy anti-HPV clinical trials in CC patients will be determined at a future time. The scientific basis for the development of papillomavirus prophylactic and therapeutic vaccines against persistent infection and preinvasive-invasive associated cervical lesions along with the present status of immunopreventive and immunotherapy clinical trials against cervical cancer

  6. Lyme borreliosis: reviewing potential vaccines, clinical aspects and health economics.

    Science.gov (United States)

    Šmit, Renata; Postma, Maarten J

    2015-01-01

    Lyme borreliosis (LB) is a multisystem infectious disease with a growing burden in many parts of North America, Asia and Europe. Persistent infection of LB can usually be treated effectively with antibiotic therapy, but it may be followed by post-treatment Lyme disease syndrome. Therefore, it is important to begin with treatment in the early phase of the disease. Vaccination shows potential as the most effective way of preventing LB and reducing its burden in these continents. It is concluded that there is a need for continuous effort in research from all perspectives on LB, especially regarding prevention with novel vaccines, their development, clinical efficacy and cost-effectiveness. This review may help to further develop (cost-) effective strategies for prevention and control of the disease to reduce its burden and achieve population-wide health benefits.

  7. [PAPILLOMAVIRUS INFECTION: PRINCIPLE CHARACTERISTICS, CLINICAL MANIFESTATIONS, VACCINE PROPHYLAXIS].

    Science.gov (United States)

    Lopukhov, P D; Briko, N I; Khaldin, A A; Tsapkova, N N; Lupashko, O V

    2016-01-01

    Papillomaviruses are a large and diverse group of viruses. It includes approximately 200 fully described types that have been detected in humans. Human papilloma viruses (HPV) are etiologic agents during various, benign and malignant lesions of mucous membrane and skin epithelium. Very importantly, persistent HPV infection of certain types is a leading cause of carcinoma of uterine cervix, penis, vulva; vagina, anal canal and fauces (including tongue base and tonsils). HPV infection prophylaxis is the best means to control HPV-conditioned diseases, and vaccination, as had been demonstrated, --the most effective method of its prophylaxis. In this paper principle characteristics and clinical manifestations of papillomavirus infection, as well as effectiveness of vaccination against HPV are examined.

  8. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    Science.gov (United States)

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  9. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2010-02-01

    Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

  10. Vaccination and Clinical Severity: Is the Effectiveness of Contact Tracing and Case Isolation Hampered by Past Vaccination?

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    Hiroshi Nishiura

    2013-02-01

    Full Text Available While contact tracing and case isolation are considered as the first choice of interventions against a smallpox bioterrorist event, their effectiveness under vaccination is questioned, because not only susceptibility of host and infectiousness of case but also the risk of severe clinical manifestations among cases is known to be reduced by vaccine-induced immunity, thereby potentially delaying the diagnosis and increasing mobility among vaccinated cases. We employed a multi-type stochastic epidemic model, aiming to assess the feasibility of contact tracing and case isolation in a partially vaccinated population and identify data gaps. We computed four epidemiological outcome measures, i.e., (i the threshold of a major epidemic under the interventions; (ii the expected total number of cases; (iii the probability of extinction, and (iv the expected duration of an outbreak, demonstrating that all of these outcomes critically depend on the clinical impact of past vaccination on the diagnosis and movement of vaccinated cases. We discuss that, even in the absence of smallpox in the present day, one should consider the way to empirically quantify the delay in case detection and an increase in the frequency of contacts among previously vaccinated cases compared to unvaccinated during the early stage of an epidemic so that the feasibility of contact tracing and case isolation in a vaccinated population can be explicitly assessed.

  11. Vaccines licensed and in clinical trials for the prevention of dengue.

    Science.gov (United States)

    Torresi, J; Ebert, G; Pellegrini, M

    2017-05-04

    Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

  12. Improving influenza vaccination in chronically ill children using a tertiary-care based vaccination clinic: Is there a role for the live-attenuated influenza vaccine (LAIV)?

    Science.gov (United States)

    Merckx, Joanna; McCormack, Deirdre; Quach, Caroline

    2016-02-03

    Children with underlying medical conditions should receive influenza vaccine (IV) yearly; yet this remains sub-optimal. We aimed to describe our experience with a tertiary-care hospital-based influenza vaccination clinic for this at-risk population. From October to December 2012, 2013, and 2014, we ran an influenza vaccination clinic at the Montreal Children's Hospital, where children with high-risk conditions come for their follow-up. Both injectable IV (IIV) and live-attenuated IV (LAIV) were offered free of charge to patients and their household contacts. Upon vaccination, parents were asked to fill a pre-piloted questionnaire. We vaccinated a total of 2640 high-risk children and 1912 household members during the three influenza vaccination seasons. In 2012 and 2013, 631 and 630 patients with chronic illnesses were vaccinated, compared to 1379 in 2014. Caregivers preferred LAIV primarily because no needle was involved (49.0%) and because it was perceived as less painful (46.9%). LAIV was administered to 69% (2012), 55% (2013) and 47% (2014) of high-risk children. The main reason for not receiving LAIV was because it was contra-indicated. A small fraction of children previously vaccinated with LAIV who did not present any contraindication to LAIV opted for IIV: 12/101 (11.8%) in 2013 and 16/272 (5.9%) in 2014. In 2014, this was mainly due to a previous negative experience with LAIV (11/16). Having an influenza vaccination clinic on site at a tertiary care hospital, where children come for their scheduled visits, facilitates yearly influenza vaccination in children with chronic illnesses. LAIV is preferred by caregivers and patients, when not contraindicated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.

    Science.gov (United States)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby; Jeppesen, Dorthe Lisbeth; Stensballe, Lone Graff; Netea, Mihai G; van der Klis, Fiona; Benn, Christine Stabell; Pryds, Ole

    2017-04-11

    BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Xenogeneic cell-based vaccine therapy for colorectal cancer: Safety, association of clinical effects with vaccine-induced immune responses.

    Science.gov (United States)

    Seledtsova, G V; Shishkov, A A; Kaschenko, E A; Seledtsov, V I

    2016-10-01

    An accumulating body of evidence suggests that xenogeneic vaccines can be very effective in breaking the immune tolerance to human tumor-associated antigens (TAAs). We assessed adverse effects, as well as clinical and immune responses induced by a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells in 60 stage IV colorectal cancer patients. Neither grade III/IV toxicities, nor laboratory and clinical signs of systemic severe autoimmune disorders were documented in any XPV-treated patient. Clinical effects of various grades (complete response, partial response and disease stabilization) with duration of no shorter than 6 months was observed in 25 (41.67%) vaccinated patients. The average survival time of the XPV-treated patients was markedly longer than that of the clinically matched control patients (20 vs. 7 months). The overall 3-year survival rate in the XPV-treated and control group was 16.7% (10 patients) and 0%, respectively. Following a course of ten XPV vaccinations, peripheral blood mononuclear cell (PBMC) proliferation assays revealed increased T-cell immune responses to human Caco-2 colon adenocarcinoma-associated antigens. In addition, relative contents of CD25+ FoxP3+regulatory T-cells in patients with proven immunotherapy-mediated clinical effects (responders) were significantly decreased in the blood, which was paralleled by marked increases in serum levels of proinflammatory cytokines, such as interferon-alpha (IFN-α), IFN-ɣ, and interleukin-8 (IL-8). Serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-4, and IL-6 were not affected in both responder and non-responder patients. In conclusion, this study provides evidence for the safety, clinical feasibility and immunogenicity of xenogeneic composite cell vaccine administration in colorectal cancer patients. This is the first demonstration that clinical effects of such a vaccine are associated with vaccine-induced, proinflammatory

  15. Transposon leads to contamination of clinical pDNA vaccine.

    Science.gov (United States)

    van der Heijden, I; Gomez-Eerland, R; van den Berg, J H; Oosterhuis, K; Schumacher, T N; Haanen, J B A G; Beijnen, J H; Nuijen, B

    2013-07-11

    We report an unexpected contamination during clinical manufacture of a Human Papilomavirus (HPV) 16 E6 encoding plasmid DNA (pDNA) vaccine, with a transposon originating from the Escherichia coli DH5 host cell genome. During processing, presence of this transposable element, insertion sequence 2 (IS2) in the plasmid vector was not noticed until quality control of the bulk pDNA vaccine when results of restriction digestion, sequencing, and CGE analysis were clearly indicative for the presence of a contaminant. Due to the very low level of contamination, only an insert-specific PCR method was capable of tracing back the presence of the transposon in the source pDNA and master cell bank (MCB). Based on the presence of an uncontrolled contamination with unknown clinical relevance, the product was rejected for clinical use. In order to prevent costly rejection of clinical material, both in-process controls and quality control methods must be sensitive enough to detect such a contamination as early as possible, i.e. preferably during plasmid DNA source generation, MCB production and ultimately during upstream processing. However, as we have shown that contamination early in the process development pipeline (source pDNA, MCB) can be present below limits of detection of generally applied analytical methods, the introduction of "engineered" or transposon-free host cells seems the only 100% effective solution to avoid contamination with movable elements and should be considered when searching for a suitable host cell-vector combination. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Clinical safety and efficacy of first indigenous recombinant hepatitis B vaccine.

    Science.gov (United States)

    Kumar, A; Joshi, N; Sreenivas, D V; Palan, S; Nagarjuna Kumar, Y R

    1998-07-01

    A pilot study was conducted to assess the clinical safety and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac B) in 18 healthy adults. 20 microg of vaccine was administered at 0, 1 and 2 months. Protective anti HBs titres developed in 22%, 77% and 100% one month after 1st, 2nd and 3rd dose of vaccination, respectively. The geometric mean titre after the 3rd dose was 1015.29 mIu/ml. The vaccine was well tolerated with minor local and systemic side effects in 28% and 22%, respectively. The indigenously developed recombinant hepatitis B vaccine is safe, well tolerated and highly immunogenic.

  17. Adjuvants for Leishmania vaccines: From Models to Clinical Application

    Directory of Open Access Journals (Sweden)

    Vanitha S. Raman

    2012-06-01

    Full Text Available Two million new cases of leishmaniasis occur every year, with the cutaneous leishmaniasis (CL presentation accounting for approximately two-thirds of all cases. Despite the high incidence rates and geographic expansion of the disease, CL remains a neglected tropical disease without effective intervention strategies. Efforts to address this deficit have given rise to the experimental murine model of CL. By virtue of its simplicity and pliability, the CL model has been used to provide substantial information regarding cellular immunity, as well as in the discovery and evaluation of various vaccine adjuvants. The CL model has facilitated in vivo studies of the mechanism of action of many adjuvants, including the TLR4 agonist MPL, the TLR7/8 agonist Imiquimod, the TLR9 agonist CpG, adenoviral vectors and the immunostimulatory complexes (ISCOM. Together, these studies have helped to unveil the requirement for certain types of immune responses at specific stages of CL disease and provide a basis to aid the design of effective second-generation vaccines for human CL. This review focuses on adjuvants that have been tested in experimental CL, outlining how they have helped advance our understanding of the disease and ultimately, how they have performed when applied within clinical trials against human CL.

  18. Clinical Trials of an Experimental Ebola Vaccine: A Canadian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Early vaccine trials During the multicentre phase 1 trials, researchers demonstrated the vaccine's safety and its ability to provoke an immune response (immunogenicity). The next trials will determine the expanded safety, protective immune response, and efficacy of the vaccine with at-risk populations in Africa. The trials will ...

  19. School-Located Vaccination Clinics: Then and Now

    Science.gov (United States)

    Mazyck, Donna

    2010-01-01

    School-located vaccination has a long history in the United States. The 2008 Advisory Committee on Immunization Practices (ACIP) recommendation for annual influenza vaccination of all children 6 months through 18 years of age adds approximately 30 million individuals to the overall cohort recommended to have a yearly vaccination. The ability to…

  20. SELF WOUND MANAGEMENT PRACTICES BEFORE ATTENDING ANTIRABIES VACCINE CLINIC

    Directory of Open Access Journals (Sweden)

    Amit Kumar Mishra, Smita Panda, Prakash Chandra Panda

    2015-07-01

    Full Text Available Introduction: In INDIA almost 20000 people die (40% of world death each year from rabies. Most of these deaths could be prevented by post exposure prophylaxis with wound washing, rabies immunoglobulin & vaccination. Local wound management alone can reduce viral load by up to 80%. Objective: To study self-wound management practices in animal exposure patients before attending a tertiary level ARV clinic. Methodology: Data regarding wound management was collected by individual interview of patients attending the ARV clinic during OCT 2011 to MAR 2012. The data collected in the form of a questionnaire. Analysis of data was done in the Department Of Community Medicine, V.S.S. Medical College, Burla. Results: Total 493 cases of animal exposure were attended during the study period. Most common biting animal was dog (94.5%. 31% of cases were under the age of 10 years & 23% belongs to the age of 10-19 years. Male to female ratio was 3:1. Most of the cases (91% were of category III exposure. Immediate management of wound was practiced by 63-77% of cases before visiting ARV clinic; only 2% wash the wound with running water & soap for 15 minutes. 39% of cases applied Dettol/savlon at the wound side & other 38% applied turmeric, red chilli, kerosene, Band-Aid & ghee locally. Most cases (61% reported to ARV clinic within 24hours.

  1. Clinical Trials Using Adenovirus Encoding Tyrosinase/MART-1/MAGEA6-transduced Autologous Dendritic Cell Vaccine

    Science.gov (United States)

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus encoding tyrosinase/mart-1/magea6-transduced autologous dendritic cell vaccine.

  2. Immunopathogenesis associated with formaldehyde-inactivated RSV vaccine in preclinical and clinical studies.

    Science.gov (United States)

    Muralidharan, Abenaya; Li, Changgui; Wang, Lisheng; Li, Xuguang

    2017-04-01

    Respiratory syncytial virus (RSV) infection is responsible for one-third of deaths of acute lower respiratory infection in children less than one-year-old. The formaldehyde-inactivated RSV vaccine trial conducted in the 1960s predisposed the vaccinees to more serious RSV infection instead of protection. Better understanding of the underlying mechanism is of critical importance for better designing of safe and effective RSV vaccines. Areas covered: PubMed was searched to review immunopathology induced by RSV vaccines. We intend to dissect the differences in clinical and pathological manifestations of enhanced respiratory disease (ERD) in different animal models in comparison with humans. Formaldehyde-inactivated RSV vaccine causes ERD in both humans and animals, while RSV vaccine without formaldehyde treatment could also induce similar disease in animals, suggesting multiple pathways may be involved. Expert commentary: Identification of biomarkers pertinent to clinical evaluation should be further explored for safety assessment of RSV vaccines in human trials.

  3. An experimental vaccine for calf pneumonia caused by Mycoplasma bovis: clinical, cultural, serological and pathological findings.

    Science.gov (United States)

    Nicholas, Robin A J; Ayling, Roger D; Stipkovits, Laszlo P

    2002-10-04

    A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3-4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.

  4. Low vaccination rates among patients with rheumatoid arthritis in a German outpatient clinic.

    Science.gov (United States)

    Krasselt, Marco; Ivanov, Jean-Philipp; Baerwald, Christoph; Seifert, Olga

    2017-02-01

    Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections due to two reasons: the disease itself and the immunosuppressive therapy. Vaccinations against preventable diseases are therefore of utmost importance for these group of patients. To estimate vaccination frequencies among patients with rheumatoid arthritis, we studied patients in a survey and calculated vaccination rates based on their vaccination documents. Patients have been recruited from our outpatient clinic during one of their routine visits. For the statistical analysis, they have been divided by age (≥60 vs vaccination rates, in particular for the strongly recommended vaccines against Pneumococcus and Influenza (33 and 53%, respectively). Furthermore, protection rates for important basic vaccinations, e.g. against Pertussis, were found to be very low with 12% only. Beside these findings, we saw age-dependent differences for a variety of vaccines: while Pneumococcus and Influenza vaccines were more often given to patients ≥60 years, MMR, Pertussis, Diphtheria and Hepatitis were significantly more often applied to younger patients. Vaccination rates have to be improved among RA patients, in particular for vaccines protecting from respiratory tract infections such as Pneumococcus.

  5. Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases.

    Science.gov (United States)

    Dasari, Vijayendra; Smith, Corey; Khanna, Rajiv

    2013-06-01

    It is now well over a decade since the US Institute of Medicine of the National Academy of Sciences assigned the highest priority for a vaccine to prevent congenital human CMV infection, which was subsequently endorsed by the US National Vaccine Program Office. In spite of extensive efforts over many years, successful licensure of a CMV vaccine formulation remains elusive. While the understanding of immune regulation of CMV infection in healthy virus carriers and diseased patients has dramatically improved, traditional vaccine development programs have failed to exploit this knowledge. Until recently, most efforts have concentrated on designing vaccine formulations that block CMV infection through neutralizing antibodies. However, studies carried out in various disease settings, especially in transplant patients, have clearly emphasized the importance of cellular immunity and it is indeed encouraging to see that recent CMV vaccine development programs have started to incorporate this arm of the immune system. A number of new vaccine candidates have been found to be effective in preclinical studies, and are able to induce CMV-specific immune responses in clinical studies, although firm evidence for long-term efficacy is not yet available. For successful implementation of these vaccines in clinical settings, it will be important to demonstrate that the vaccine can induce effective levels of immunity for prevention of transmission of viral infection from mother to unborn baby and thus reduce CMV-related pathogenesis. For transplant recipients, vaccine strategies should be aimed at the induction of immunity that restricts viral reactivation and limits development of disease.

  6. Pre-clinical toxicology considerations for vaccine development.

    Science.gov (United States)

    Al-Humadi, Nabil

    2017-10-13

    Vaccine development requires pre-clinical toxicology studies, following good laboratory practice (GLP), before first in human (phase I) use. Many factors are critical in the final outcome of any pre-clinical toxicology study. The study design is one of these critical factors and should be carefully planned to avoid any false negative and/or false positive results. Preparation is another most critical factor in a successful study. Major changes in any procedure during the course of study should be avoided by all means. For example, if the protocol specified the tail as the site of blood collection and this procedure was used for the control group at the day of necropsy, this collection site should never be replaced by another site (e.g. foot, eye, or heart) in all other treatment groups. Food restrictions and acute restraint stress affect clinical pathology data and should be avoided in rodents. Institutional Animal Care and Use Committee (IACUC) guidelines for frequent blood collections (weekly, monthly, or at necropsy) in any animal species should be strictly followed. Clinical pathology data will be profoundly affected by any diversion from the recommended volumes. If CO2 is specified in the protocol for anesthesia and/or euthanasia, ensuring enough quantity to use for all groups at necropsy is a very important factor. Using two different anesthetics in any study (e.g. CO2 vs. pentobarbital) may result in false positive or false negative results in clinical chemistry parameters. Quality assurance elements (SOPs, instrument validation, lab certification etc.) affect the data interpretation and the final outcome of any toxicology study. SOPs should be up to date and written clearly. All lab instruments should be validated and all laboratories should be certified. Published by Elsevier Ltd.

  7. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hansen, Troels Holz; Andersen, Mads Hald

    2009-01-01

    which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which...... are frequently claimed to have a possible influence on clinical response. These parameters include performance status, type of antigen, DC maturation status, route of vaccine administration, use of adjuvant, and vaccine induced immune response. In total, 38 articles found through Medline search, have been...... = 0.09), and use of autologous antigen preparation (p = 0.12). The categorisation of SD in the response group is debatable. Nevertheless, when the SD group were analysed separately we found that SD was significantly associated with use of peptide antigens (p = 0.0004), use of adjuvant (p = 0...

  8. Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

    Science.gov (United States)

    Fletcher, Mark A.; Fritzell, Bernard

    2012-01-01

    Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

  9. The development and clinical evaluation of second-generation leishmaniasis vaccines.

    Science.gov (United States)

    Duthie, Malcolm S; Raman, Vanitha S; Piazza, Franco M; Reed, Steven G

    2012-01-05

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1+MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Key Components of a School-Located Vaccination Clinic: Lessons Learned from Fall 2009

    Science.gov (United States)

    Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

    2010-01-01

    The 2009 H1N1 influenza A virus vaccination campaign focused on use of school-located vaccination (SLV) clinics because of the ability of SLV to reach targeted populations. Large numbers of children are found in schools, and schools are conveniently located throughout communities. Communities are generally familiar with and trust schools, and…

  11. HPV vaccination intention among male clients of a large STI outpatient clinic in Amsterdam, the Netherlands

    NARCIS (Netherlands)

    Marra, E.; Alberts, C.J.; Zimet, G.D.; Paulussen, T.G.W.M.; Heijman, T.; Hogewoning, A.A.; Sonder, G.J.B.; Fennema, J.S.; Vries, H.J.C. de; Schim van der Loeff, M.F.

    2016-01-01

    We explored HPV vaccination intention and its determinants among male clients of the sexually transmitted infections (STI) clinic in Amsterdam. In 2015, male clients aged ≥18 years were invited to complete a web-based questionnaire regarding HPV vaccination intention and socio-psychological

  12. Clinical effectiveness of first and repeat influenza vaccination in adult and elderly diabetic patients

    NARCIS (Netherlands)

    Looijmans-Van den Akker, I.; Verheij, T.J.M.; Buskens, E.; Nichol, K.L.; Rutten, G.E.H.M.; Hak, E.

    OBJECTIVE: Influenza vaccine uptake remains low among the high-risk group of patients with diabetes, partly because of conflicting evidence regarding its potential benefits. We assessed the clinical effectiveness of influenza vaccination in adults with diabetes and specifically examined potential

  13. Frederick National Lab Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR

    Science.gov (United States)

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  14. Leidos Biomed Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR Staging

    Science.gov (United States)

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  15. Vaccinations Administered During Off-Clinic Hours at a National Community Pharmacy: Implications for Increasing Patient Access and Convenience

    Science.gov (United States)

    Goad, Jeffery A.; Taitel, Michael S.; Fensterheim, Leonard E.; Cannon, Adam E.

    2013-01-01

    PURPOSE Approximately 50,000 adults die annually from vaccine-preventable diseases in the United States. Most traditional vaccine providers (eg, physician offices) administer vaccinations during standard clinic hours, but community pharmacies offer expanded hours that allow patients to be vaccinated at convenient times. We analyzed the types of vaccines administered and patient populations vaccinated during off-clinic hours in a national community pharmacy, and their implications for vaccination access and convenience. METHODS We retrospectively reviewed data for all vaccinations given at the Walgreens pharmacy chain between August 2011 and July 2012. The time of vaccination was categorized as occurring during traditional hours (9:00 am–6:00 pm weekdays) or off-clinic hours, consisting of weekday evenings, weekends, and federal holidays. We compared demographic characteristics and types of vaccine. We used a logistic regression model to identify predictors of being vaccinated during off-clinic hours. RESULTS During the study period, pharmacists administered 6,250,402 vaccinations, of which 30.5% were provided during off-clinic hours: 17.4% were provided on weekends, 10.2% on evenings, and 2.9% on holidays. Patients had significantly higher odds of off-clinic vaccination if they were younger than 65 years of age, were male, resided in an urban area, and did not have any chronic conditions. CONCLUSIONS A large proportion of adults being vaccinated receive their vaccines during evening, weekend, and holiday hours at the pharmacy, when traditional vaccine providers are likely unavailable. Younger, working-aged, healthy adults, in particular, a variety of immunizations during off-clinic hours. With the low rates of adult and adolescent vaccination in the United States, community pharmacies are creating new opportunities for vaccination that expand access and convenience. PMID:24019274

  16. Development of Human Papillomavirus (HPV) Vaccines: A Review of Literature and Clinical Update.

    Science.gov (United States)

    Sangar, Vikrant Chadrakant; Ghongane, Balasaheb; Mathur, Gaurav

    2016-01-01

    The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil®; - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

  17. School-Located Influenza Vaccination Clinics: Local Health Department Perspectives

    Science.gov (United States)

    Ransom, James

    2009-01-01

    Universal childhood influenza vaccination presents challenges and opportunities for health care and public health systems to vaccinate the children who fall under the new recommendation. Advisory Committee on Immunization Practices (ACIP) recommendations and guidelines are helpful, but they do not provide strategies on how to deliver immunization…

  18. Clinical effectiveness of conventional influenza vaccination in asthmatic children

    NARCIS (Netherlands)

    Smits, A J; Hak, E; Stalman, W A B; van Essen, G A; Hoes, A W; Verheij, Th J M

    Influenza immunization rates among young asthmatics remain unsatisfactory due to persistent concern about the impact of influenza and the benefits of the vaccine. We assessed the effectiveness of the conventional inactivated trivalent sub-unit influenza vaccine in reducing acute respiratory disease

  19. Assessing vaccine efficacy for the prevention of acute otitis media by pneumococcal vaccination in children: a methodological overview of statistical practice in randomized controlled clinical trials.

    Science.gov (United States)

    Jahn-Eimermacher, Antje; du Prel, Jean-Baptist; Schmitt, Heinz-Josef

    2007-08-14

    Acute otitis media (AOM) is the most common bacterial infectious disease among children. Vaccination is proposed to prevent otitis and several clinical trials were performed to assess the efficacy of pneumococcal vaccines. The way vaccine efficacy is analysed varies among trials. However, the clinical meaning of an estimate of vaccine effect and its statistical test depends on the applied statistical method. We aim to bring the meaning and validity of statistical trial results to the attention of researchers. We consider all methodological approaches for analysing vaccine efficacy applied in pneumococcal vaccination trials included in a recent Cochrane Review. We demonstrate how different methods address different scientific questions on the effect of vaccination, how they can complement each other and why some methods can produce misleading results.

  20. Multilevel correlates for human papillomavirus vaccination of adolescent girls attending safety net clinics.

    Science.gov (United States)

    Tiro, Jasmin A; Pruitt, Sandi L; Bruce, Corinne M; Persaud, Donna; Lau, May; Vernon, Sally W; Morrow, Jay; Skinner, Celette Sugg

    2012-03-16

    Adolescent HPV vaccination in minority and low income populations with high cervical cancer incidence and mortality could reduce disparities. Safety-net primary care clinics are a key delivery site for improving vaccination rates in these populations. To examine prevalence of HPV initiation (≥ 1 dose), completion (receipt of dose 3 within 12 months of initiation), and receipt of 3 doses in four safety-net clinics as well as individual-, household-, and clinic-level correlates of initiation. We used multilevel modeling to investigate HPV initiation among 700 adolescent females who sought primary care in four safety-net clinics in Dallas, Texas from March 2007 to December 2009. Data were abstracted from patients' paper and electronic medical records. HPV vaccine uptake varied significantly by clinic. Across clinics, initiation was 36.6% and completion was 39.7% among those who initiated. In the total study population, only 15.7% received all three doses. In multivariate, two-level logistic regression analyses, initiation was associated with receipt of other adolescent vaccines, influenza vaccination in the year prior to data abstraction, being sexually active, and having more chart documentation (presence of health maintenance questionnaire and/or immunization record). There was no association between initiation and age, race/ethnicity, or insurance status. In four urban safety-net clinics, HPV initiation rates paralleled 2008 national rates. The correlation of HPV initiation with other adolescent vaccines underscores the importance of reviewing vaccination status at every health care visit. HPV vaccine uptake in safety-net clinics should continue to be monitored to understand impact on cervical cancer disparities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. A review of malaria vaccine clinical projects based on the WHO rainbow table

    Science.gov (United States)

    2012-01-01

    Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below. PMID:22230255

  2. A review of malaria vaccine clinical projects based on the WHO rainbow table

    Directory of Open Access Journals (Sweden)

    Schwartz Lauren

    2012-01-01

    Full Text Available Abstract Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below.

  3. A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Stanley A. Plotkin

    2012-01-01

    Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

  4. Future paths for HIV vaccine research: Exploiting results from recent clinical trials and current scientific advances.

    Science.gov (United States)

    Bansal, Geetha P; Malaspina, Angela; Flores, Jorge

    2010-02-01

    More than 60 million individuals have been infected with HIV and approximately half of these individuals have died since the epidemic started. The quest for an effective vaccine to prevent HIV transmission, which is likely to be the most effective approach to halt the epidemic, has been and continues to be an insurmountable challenge. Traditional vaccine strategies that have been effective for other vaccines have proven unsuccessful or impractical for HIV because of safety concerns. Nonetheless, substantial efforts have been directed at the development and clinical testing of HIV vaccines during the past two decades. Four major HIV vaccine efficacy trials conducted by VaxGen Inc (AIDSVAX 003 and AIDSVAX 004) and the NIH-supported HIV Vaccine Trials Network (HVTN 502 and HVTN 503) failed to demonstrate efficacy; however, a recent trial conducted in Thailand (RV144 trial) demonstrated a low level of efficacy, resulting in some renewed optimism. Dissecting the causes for vaccine failure and, more importantly, for the partial level of efficacy observed in the RV144 trial should provide important guidance to the field. This review discusses the ongoing HIV vaccine trials and also highlights recent scientific advances that have provided the field with new leads to invigorate the search for effective vaccines.

  5. Prevention of clinical coliform mastitis in dairy cows by a mutant Escherichia coli vaccine.

    Science.gov (United States)

    González, R N; Cullor, J S; Jasper, D E; Farver, T B; Bushnell, R B; Oliver, M N

    1989-01-01

    A prospective cohort study was undertaken in two commercial California dairies. The treatment group, 246 cows, received three doses of a whole cell bacterin of J5 Escherichia coli (mutant of E. coli O111:B4) plus Freund's incomplete adjuvant vaccine (two in the dry period and one after calving) while 240 unvaccinated cows served as controls. Thirty-five cases of clinical coliform mastitis were diagnosed, six in vaccinated cows and 29 in unvaccinated cows. Bacteria isolated from the clinical cases included 15 E. coli five Klebsiella pneumoniae, three K. oxytoca, three K. ozaenae, five Enterobacter aerogenes, three Serratia marcescens and one Serratia spp. Four control cows were culled, three of them because of chronic coliform mastitis and one because of postcoliform infection agalactia. Incidence rate of clinical gram-negative mastitis was 2.57% in vaccinated cows and 12.77% in unvaccinated cows. The estimated risk ratio, the measure of risk of having clinical gram-negative mastitis for vaccinated cows to unvaccinated cows, was 0.20 (p less than 0.005), indicating a strong relationship between vaccination and lack of clinical gram-negative mastitis. The results of this trial indicate that the administration of the E. coli J5 vaccine is protective against natural challenge to gram-negative bacteria, and reduces the incidence of clinical gram-negative mastitis in dairy cows during the first three months of lactation. PMID:2670166

  6. Hepatitis B vaccine antibody response and the risk of clinical AIDS or death.

    Directory of Open Access Journals (Sweden)

    Michael L Landrum

    Full Text Available Whether seroresponse to a vaccine such as hepatitis B virus (HBV vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death.From a large HIV cohort, we evaluated those who received HBV vaccine only after HIV diagnosis and had anti-HBs determination 1-12 months after the last vaccine dose. Non-response and positive response were defined as anti-HBs <10 and ≥ 10 IU/L, respectively. Participants were followed from date of last vaccination to clinical AIDS, death, or last visit. Univariate and multivariable risk of progression to clinical AIDS or death were evaluated with Cox regression models. A total of 795 participants vaccinated from 1986-2010 were included, of which 41% were responders. During 3,872 person-years of observation, 122 AIDS or death events occurred (53% after 1995. Twenty-two percent of non-responders experienced clinical AIDS or death compared with 5% of responders (p<0.001. Non-response to HBV vaccine was associated with a greater than 2-fold increased risk of clinical AIDS or death (HR 2.47; 95% CI, 1.38-4.43 compared with a positive response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed type hypersensitivity skin test responses (an in vivo marker of cell-mediated immunity. This association remained evident among those with CD4 count ≥ 500 cells/mm³ (HR 3.40; 95% CI, 1.39-8.32.HBV vaccine responses may have utility in assessing functional immune status and risk stratificating HIV-infected individuals, including those with CD4 count ≥ 500 cells/mm³.

  7. 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.

  8. Clinical development of a Vero cell culture-derived seasonal influenza vaccine.

    Science.gov (United States)

    Ehrlich, Hartmut J; Berezuk, Gregory; Fritsch, Sandor; Aichinger, Gerald; Singer, Julia; Portsmouth, Daniel; Hart, Mary Kate; El-Amin, Wael; Kistner, Otfried; Barrett, P Noel

    2012-06-19

    technology has the potential to make a substantial contribution to improving influenza vaccine supply. The studies are registered with ClinicalTrials.gov, numbers NCT00566345 and NCT00782431. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era

    DEFF Research Database (Denmark)

    Pedersen, T.I.; Howitz, M.; Andersen, Christian Østergaard

    2010-01-01

    P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were 24 years old [median 62 years (range 25....... The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H...

  10. Demographic and clinical factors associated with response to smallpox vaccine in preimmunized volunteers.

    Science.gov (United States)

    Bossi, Philippe; Gay, Frédérick; Fouzai, Imène; Combadière, Béhazine; Brousse, Geneviève; Lebrun-Vignes, Bénédicte; Crance, Jean-Marc; Autran, Brigitte; Garin, Daniel

    2008-01-01

    In March 2003, the French Ministry of Health implemented a program on preparedness and response to a biological attack using smallpox as weapon. This program included the establishment of a preoutbreak national team that could be revaccinated against smallpox. To identify demographic and clinical factors associated with vaccination success defined as the presence of a pustule at the inoculation site at day 8 (days 7-9), with an undiluted vaccinia virus derived from a Lister strain among preimmunized volunteers. From March 2003 to November 2006, we have studied prospectively 226 eligible volunteers. Demographic data were recorded for each volunteer (age, sex, number of previously smallpox vaccinations and date of the last vaccination). Smallpox vaccine adverse reactions were diagnosed on the basis of clinical examination performed at days 0, 7, 14, 21 and 28 after revaccination. A total of 226 volunteers (sex ratio H/F = 2.7) were revaccinated. Median age was 45 years (range: 27-63 yrs). All volunteers completed follow-up. Median number of vaccinations before revaccination was 2 (range: 1-8). The median delay between time of the study and the last vaccination was 29 years (range; 18-60 yrs). Sixty-one volunteers (27%) experienced one (n = 40) or more (n = 21) minor side effects during the 2-14 days after revaccination. Successful vaccination was noted in 216/226 volunteers (95.6%) at day 8 and the median of the pustule diameter was 5 mm (range: 1-20 mm). Size of the pustule at day 8 was correlated with age (p = 0.03) and with the presence of axillary adenopathy after revaccination (p = 0.007). Sex, number of prior vaccinations, delay between the last vaccination and revaccination, and local or systemic side effects with the exception of axillary adenopathy, were not correlated with the size of the pustule at day 8. Previously vaccinated volunteers can be successfully revaccinated with the Lister strain.

  11. Vaccination strategies against highly pathogenic arenaviruses: the next steps toward clinical trials.

    Directory of Open Access Journals (Sweden)

    Stephan Olschläger

    Full Text Available Vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. However, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. This is particularly problematic as these diseases are notoriously difficult to diagnose and treat. Lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, particularly in Nigeria. Annually, an estimated 300,000 humans are infected and several thousands succumb to the disease. The successful development of the vaccine "Candid#1" against Junin virus, the causative agent of Argentine hemorrhagic fever, proved that an effective arenavirus vaccine can be developed. Although several promising studies toward the development of a Lassa fever vaccine have been published, no vaccine candidate has been tested in human volunteers or patients. This review summarizes the immunology and other aspects of existing experimental arenavirus vaccine studies, discusses the reasons for the lack of a vaccine, and proposes a plan for overcoming the final hurdles toward clinical trials.

  12. Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

    Science.gov (United States)

    Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

    2016-10-26

    With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Promising practices for school-located vaccination clinics--part I: preparation.

    Science.gov (United States)

    Lott, John; Johnson, Jennifer

    2012-03-01

    A school-located mass vaccination clinic approach can enable rapid vaccination of a large number of students while minimizing disruption of their school activities and potentially reducing missed work hours by parents. During 3 consecutive influenza seasons beginning in 2005, the Knox County Health Department conducted school-located mass vaccination clinics using live attenuated influenza vaccine. Clinics were held each year throughout the county over 4 weeks in more than 100 public and private schools for more than 65, 000 students in Grades K to 12. Overall, the proportion of all students vaccinated at school each year exceeded 40%. Our experience indicated that careful and thorough planning was essential to program success. Critical planning elements included (1) initial planning with extensive lead time to find the proper lead agency and project leader and to develop sound comprehensive vaccine clinic planning; (2) developing partnerships, especially with schools; (3) communicating successfully with parents, children, school administrators and teachers, medical providers, and the community at large; and (4) educating these groups successfully, using good timing, through local media, school events, direct mailings (including parents receiving information and consent packets), and partners. We review here the details of these key planning elements.

  14. Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya.

    Directory of Open Access Journals (Sweden)

    Borna A Nyaoke

    Full Text Available 1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as 'advancing research' and collaboration with science, and personal benefits such as health benefits and financial interests.A thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site.Of the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research.The majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine

  15. Vaccinations

    Science.gov (United States)

    ... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...

  16. Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research

    Directory of Open Access Journals (Sweden)

    Elena Mata

    2013-01-01

    Full Text Available There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants as well as the immunostimulatory effect of the formulation components (immunostimulants modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.

  17. Malaria vaccine adjuvants: latest update and challenges in preclinical and clinical research.

    Science.gov (United States)

    Mata, Elena; Salvador, Aiala; Igartua, Manoli; Hernández, Rosa María; Pedraz, José Luis

    2013-01-01

    There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.

  18. Conceptual framework for behavioral and social science in HIV vaccine clinical research

    Science.gov (United States)

    Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.

    2011-01-01

    HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083

  19. Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

    Directory of Open Access Journals (Sweden)

    R. Vermeij

    2011-01-01

    Full Text Available Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients.

  20. Conceptual framework for behavioral and social science in HIV vaccine clinical research.

    Science.gov (United States)

    Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P

    2011-10-13

    HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd.

  1. Patient and clinic factors associated with adolescent human papillomavirus vaccine utilization within a university-based health system.

    Science.gov (United States)

    Dempsey, Amanda; Cohn, Lisa; Dalton, Vanessa; Ruffin, Mack

    2010-01-22

    We reviewed clinical and billing data from a university-based health system to assess HPV vaccine utilization among 9-18-year-old girls by individual, visit and medical specialty characteristics. Our sample included 10,082 adolescent patients with 27,928 visits to outpatient family medicine (FM), pediatric and gynecology clinics between January 2007 and March 2008. Vaccine series completion was low among eligible adolescents (15%), with important disparities in vaccine utilization by medical specialty, age, race and insurance status. Missed opportunities for vaccination were common. Our findings may help to target future interventions aimed at increasing adolescent HPV vaccine utilization.

  2. Prospects for subunit vaccines: Technology advances resulting in efficacious antigens requires matching advances in early clinical trial investment.

    Science.gov (United States)

    McClean, Siobhán

    2016-12-01

    With the continued march of antimicrobial resistance, a renewed impetus for better vaccines has been heralded. Identification of potent subunit vaccines has been greatly facilitated by recent developments in reverse vaccinology and proteomics strategies. There are a range of antimicrobial resistant bacterial pathogens that could be targeted by potent vaccine antigens identified within the coming years. However, cost is a significant hurdle in progressing lead antigen candidates to clinical trials. In order for novel vaccine technologies to realize their clinical potential, there is a requirement to improve investment and incentives to expedite the development of vaccines that are apparently efficacious in preclinical trials.

  3. Effect of modified live or inactivated feline herpesvirus-1 parenteral vaccines on clinical and laboratory findings following viral challenge.

    Science.gov (United States)

    Summers, Stacie C; Ruch-Gallie, Rebecca; Hawley, Jennifer R; Lappin, Michael R

    2017-08-01

    Objectives The objective was to investigate the effect of one dose of an inactivated feline herpesvirus-1 (FHV-1), feline calicivirus (FCV) and panleukopenia virus (FPV) vaccine (FVRCP) or one dose of a modified live (ML) FVRCP vaccine on clinical signs and shedding of FHV-1 in specific pathogen-free kittens after challenge with FHV-1 7 days after vaccination. Methods Twenty-four FHV-1 seronegative 5-month-old kittens were randomized into three groups of eight kittens. Group 1 kittens were maintained as unvaccinated controls, group 2 kittens were administered one dose of the inactivated FVRCP vaccine subcutaneously (SC) and group 3 kittens were administered one dose of the ML FVRCP vaccine SC. All 24 cats were administered FHV-1 by nasal and oropharyngeal inoculation 7 days later and were observed daily for clinical signs of illness for 21 days. Results In the 21 days after FHV-1 challenge, both groups of vaccinated cats were less likely to be clinically ill (indicated by lower cumulative clinical scores) than control cats ( P vaccinated groups ( P = 0.97). Although the total clinical score was similar between both vaccines, signs of respiratory disease were significantly fewer in the kittens vaccinated with the inactivated FVRCP vaccine compared with the ML FVRCP vaccine ( P = 0.005) during the period after inoculation when the majority of clinical disease was observed. Conclusions and relevance Parenteral administration of either the inactivated FVRCP vaccine or the ML FVRCP vaccine can decrease clinical signs of illness due to FHV-1 on a day 7 challenge when compared with controls. Use of either vaccine product is indicated in cats at risk of acute exposure to FHV-1.

  4. Clinical and economic impact of herpes zoster vaccination in elderly in Italy.

    Science.gov (United States)

    Boccalini, Sara; Alicino, Cristiano; Martinelli, Domenico; Bechini, Angela; Tiscione, Emilia; Pellizzari, Barbara; Prato, Rosa; Icardi, Giancarlo; Iannazzo, Stefania; Bonanni, Paolo

    2017-02-01

    Herpes zoster (HZ) is a very relevant pathology among elderly people (≥ 60 years of age), with a considerable disease burden and loss of quality of life. In the last years a new vaccine against HZ became available in Italy. Therefore, the Italian decision makers are now confronted with the decision whether that vaccination should be implemented. Pharmaco-economic analyses represent useful tools to value the feasibility of new immunization programs and their sustainability. To this aim, an ad hoc population model was developed in order to value the clinical and economic impact of HZ vaccination program for the elderly in Italy. Particularly, different immunization scenarios were modeled: vaccination of 60 years-old subjects (single cohort strategy), simultaneous vaccination of people aged 60 and 65 years (double cohort strategy) and, lastly, immunization of people aged 60, 65 and 70 years (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the first 5 years of the program. The mathematical model valued the clinical impact of vaccination on the number of HZ, post-herpetic neuralgia (PHN) and ophthalmic HZ. The results of the analysis show that, in Italy, a cohort-based HZ vaccination program in elderly could have a relevant impact on the reduction of clinical cases and a favorable economic profile for the National Health Service (NHS), as already foreseen in other countries. In addition, further benefits could be obtained when extending the study period beyond the 5-year horizon of our analysis.

  5. Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic

    Science.gov (United States)

    Asay, Garrett R. Beeler; Cho, Bo-Hyun; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    School nurses played a key role in Maine's school-located influenza vaccination (SLV) clinics during the 2009-2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent…

  6. Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine.

    Directory of Open Access Journals (Sweden)

    Paul E Makidon

    2008-08-01

    Full Text Available Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg in a novel nanoemulsion (NE adjuvant (HBsAg-NE could be effective with fewer administrations.Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6 titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu. Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2 subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability

  7. The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

    Science.gov (United States)

    Henao-Tamayo, Marcela; Shanley, Crystal A; Verma, Deepshikha; Zilavy, Andrew; Stapleton, Margaret C; Furney, Synthia K; Podell, Brendan; Orme, Ian M

    2015-01-01

    To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.

  8. The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marcela Henao-Tamayo

    Full Text Available To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.

  9. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    Science.gov (United States)

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

  10. Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era

    DEFF Research Database (Denmark)

    Pedersen, T.I.; Howitz, Michael Frantz; Andersen, Christian Østergaard

    2010-01-01

    P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults...... registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were 24 years old [median 62 years (range 25...

  11. Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial.

    Science.gov (United States)

    Rowland, Rosalind; Pathan, Ansar A; Satti, Iman; Poulton, Ian D; Matsumiya, Magali M L; Whittaker, Megan; Minassian, Angela M; O'Hara, Geraldine A; Hamill, Matthew; Scott, Janet T; Harris, Stephanie A; Poyntz, Hazel C; Bateman, Cynthia; Meyer, Joel; Williams, Nicola; Gilbert, Sarah C; Lawrie, Alison M; Hill, Adrian V S; McShane, Helen

    2013-01-01

    The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770.

  12. Promoting HPV Vaccination in Safety-Net Clinics: A Randomized Trial.

    Science.gov (United States)

    Tiro, Jasmin A; Sanders, Joanne M; Pruitt, Sandi L; Stevens, Clare Frey; Skinner, Celette Sugg; Bishop, Wendy P; Fuller, Sobha; Persaud, Donna

    2015-11-01

    Evaluate effects of a multicomponent intervention (human papillomavirus [HPV] vaccine-specific brochure and recalls) on HPV vaccination and secondarily examine if race/ethnicity moderates effects. Unvaccinated girls aged 11 to 18 years attending 4 safety-net pediatric clinics and their parent/guardian (n = 814 dyads) were randomized to (1) active comparison (general adolescent vaccine brochure), or (2) intervention consisting of a HPV vaccine-specific brochure, telephone recalls to parents who declined, and recalls to patients overdue for doses 2 and 3. HPV 1-dose and 3-dose coverages were assessed via electronic health records 12 months after randomization. Multivariate logistic regressions estimated adjusted odds and marginal predicted vaccine coverage by study arm and race/ethnicity. Intent-to-treat analyses found no main effect of the HPV vaccine-specific brochure on 1-dose coverage (42.0% vs 40.6%); however, secondary analyses found race/ethnicity was a significant moderator such that the intervention was effective only for Hispanic individuals (adjusted odds ratio [AOR] 1.43; 95% confidence interval [CI] 1.02-2.02), and not effective for black individuals (AOR 0.64; 95% CI 0.41-1.13). Recalls to parents who declined the vaccine during the index visit were not effective, but recalls to patients overdue for doses 2 and 3 were effective at increasing 3-dose coverage regardless of race/ethnicity (AOR 1.99; 95% CI 1.16-3.45). Educational materials describing only the HPV vaccine were effective for Hispanic but not black individuals. Future research should test mechanisms that may mediate intervention effects for different racial/ethnic groups, such as different informational needs or vaccine schemas (experiences, beliefs, norms). Copyright © 2015 by the American Academy of Pediatrics.

  13. Exploring evidence for behavioral risk compensation among participants in an HIV vaccine clinical trial.

    Science.gov (United States)

    Painter, Julia E; DiClemente, Ralph J; Jimenez, Lauren; Stuart, Theron; Sales, Jessica M; Mulligan, Mark J

    2017-06-16

    HIV vaccine trial participants may engage in behavioral risk compensation due to a false sense of protection. We conducted an ancillary study of an HIV Vaccine Trials Network (HVTN) vaccine efficacy trial to explore risk compensation among trial participants compared to persons who were willing to participate but ineligible based on previous exposure to the Ad5 virus (Ad5+) across three timepoints. Participants were drawn from the Atlanta, GA site of the HVTN 505 vaccine trial. From 2011-2013, all persons who met prescreening criteria for the clinical trial and presented for Ad5 antibody testing were invited to participate in the ancillary study. Data were collected from vaccine trial participants (n=51) and Ad5+ participants (n=60) via online surveys across three timepoints: baseline, T2 (after trial participants received 2/4 injections) and T3 (after trial participants received 4/4 injections). Data analyses assessed demographic, psychosocial, and behavioral differences at baseline and changes at each timepoint. At baseline, Ad5+ participants were less likely to have some college education (p=0.024) or health insurance (p=0.008), and were more likely to want to participate in the vaccine trial "to feel safer having unprotected sex" (p=0.005). Among vaccine trial participants, unprotected anal sex with a casual partner (p=0.05), HIV transmission worry (p=0.033), and perceived chance of getting HIV (p=0.027), decreased across timepoints. Study findings suggest that persons with previous exposure to Ad5 may be systematically different from their Ad5-negative peers. Unprotected anal sex with a casual partner significantly decreased among HIV vaccine trial participants, as did HIV worry and perceived chance of getting HIV. Findings did not support evidence of risk compensation among HIV vaccine trial participants compared to Ad5+ participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. HPV awareness and willingness to HPV vaccination among high-risk men attending an STI clinic in Puerto Rico.

    Science.gov (United States)

    Colón-López, Vivian; Del Toro-Mejías, Lizbeth M; Ortiz, Ana P; Tortolero-Luna, Guillermo; Palefsky, Joel M

    2012-12-01

    An HPV vaccine has been approved for men aged 9 to 26 in the US for the prevention of genital warts and anal cancer. The purpose of this study is to describe 1) HPV vaccine awareness, 2) willingness to get the HPV vaccine and 3) perceived susceptibility to HPV-related cancers and genital warts among men 18-26 years old who attend an STI clinic in San Juan, Puerto Rico (PR). A cross-sectional pilot study consisting of 206 HIV+/HIV- men. For purpose of this analysis, only those participants aged vaccinated against HPV. Fewer than a third knew about the HPV vaccine (28.3%). However, more than half (76.9%) were willing to be vaccinated against HPV. Information sources about the HPV vaccine included their female sexual partners (13.0%), a female sexual partner who received the vaccine (8.7%) and a male sexual partner (2.2%). Most participants'reported that the main reason that would increase their willingness to get vaccinated was if a physician recommend the vaccine (95.7%). Perceived susceptibility was low, particularly for anal and oral cancer. This pilot study shows poor awareness of the HPV vaccine, although willingness to getting the HPV vaccine was high among those who knew about the vaccine. Future studies should try to evaluate this paradox and study in depth willingness and barriers to vaccination among male sub-groups, such as men who have sex with men (MSM). These studies should also evaluate predictors of uptake of the HPV vaccine among men in this and other STI clinics in PR, in order to develop interventions to increase male vaccination.

  15. Comparison of functional assays used in the clinical development of a placental malaria vaccine

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Heno, Kristine Klysner; Adams, Yvonne

    2017-01-01

    BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria...... are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines. METHODS: The ability of sera from animals immunised with different VAR2CSA constructs to inhibit IE binding to CSA...

  16. Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Kumar, B Dinesh; Kumar, P Uday; Krishna, T Prasanna; Kalyanasundaram, S; Suresh, P; Jagadeesan, V; Hariharan, S; Naidu, A Nadamuni; Krishnaswamy, Kamala; Rangarajan, P N; Srinivasan, V A; Reddy, G S; Sesikeran, B

    2013-06-01

    Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28 th day. The information generated by this study not only draws attention to the need for national and international regulatory

  17. Pragmatic trial of an intervention to increase human papillomavirus vaccination in safety-net clinics

    Directory of Open Access Journals (Sweden)

    Maureen Sanderson

    2017-02-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection has been causally linked to six cancers, and many disproportionately affect minorties. This study reports on the development and effectiveness of an intervention aimed at increasing HPV vaccine uptake among African American and Hispanic pediatric patients in safety-net clinics. Methods Formative research, community engagement, and theory guided development of the intervention. A clustered, non-randomized controlled pragmatic trial was conducted in four clinics providing healthcare for the underserved in Tennessee, U.S., with two intervention sites and two usual care sites. Patients aged 9-18 years (N = 408 and their mothers (N = 305 enrolled, with children clustered within families. The intervention consisted of two provider/staff training sessions and provision of patient education materials, consisting of a video/flyer promoting HPV vaccine. Medical records were reviewed before/after the initial visit and after 12 months. Results At the initial visit, provision of patient education materials and provider recommendation were higher at intervention sites versus usual care sites, and receipt of HPV vaccine was higher at intervention sites (45.4% versus 32.9% but not significantly after adjusting for patient’s age and mother’s education. Provider recommendation, but not education materials, increased the likelihood of vaccine receipt at the initial visit, although over one-third of intervention mothers cited the flyer/video as motivating vaccination. Completion of the 3-dose series at follow-up was lower in the intervention arm. Conclusions Future interventions should combine patient education, intensive provider/staff education, and patient reminders. Research should compare patient education focusing on HPV vaccine only versus all adolescent vaccines. Trial registration Retrospectively registered with ClinicalTrials.gov NCT02808832 , 9/12/16

  18. DEVELOPMENT OF VACCINES BASED ON ADENOVIRAL VECTORS: A REVIEW OF FOREIGN CLINICAL STUDIES (PART 2

    Directory of Open Access Journals (Sweden)

    L. V. Cherenova

    2017-01-01

    Full Text Available Currently, many human infectious diseases do not developed effective methods of treatment and prevention. One of the latest successes of biotechnology is the use of adenoviral vectors carrying immunodominant antigens  of various pathogens as genetically engineered vaccines  both  preventive and therapeutic. The use of genetic  engineering technologies allows not  to use in the  manufacture of vaccines  live viruses and  bacteria, reduces  the  time  needed for vaccine  creation and  production of new vaccines.  Adenoviral vectors  naturally penetrate into human cells, causing a rather  long and significant  both humoral and cellular immune response. In the second  part of review, we provide  information about  the ongoing  worldwide  clinical  trials of adenoviral vector-based vaccines against various infectious diseases such as influenza, malaria, Ebola haemorrhagic fever, tuberculosis, hepatitis and  several others, like as to consider selection parameters of volunteers, vaccination schedule, doses of drug administration, results of completed experiments, and preliminary data  on currently ongoing  research.

  19. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies

    Directory of Open Access Journals (Sweden)

    Stefan eNiewiesk

    2014-09-01

    Full Text Available Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR with the Fcg receptor IIB (FcgRIIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2 signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing

  20. Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

    Science.gov (United States)

    Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

    2013-06-01

    Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at pimmunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  1. A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

    Directory of Open Access Journals (Sweden)

    Courtney L Davis

    Full Text Available We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS and O-membrane proteins (OMP were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1 the rate that Shigella migrates into the lamina propria or epithelium, 2 the rate that memory B cells (BM differentiate into antibody-secreting cells (ASC, 3 the rate at which antibodies are produced by activated ASC, and 4 the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

  2. Cervical, anal and oral HPV in an adolescent inner-city health clinic providing free vaccinations.

    Directory of Open Access Journals (Sweden)

    Nicolas F Schlecht

    Full Text Available Published human papillomavirus (HPV vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.The majority of subjects reported being of non-Caucasian (92% and/or Hispanic ethnicity (61%. Median age was 18 years (range:14-20. All had practiced vaginal sex, a third (33% practiced anal sex, and most (77% had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75, HPV16 (OR = 0.31, 95%CI:0.11-0.88 and HPV18 (OR = 0.14, 95%CI:0.03-0.75. For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72 and HPV18(OR = 0.12, 95%CI:0.01-1.16 were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20.HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites

  3. Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.

    Science.gov (United States)

    Poore, Elizabeth A; Slifka, Dawn K; Raué, Hans-Peter; Thomas, Archana; Hammarlund, Erika; Quintel, Benjamin K; Torrey, Lindsay L; Slifka, Ariel M; Richner, Justin M; Dubois, Melissa E; Johnson, Lawrence P; Diamond, Michael S; Slifka, Mark K; Amanna, Ian J

    2017-01-05

    West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. [BCG vaccination coverage in children born after the end of compulsory BCG vaccination and followed in maternal and child health clinics in France: a national survey 2009].

    Science.gov (United States)

    Guthmann, J-P; Fonteneau, L; Desplanques, L; Lévy-Bruhl, D

    2010-09-01

    Compulsory BCG vaccination was replaced in July 2007 by a strong recommendation to vaccinate children at high risk of tuberculosis. We measured BCG vaccination coverage (VC) in children for whom BCG is recommended, who were born after the end of compulsory BCG vaccination and are usually followed at Maternal and Child Health Clinics (MCHC). National sampling survey stratified by region and age group. Sample size was calculated in order to perform a separate analysis in Ile-de-France, region which has a specific vaccination policy and the highest tuberculosis incidence in mainland France. Children were selected through 2-stage random sampling in IDF and 3-stage random sampling outside IDF. They were recruited at the MCHC during the consultation where information was collected by the doctor through a structured questionnaire. BCG-VC was 89.8% (81.4-94.7) in IDF and 61.7% (53.8-69.0) outside IDF. In IDF, VC in children who had other criteria than solely residing in IDF was 92.4%. Outside IDF, children were on average vaccinated later than in IDF (i.e.: VC at the age of 3 months in children aged 2-12 months: 84% in IDF, 42% outside IDF). In both zones, children aged 2-12 months were vaccinated earlier compared to those aged >12 months. VC are high in children followed at MCHC in IDF, but can still be improved. They are insufficient in those followed at MCHC outside IDF where children are vaccinated too late. Efforts aimed at improving the dissemination of BCG vaccination recommendations and a better training of doctors in performing intradermal BCG vaccination could facilitate the implementation of this new BCG vaccination policy. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  5. Template protocol for clinical trials investigating vaccines Focus on safety elements

    OpenAIRE

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe

    2013-01-01

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts.

  6. Experimental Vaccine for Mosquito-Borne Chikungunya Virus Rates Well in Clinical Study | FNLCR

    Science.gov (United States)

    An experimental vaccine for mosquito-borne chikungunya virus, which spread to the U.S. this year, appears to be safe and well-tolerated while offering protection against the virus, according to the results of a first-in-human clinical trial. The vacc

  7. Proximity to safety-net clinics and HPV vaccine uptake among low-income, ethnic minority girls.

    Science.gov (United States)

    Tsui, Jennifer; Singhal, Rita; Rodriguez, Hector P; Gee, Gilbert C; Glenn, Beth A; Bastani, Roshan

    2013-04-12

    Human Papillomavirus (HPV) vaccine uptake remains low. Although publicly funded programs provide free or low cost vaccines to low-income children, barriers aside from cost may prevent disadvantaged girls from getting vaccinated. Prior studies have shown distance to health care as a potential barrier to utilizing pediatric preventive services. This study examines whether HPV vaccines are geographically accessible for low-income girls in Los Angeles County and whether proximity to safety-net clinics is associated with vaccine initiation. Interviews were conducted in multiple languages with largely immigrant, low-income mothers of girls ages 9 to 18 via a county health hotline to assess uptake and correlates of uptake. Addresses of respondents and safety-net clinics that provide the HPV vaccine for free or low cost were geo-coded and linked to create measures of geographic proximity. Logistic regression models were estimated for each proximity measure on HPV vaccine initiation while controlling for other factors. On average, 83% of the 468 girls had at least one clinic within 3-miles of their residence. The average travel time on public transportation to the nearest clinic among all girls was 21min. Average proximity to clinics differed significantly by race/ethnicity. Latinas had both the shortest travel distances (2.2 miles) and public transportation times (16min) compared to other racial/ethnic groups. The overall HPV vaccine initiation rate was 25%. Increased proximity to the nearest clinic was not significantly associated with initiation. By contrast, daughter's age and insurance status were significantly associated with increased uptake. This study is among the first to examine geographic access to HPV vaccines for underserved girls. Although the majority of girls live in close proximity to safety-net vaccination services, rates of initiation were low. Expanding clinic outreach in this urban area is likely more important than increasing geographic access to the

  8. Previous vaccination modifies both the clinical disease and immunological features in children with measles

    Directory of Open Access Journals (Sweden)

    Mitchell P

    2013-06-01

    Full Text Available INTRODUCTION: Measles that develops in previously vaccinated cases has been reported to be associated with modified disease, although severity has usually been assessed by the presence or absence of symptoms. To date no studies have attempted to subjectively grade the severity of the clinical features. AIM: To investigate both the objective and subjective severity of measles in vaccinated and unvaccinated cases in the context of a community outbreak. METHODS: A retrospective observational cohort study conducted in Christchurch in 2009 using notified data compared the presentation of measles in 14 confirmed cases that had received at least one MMR (measles, mumps, rubella vaccination and 14 age-matched unvaccinated confirmed cases. Additional details on the subjective and objective severity of the illness were obtained from parents/guardians using a standardised telephone questionnaire. RESULTS: The vaccinated group had significantly fewer clinical features on presentation (p=0.01, RR=1.3, 95% CI 1.1-1.6 and a less severe illness objectively, as measured by height and duration of fever, the number of days needing medication other than paracetamol and days required in bed. Unvaccinated cases were 2.8 times more likely to have more severe clinical features than vaccinated cases (OR=2.8, 95% CI 1.5-5.0. Unvaccinated cases were 3.0 times more likely to develop IgM antibody (RR=3.0, 95% CI 0.9-9.3. DISCUSSION: Previously vaccinated children who develop measles are likely to have less severe disease and serology results that may be inconclusive, particularly for IgM antibody if tested in the first few days after the rash onset.

  9. Effect of vaccination against sub-clinical Porcine Circovirus type 2 infection in a high-health finishing pig herd

    DEFF Research Database (Denmark)

    Nielsen, Gitte Blach; Nielsen, Jens Peter; Haugegaard, John

    2017-01-01

    the effect of vaccination against PCV2 in a sub-clinically infected, high-health finishing herd in terms of viral load in serum, feed conversion ratio and antimicrobial treatments. The study was conducted as a randomised clinical field trial with a parallel group design. Vaccination against PCV2...... significantly (p vaccinated group, as well as the viral load for positive pools from 5.79 to 3.99 log(10) copies per ml serum. Despite this, feed conversion ratio for the two groups were not significantly...... different with an average of 2.75 and 2.76 feeding units/kg gain for vaccinated and control pigs, respectively (p = 0.598). The proportion of pigs treated by injection with an antimicrobial was lower in the vaccinated group (4.4%) compared to the non-vaccinated group (5.6%), but the difference...

  10. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic.

    Science.gov (United States)

    Coller, Beth-Ann G; Blue, Jeffrey; Das, Rituparna; Dubey, Sheri; Finelli, Lynn; Gupta, Swati; Helmond, Frans; Grant-Klein, Rebecca J; Liu, Kenneth; Simon, Jakub; Troth, Sean; VanRheenen, Susan; Waterbury, Julie; Wivel, Ashley; Wolf, Jayanthi; Heppner, D Gray; Kemp, Tracy; Nichols, Rick; Monath, Thomas P

    2017-08-16

    The 2014-2016 Ebola outbreak caused over 28,000 cases and 11,000 deaths. Merck & Co. Inc., Kenilworth, NJ USA and NewLink Genetics are working with private and public partners to develop and license an Ebola vaccine that was evaluated extensively during the outbreak. The vaccine referred to as V920 is a recombinant vesicular stomatitis virus (rVSV) in which the VSV-G envelope glycoprotein (GP) is completely replaced by the Zaire ebolavirus GP (rVSVΔG-ZEBOV-GP). Eight Phase I and four Phase II/III clinical trials enrolling approximately 17,000 subjects were conducted in parallel to the outbreak to assess the safety, immunogenicity, and/or efficacy of V920. Immunogenicity data demonstrate that anti-GP antibodies are generally detectable by ELISA by 14days postvaccination with up to 100% seroconversion observed by 28days post dose. In addition, the results of a ring vaccination trial conducted by the WHO and their partners in Guinea suggest robust vaccine efficacy within 10days of receipt of a single dose of vaccine. The vaccine is generally well-tolerated when administered to healthy, non-pregnant adults. The development of this vaccine candidate in the context of this unprecedented epidemic has involved the close cooperation of large number of international partners and highlights what we as a public health community can accomplish when working together towards a common goal. Study identification: V920-001 to V920-012. CLINICALTRIALS.GOV identifiers: NCT02269423; NCT02280408; NCT02374385; NCT02314923; NCT02287480; NCT02283099; NCT02296983; NCT02344407; NCT02378753; NCT02503202. Copyright © 2017. Published by Elsevier Ltd.

  11. Review of tick-borne encephalitis and vaccines: clinical and economical aspects.

    Science.gov (United States)

    Šmit, Renata; Postma, Maarten J

    2015-05-01

    Tick-borne encephalitis (TBE) disease is an increasing burden not only locally but also globally. In most endemic countries, vaccination coverage is too low to reduce the TBE burden significantly; however, vaccination is the most effective protection against TBE, with various vaccines currently available. In spite of rising awareness of TBE, little attention is directed toward the health economics of the disease. The purpose of the present review is to compile information on TBE and its explicit clinical and economical aspects. Given the scarcity of studies, the authors conclude that more attention is needed for health economics of TBE. Notably, this would help establish guidance on efficient policies for TBE prevention, reduce disease burden and achieve population health benefits.

  12. Business Models, Vaccination Services, and Public Health Relationships of Retail Clinics: A Qualitative Study.

    Science.gov (United States)

    Arthur, Bayo C; Fisher, Allison Kennedy; Shoemaker, Sarah J; Pozniak, Alyssa; Stokley, Shannon

    2015-01-01

    Despite the rapid growth of retail clinics (RCs), literature is limited in terms of how these facilities offer preventive services, particularly vaccination services. The purpose of this study was to obtain an in-depth understanding of the RC business model pertaining to vaccine offerings, profitability, and decision making. From March to June 2009, we conducted 15 interviews with key individuals from three types of organizations: 12 representatives of RC corporations, 2 representatives of retail hosts (i.e., stores in which the RCs are located), and 1 representative of an industry association. We analyzed interview transcripts qualitatively. Our results indicate that consumer demand and profitability were the main drivers in offering vaccinations. RCs in this sample primarily offered vaccinations to adults and adolescents, and they were not well integrated with local public health and immunization registries. Our findings demonstrate the potential for stronger linkages with public health in these settings. The findings also may help inform future research to increase patient access to vaccination services at RCs.

  13. Key feasibility considerations when conducting vaccine clinical trials in Asia–Pacific countries

    Directory of Open Access Journals (Sweden)

    Lansang EZ

    2013-03-01

    Full Text Available Elvira Zenaida Lansang,1 Kenneth Tan,2 Saumya Nayak,1 Ken J Lee,1 Karen Wai1 1Feasibility and Site Identification – Asia, Quintiles East Asia Pte Ltd, Singapore; 2National University of Singapore, Singapore Introduction: Conducting clinical trial feasibility is an important first step in initiating a clinical trial. A robust feasibility process ensures that a realistic capability assessment is made before conducting a trial. A retrospective analysis of vaccine clinical trials was performed to understand changes which could affect feasibility recommendations. Methods: Feasibilities conducted by Quintiles between January 2011 and August 2012 were reviewed. Vaccine studies only involving Asia–Pacific countries were selected, and common study parameters were identified. Information from Quintiles’ database was retrieved to examine changes in parameters over time. Results: A total of six vaccine studies were identified within the 1.7-year period. Two studies were excluded because they did not contain feasibility information or had involved sites that were sponsor selected. Four studies were analyzed. Three cases required healthy volunteers, while one case involved a specific patient population. Age requirement and seasonality of disease mainly influenced recommendations for Study 1. Sponsor’s marketing strategy influenced the recommendations for Study 2. Study 3 showed the effect of a country’s immunization program and reimbursement of vaccines on a study’s success. In contrast to the other studies, Study 4 demonstrated the impact of eligibility criteria in recruitment recommendations for a vaccine trial requiring specific patient pools. Conclusion: Feasibility recommendations for vaccine trials are largely based on (1 eligibility criteria; (2 cultural beliefs; (3 country’s past recruitment performance; (4 use of advertising; (5 site’s access to subject populations; (6 cooperation with local health professionals and government; (7

  14. Current research and clinical trials for a vaccine against Chikungunya virus

    Directory of Open Access Journals (Sweden)

    Singh P

    2013-08-01

    Full Text Available Priyanka Singh,1 Mala Chhabra,1 Veena Mittal,1 Pankaj Sharma,1 Moshahid A Rizvi,2 Lakhvir Singh Chauhan,1 Arvind Rai1 1National Centre for Disease Control, Sham Nath Marg, 2Department of Biosciences, Jamia Millia Islamia, New Delhi, India Abstract: Chikungunya infection is a self-limiting Aedes mosquito-borne arboviral disease with variable clinical manifestations, ranging from asymptomatic illness to a very severe and crippling arthralgia. Until recently, Chikungunya was a little known disease that re-emerged in 2005–2006, leading to major outbreaks on the Indian Ocean Islands and in South East Asia, and eventually extending its range to temperate regions. It drew global attention due to its explosive onset, extensive geographic distribution, and high morbidity. Since re-emergence, an estimated one million symptomatic cases with 0.1% fatality per year have been reported globally. A lack of herd immunity, vector control, and globalization and trade are clearly a problem in the spread of this disease. The Chikungunya virus (CHIKV has also acquired biologically important mutations during its evolution, increasing its geographic reach. This disease has resulted in a loss of productivity in affected communities. The absence of a vaccine or an effective antiviral therapy makes dealing with this disease challenging for those involved in public health. There is an emergent need for an effective vaccine against CHIKV infection. The candidates that have been tested include attenuated living, nonliving and genetically engineered vaccines. Several of these vaccine candidates are in preclinical and clinical trials. This review outlines the current knowledge about chikungunya infection and vaccine development. Keywords: Chikungunya, outbreaks, epidemics, genotypes, vaccines, therapy

  15. Serologic response to inactivated poliovirus vaccine: a randomized clinical trial comparing 2 vaccination schedules in Puerto Rico.

    Science.gov (United States)

    Dayan, Gustavo H; Thorley, Margaret; Yamamura, Yasuhiro; Rodríguez, Nayra; McLaughlin, Steve; Torres, Lourdes M; Seda, Antonio; Carbia, Marcia; Alexander, Lorraine N; Caceres, Victor; Pallansch, Mark A

    2007-01-01

    The World Health Organization (WHO) recommends the discontinuation of oral poliovirus vaccine after eradication of wild poliovirus. Studies assessing inactivated poliovirus vaccine (IPV) immunogenicity in tropical countries, using the WHO Expanded Programme on Immunization (EPI) schedule, have been limited. We conducted a randomized clinical trial in Ponce, Puerto Rico. Infants were assigned to 1 of 2 study arms: those in the EPI arm received IPV at 6, 10, and 14 weeks of age, and those in the US arm received IPV at 2, 4, and 6 months of age. Neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested on serum specimens obtained before administration of the first dose of IPV and 28-45 days after administration of the last dose of IPV. Seroconversion rates for the EPI (n=225) and US (n=230) arms, respectively, were 85.8% and 99.6% for poliovirus type 1 (P<.001), 86.2% and 100% for poliovirus type 2 (P<.001), and 96.9% and 99.1% for poliovirus type 3 (P=.08). Seroconversion rates were lower among infants in the EPI arm who had high maternal antibody levels for all 3 poliovirus types (P<.001). The EPI schedule resulted in lower seroconversion rates for poliovirus types 1 and 2. These results are relevant for tropical countries planning to use IPV in a posteradication environment.

  16. Clinical and serological response of wild dogs (Lycaon pictus to vaccination against canine distemper, canine parvovirus infection and rabies

    Directory of Open Access Journals (Sweden)

    J. Van Heerden

    2002-07-01

    Full Text Available Wild dogs Lycaon pictus (n = 8 were vaccinated 4 times against canine distemper (n = 8 (initially with inactivated and subsequently with live attenuated strains of canine distemper and canine parvovirus infection (n = 8 over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

  17. Increased hepatitis C virus vaccine clinical trial literacy following a brief intervention among people who inject drugs

    NARCIS (Netherlands)

    White, Bethany; Madden, Annie; Hellard, Margaret; Kerr, Thomas; Prins, Maria; Page, Kimberly; Dore, Gregory J.; Maher, Lisa

    2013-01-01

    While people who inject drugs are at high risk of hepatitis C virus (HCV) infection and will be the target population for future HCV vaccine trials, little is known about clinical trial literacy (CTL) in this group. We assessed the impact of a brief intervention (BI) designed to improve HCV vaccine

  18. Behavioral and social science in HIV vaccine clinical research: Workshop report.

    Science.gov (United States)

    Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri

    2011-03-21

    In May 2009, a workshop was held in Washington DC to identify ways in which HIV vaccine clinical research could benefit from and better incorporate behavioral and social science (BSS) considerations. Seventy-one people from government, non-government, and private organizations participated, including HIV vaccine researchers, clinical trial scientists, BSS researchers, community representatives, and sponsors. This workshop elucidated the opportunities and challenges for integrating BSS in HIV vaccine research by highlighting insights gained from previous BSS research on HIV prevention and highlighting new BSS approaches and methodologies. Meeting participants identified priority areas where BSS methodologies could significantly impact HIV research and developed concrete recommendations for addressing current challenges encountered in HIV vaccine research relating to social impact, risk assessment, community engagement, informed consent, risk reduction, and special populations. These recommendations address the need for improving the accuracy of participant data; standardizing data collection to enable comparisons across studies; engaging the community at all levels; using evidenced-based counseling techniques; understanding the needs and concerns of target populations; and considering the impacts of macro-level forces and influences. The importance of establishing collaborations that can carry out these recommendations and facilitate necessary changes in thinking and practice was emphasized throughout the meeting. Copyright © 2011. Published by Elsevier Ltd.

  19. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

    Science.gov (United States)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-04-01

    Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

  20. Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond.

    Science.gov (United States)

    Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha

    2011-03-01

    In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin's lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages.

  1. Association of clinical signs and symptoms with pneumococcal acute otitis media by serotype--implications for vaccine effect.

    Science.gov (United States)

    Palmu, Arto A I; Jokinen, Jukka T; Kaijalainen, Tarja; Leinonen, Maija; Karma, Pekka; Kilpi, Terhi M

    2005-01-01

    Clinical symptoms and signs in acute otitis media (AOM) may differ depending on the various pneumococcal serotypes causing the disease. Alteration in clinical presentation of AOM could be expected after wide-scale pneumococcal vaccinations if there were considerable differences between vaccine serotypes and nonvaccine serotypes. In this study, data from 831 children in the control arm of the Finnish Otitis Media Vaccine Trial were used. The children were followed up prospectively in 8 study clinics from 2 to 24 months of age. If AOM was diagnosed, myringotomy was done, and middle ear fluid was aspirated for bacterial culture. Clinical symptoms and signs of AOM were routinely recorded on structured case report forms. Consistent with previous studies, 60% of pneumococcal episodes were caused by vaccine serotypes. There were no major differences between the clinical presentations of AOM due to different serotypes or serotype categories. However, earache was more often associated with AOM caused by vaccine and cross-reactive serotypes, compared with AOM caused by non-vaccine-related serotypes (42% vs. 29%; odds ratio, 1.66; 95% confidence interval, 1.02-2.70). Introduction of the currently available pneumococcal conjugate vaccine is unlikely to result in a remarkable alteration in the clinical presentation of pneumococcal AOM in infants.

  2. SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2010-01-01

    Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

  3. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

    Science.gov (United States)

    Durbin, Anna P.; Kirkpatrick, Beth D.; Pierce, Kristen K.; Schmidt, Alexander C.; Whitehead, Stephen S.

    2011-01-01

    The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LATV dengue vaccine. PMID:21781997

  4. An HTLV-I/II vaccine: from animal models to clinical trials?

    Science.gov (United States)

    de Thé, G; Kazanji, M

    1996-01-01

    A human T-lymphotropic virus type I/II (HTLV-I/II) vaccine is necessary in view of two etiologically related, life-threatening diseases, namely, adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. When the risk of developing autoimmune diseases such as uveitis, polymyositis, and arthritis is included, one can estimate the life-long risk of infected individuals to develop an HTLV associated pathology as approximately 10%. The populations at risk are, in a large majority, from developing countries but the epidemic of HTLV-II infection in intravenous drug users (IVDU) represents a possible reservoir for dissemination in the general population. The number of HTLV-I-infected individuals (15 to 25 million), together with the severity of associated disease, justifies the development of a vaccine. Different vaccine preparations have been developed, using mostly recombinant pox and adenoviruses, but DNA plasmid technology will soon become a feasible approach. Various animal models exist for experimental viral infections, involving rats, rabbits, or monkeys, but up to now, neither hematological nor neurological disorders have been induced by HTLV infection in such animal models. For long-term protection from HTLV-I-associated diseases, vaccination should induce both neutralizing antibodies and specific cell-mediated immunity. This will require the incorporation of both env and gag coding sequences in the vaccine preparations. Preventive clinical trials may involve different cohorts of seronegative young girls from endemic areas prior to sexual activity and IVDU in the industrialized world. In parallel, one should consider therapeutic vaccine trials in HTLV-I-positive mothers and IVDU to protect them against disease development. The observed rate of seroconversion in these different cohorts makes such trials feasible.

  5. Universal proposal strategies of anti-HPV vaccination for adolescents: comparative analysis between school-based and clinic immunization programs.

    Science.gov (United States)

    Desiante, F; Russo, C; Giorgino, A; Caputi, G; Battista, T; Cipriani, R; Conversano, M

    2017-09-01

    A promising approach to increase teenager's adherence to immunization against HPV is the administration of vaccinations within the school facilities. The Local Health Unit of Taranto experienced two different vaccine strategy proposals in the twelve-year-olds: the first one was the usual active call strategy in the outpatient clinic, while the second one provided the involvement of the schools in the area. The aim of the study is to evaluate the results of the proposed vaccination strategies in both sexes and in towns of different sizes in order to identify an effective path for achieving vaccine coverage improvement. To estimate the number of anti-HPV vaccine doses administered in adolescents of the 2003 cohort, we used the computerized vaccination system data of the Apulia Region. Then, once analyzed, the data for anti-HPV vaccine were broken down by gender, vaccine strategy and size of the town of residence. Analyses performed by using STATA SE 14. The multiple logistic regression points out that, females (OR = 3.2; p HPV vaccine cycle in adolescents. The comparative assessment of anti-HPV coverage strategies, suggests that school vaccination has resulted in significantly better outcomes than outpatient clinic one, for all the groups considered (overall 72.3% vs 55.6%). The involvement of school institutes can define a winning organizational model to get a wider adolescent's adherence to immunization programs, especially in bigger towns. The school vaccination strategy could improve anti-HPV vaccine adherence also in males, who perceives a lower HPV-related diseases risk than females.

  6. Pre-clinical and clinical development of the first placental malaria vaccine

    DEFF Research Database (Denmark)

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G

    2017-01-01

    Introduction: Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing...... the condition.  Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre...... will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine....

  7. NMOSD triggered by yellow fever vaccination - An unusual clinical presentation with segmental painful erythema.

    Science.gov (United States)

    Schöberl, F; Csanadi, E; Eren, O; Dieterich, M; Kümpfel, T

    2017-01-01

    Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Advanced Clinical Decision Support for Vaccine Adverse Event Detection and Reporting.

    Science.gov (United States)

    Baker, Meghan A; Kaelber, David C; Bar-Shain, David S; Moro, Pedro L; Zambarano, Bob; Mazza, Megan; Garcia, Crystal; Henry, Adam; Platt, Richard; Klompas, Michael

    2015-09-15

    Reporting of adverse events (AEs) following vaccination can help identify rare or unexpected complications of immunizations and aid in characterizing potential vaccine safety signals. We developed an open-source, generalizable clinical decision support system called Electronic Support for Public Health-Vaccine Adverse Event Reporting System (ESP-VAERS) to assist clinicians with AE detection and reporting. ESP-VAERS monitors patients' electronic health records for new diagnoses, changes in laboratory values, and new allergies following vaccinations. When suggestive events are found, ESP-VAERS sends the patient's clinician a secure electronic message with an invitation to affirm or refute the message, add comments, and submit an automated, prepopulated electronic report to VAERS. High-probability AEs are reported automatically if the clinician does not respond. We implemented ESP-VAERS in December 2012 throughout the MetroHealth System, an integrated healthcare system in Ohio. We queried the VAERS database to determine MetroHealth's baseline reporting rates from January 2009 to March 2012 and then assessed changes in reporting rates with ESP-VAERS. In the 8 months following implementation, 91 622 vaccinations were given. ESP-VAERS sent 1385 messages to responsible clinicians describing potential AEs. Clinicians opened 1304 (94.2%) messages, responded to 209 (15.1%), and confirmed 16 for transmission to VAERS. An additional 16 high-probability AEs were sent automatically. Reported events included seizure, pleural effusion, and lymphocytopenia. The odds of a VAERS report submission during the implementation period were 30.2 (95% confidence interval, 9.52-95.5) times greater than the odds during the comparable preimplementation period. An open-source, electronic health record-based clinical decision support system can increase AE detection and reporting rates in VAERS. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society

  9. The Recombinant Bacille Calmette–Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing

    Directory of Open Access Journals (Sweden)

    Natalie E. Nieuwenhuizen

    2017-09-01

    Full Text Available The only licensed vaccine against tuberculosis (TB, bacille Calmette–Guérin (BCG, protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔureC::hly (VPM1002 promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

  10. Template protocol for clinical trials investigating vaccines--focus on safety elements.

    Science.gov (United States)

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2013-11-12

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Record High US Measles Cases: Patient Vaccination, Clinical Assessment and Management

    Centers for Disease Control (CDC) Podcasts

    2014-06-30

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Record High US Measles Cases: Patient Vaccination, Clinical Assessment and Management. In May 2014, the United States recorded the largest number of reported measles cases since 1994 and the number continues to rise. Most cases reported have been acquired in the U.S. and are associated with importations from countries where measles is still common. This highly contagious, acute viral illness spreads quickly in unvaccinated populations once reaching the U.S. The recent measles outbreaks highlight the importance of maintaining high vaccination coverage in the U.S. and ensuring age-appropriate vaccination for international travelers. During this COCA call, clinicians will learn the status of measles in the U.S. and CDC vaccination recommendations and guidelines for patient assessment and management.  Created: 6/30/2014 by : National Center for Immunization and Respiratory Diseases; Division of Viral Diseases; Healthcare Preparedness Activity (HPA); Office of Public Health Preparedness and Response (OPHPR).   Date Released: 6/30/2014.

  12. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  13. A tool for the economic analysis of mass prophylaxis operations with an application to H1N1 influenza vaccination clinics.

    Science.gov (United States)

    Cho, Bo-Hyun; Hicks, Katherine A; Honeycutt, Amanda A; Hupert, Nathaniel; Khavjou, Olga; Messonnier, Mark; Washington, Michael L

    2011-01-01

    This article uses the 2009 H1N1 influenza vaccination program experience to introduce a cost analysis approach that may be relevant for planning mass prophylaxis operations, such as vaccination clinics at public health centers, work sites, schools, or pharmacy-based clinics. These costs are important for planning mass influenza vaccination activities and are relevant for all public health emergency preparedness scenarios requiring countermeasure dispensing. We demonstrate how costs vary depending on accounting perspective, staffing composition, and other factors. We also describe a mass vaccination clinic budgeting tool that clinic managers may use to estimate clinic costs and to examine how costs vary depending on the availability of volunteers or donated supplies and on the number of patients vaccinated per hour. Results from pilot tests with school-based H1N1 influenza vaccination clinic managers are described. The tool can also contribute to planning efforts for universal seasonal influenza vaccination.

  14. Clinical and immunological effects of Newcastle disease virus vaccine on bovine papillomatosis.

    Science.gov (United States)

    Avki, Sirri; Turutoglu, Hulya; Simsek, Atilla; Unsal, Ayhan

    2004-03-01

    Newcastle disease virus (NDV) has antineoplastic and immunostimulatory properties, and it is currently being clinically tested in anticancer therapy. In order to analyze the immunostimulatory effects of NDV on bovine papillomatosis, we inoculated 14 cows subcutaneously with an attenuated vaccine containing the LaSota strain of NDV (LS-NDV). Four cows with papillomatosis served as controls. Serum samples were collected from each animal 1 h before and, 7 and 21 days after inoculation. In inoculated cows, on days 7 and 21 the mean antibody titers were log2 2.43 +/- 0.92 and log2 5.57 +/- 0.72 by haemagglutination inhibition (HI), and the mean levels of tumor necrosis factor-alpha (TNF-alpha) were 5.80 +/- 4.19 and 5.39 +/- 2.66 ng/ml by WEHI-164 cytotoxicity assay. Significant differences between inoculated and control animals were evident for antibody titers on day 21 and clinical scores on day 60. A correlation was evident between the TNF-alpha activities and clinical scores on day 21. The clinical observations at day 60 showed that the papillomas in five cows were completely resolved (36%), one animal had no alterations on clinical appearance of the tumor (7%), and papillomas in eight cows were regressed (57%). In conclusion, these results demonstrated that inoculation of LS-NDV vaccine stimulates an antibody response and limited increase in TNF-alpha activity and may enhance clinical recovery in bovine papillomatosis.

  15. The clinical benefit and cost-effectiveness of human papillomavirus vaccination for adult women in the Netherlands.

    Science.gov (United States)

    Bogaards, Johannes A; Coupé, Veerle M H; Meijer, Chris J L M; Berkhof, Johannes

    2011-11-08

    The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17-25 years in 2010. The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status. In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17-25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status. The clinical benefit of HPV vaccination of women up to 25

  16. Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

    Science.gov (United States)

    Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

    2016-04-01

    Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Preclinical and clinical development of a YFV 17 D-based chimeric vaccine against West Nile virus.

    Science.gov (United States)

    Dayan, Gustavo H; Pugachev, Konstantin; Bevilacqua, Joan; Lang, Jean; Monath, Thomas P

    2013-12-09

    Substantial success has been achieved in the development and implementation of West Nile (WN) vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs) between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.

  18. Influence of simulated and actual community vaccination clinics on student empowerment and self-efficacy for public health nursing competencies.

    Science.gov (United States)

    Babenko-Mould, Yolanda; Ferguson, Karen; Riddell, Thelma; Hancock, Michele; Atthill, Stephanie

    2015-01-01

    To examine students' structural empowerment during simulated learning and actual nursing practice, and assess students' self-efficacy for public health nursing competencies (PHNC) after involvement in a mass influenza vaccination clinic as a community practice experience. A nonexperimental survey design was used with a sample of year three baccalaureate nursing students. Students completed a demographic form after the simulated clinic experience, they were assessed for perceptions of empowerment after being involved in the simulated and actual clinic settings, and self-efficacy was assessed after the actual clinic experience. Students perceived themselves as structurally empowered after completing the simulated and actual community vaccination clinics. Students reported a high level of self-efficacy for PHNC after their actual community vaccination clinic involvement. There was a significant correlation between empowerment and self-efficacy, which suggests that when students have access to empowering structures, they feel more confident to enact PHNC that align with practice in the clinics. This study suggests that nursing students acquired the necessary knowledge and skills for safe vaccination administration through the combination of simulated practice and participating in an actual public health vaccination clinic. © 2014 Wiley Periodicals, Inc.

  19. Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

    Directory of Open Access Journals (Sweden)

    Iole Macchia

    2013-01-01

    Full Text Available The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs and tumor-associated antigens (TAAs and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry- (FCM- based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

  20. Development of World Health Organization (WHO recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV vaccines

    Directory of Open Access Journals (Sweden)

    Malavika Prabhu

    2016-12-01

    Full Text Available The World Health Organization (WHO serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV vaccine as an example, we describe the process by which (1 a need to revise the guidelines was identified; (2 a group of stakeholders with complementary expertise and key questions were identified; (3 a scientific review was conducted; (4 consensus on revisions was achieved; (5 guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Keywords: HPV vaccine, WHO, Policy guidelines

  1. Factors influencing women's attitudes towards antenatal vaccines, group B Streptococcus and clinical trial participation in pregnancy: an online survey.

    Science.gov (United States)

    McQuaid, Fiona; Jones, Christine; Stevens, Zoe; Plumb, Jane; Hughes, Rhona; Bedford, Helen; Voysey, Merryn; Heath, Paul T; Snape, Matthew D

    2016-04-20

    To explore factors influencing the likelihood of antenatal vaccine acceptance of both routine UK antenatal vaccines (influenza and pertussis) and a hypothetical group B Streptococcus (GBS) vaccine in order to improve understanding of how to optimise antenatal immunisation acceptance, both in routine use and clinical trials. An online survey distributed to women of childbearing age in the UK. 1013 women aged 18-44 years in England, Scotland and Wales. Data from an online survey conducted to gauge the attitudes of 1013 women of childbearing age in England, Scotland and Wales to antenatal vaccination against GBS were further analysed to determine the influence of socioeconomic status, parity and age on attitudes to GBS immunisation, using attitudes to influenza and pertussis vaccines as reference immunisations. Factors influencing likelihood of participation in a hypothetical GBS vaccine trial were also assessed. Women with children were more likely to know about each of the 3 conditions surveyed (GBS: 45% vs 26%, pertussis: 79% vs 63%, influenza: 66% vs 54%), to accept vaccination (GBS: 77% vs 65%, pertussis: 79% vs 70%, influenza: 78% vs 68%) and to consider taking part in vaccine trials (37% vs 27% for a hypothetical GBS vaccine tested in 500 pregnant women). For GBS, giving information about the condition significantly increased the number of respondents who reported that they would be likely to receive the vaccine. Health professionals were the most important reported source of information. Increasing awareness about GBS, along with other key strategies, would be required to optimise the uptake of a routine vaccine, with a specific focus on informing women without previous children. More research specifically focusing on acceptability in pregnant women is required and, given the value attached to input from healthcare professionals, this group should be included in future studies. Published by the BMJ Publishing Group Limited. For permission to use (where not

  2. HPV Awareness and Vaccine Willingness Among Dominican Immigrant Parents Attending a Federal Qualified Health Clinic in Puerto Rico.

    Science.gov (United States)

    Colón-López, Vivian; Quiñones, Valerie; Del Toro-Mejías, Lizbeth M; Conde-Toro, Alexandra; Serra-Rivera, Michelle J; Martínez, Tania M; Rodríguez, Verónica; Berdiel, Luis; Villanueva, Héctor

    2015-08-01

    The purpose of this study was to describe the socio-demographic characteristics, awareness of human papillomavirus (HPV), and willingness to vaccinate among a convenience sample of 60 immigrant Dominican parents of adolescent sons in a Federal Qualified Health Clinic in Puerto Rico. Participation involved completing a self-administered survey. Even though more than half of the parents had not received proper HPV vaccine orientation from healthcare provider (58.3 %) nor asked provider for vaccination recommendation for their adolescent sons (56.7 %), most parents were aware of HPV (91.7 %) and HPV vaccination among males (55.0 %). Among those with unvaccinated sons, willingness to vaccinate the son within the next year was high (83.8 %). The low vaccination percentage (31.7 %) and information exchange between the parents and the son's healthcare provider indicates an opportunity for future culturally tailored interventions to target HPV vaccination among healthcare providers and parents of foreign descent in order to increase HPV vaccine uptake among males.

  3. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype...

  4. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma - A clinical, phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, A.; Trepiakas, R.; Wenandy, L.

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC- based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype...

  5. Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial

    DEFF Research Database (Denmark)

    Fröbert, Ole; Götberg, Matthias; Angerås, Oskar

    2017-01-01

    BACKGROUND: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following...... influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. METHODS/DESIGN: The Influenza...... vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly...

  6. Clinical efficacy of trivalent oral poliomyelitis vaccine: a case-control study.

    Science.gov (United States)

    Deivanayagam, N.; Nedunchelian, K.; Ahamed, S. S.; Rathnam, S. R.

    1993-01-01

    A case-control study was carried out between May 1988 and May 1989 to assess the effectiveness of three doses of trivalent oral poliomyelitis vaccine (TOPV3) in children aged 6-35 months in Madras city. All the cases were patients with acute paralytic poliomyelitis who were residing in Madras city and were hospitalized in the Institute of Child Health; they represented 95% of such cases in the city. The diagnosis was based on clinical grounds and confirmed by stool culture which was positive in 60%. Age- and sex-matched controls, all residing in the city of Madras, were recruited concurrently from the Institute's outpatient department. There were 78 cases and 315 controls. Vaccine efficacy observed for TOPV3 was 81% (95% CI, 58-91%) for the 6-35-month age group and 86% (95% CI, 67-94%) for the 6-23-month age group. Vaccine efficacy, after controlling for age using the Mantel-Haenszel method, was 83% (95% CI, 67-91%). An unimmunized child was at 5 times greater risk of developing acute paralytic poliomyelitis than a fully immunized child. PMID:8324848

  7. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  8. Resurgence of pertussis at the age of vaccination: clinical, epidemiological, and molecular aspects

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    Rosângela S.L.A. Torres

    2015-08-01

    Full Text Available OBJECTIVE: Report the incidence, epidemiology, clinical features, death, and vaccination status of patients with whooping cough and perform genotypic characterization of isolates of B. pertussis identified in the state of Paraná, during January 2007 to December 2013.METHODS: Cross-sectional study including 1,209 patients with pertussis. Data were obtained through the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação - SINAN and molecular epidemiology was performed by repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab(r, bioMerieux, France.RESULTS: The incidence of pertussis in the state of Paraná increased sharply from 0.15-0.76 per 100,000 habitants between 2007-2010 to 1.7-4.28 per 100,000 between 2011-2013. Patients with less than 1 year of age were more stricken (67.5%. Fifty-nine children (5% developed pertussis even after receiving three doses and two diphtheria-tetanus-pertussis (DTP boosters vaccine. The most common complications were pneumonia (14.5%, otitis (0.9%, and encephalopathy (0.7%. Isolates of B. pertussis were grouped into two groups (G1 and G2 and eight distinct patterns (G1: P1-P5 and G2: P6-P8.CONCLUSION: The resurgence of pertussis should stimulate new research to develop vaccines with greater capacity of protection against current clones and also encourage implementation of new strategies for vaccination in order to reduce the risk of disease in infants.

  9. Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial.

    Science.gov (United States)

    Jamshed, Saad; Walsh, Edward E; Dimitroff, Lynda J; Santelli, Jeanine Seguin; Falsey, Ann R

    2016-01-27

    Patients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy. This double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates. A total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups. Trivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population. This study was registered at ClinicalTrials.gov as NCT01666782. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. CLINICAL AND IMMUNOLOGICAL ASPECTS OF T C ELL-BASED VACCINE THERAPY IN PATIENTS WITH PROGREDIENT MULTIPLE SCLEROSIS

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    G. Seledtsova

    2012-01-01

    Full Text Available Abstract. Thirty-nine patients with a progredient clinical form of chronic multiple sclerosis (MS were subject to multiple immunization with autologous polyclonal T-cell vaccines. Two years after initiating the vaccine therapy, no evidence for disease progression was noted in 16 patients (41% of total. Neurological improvement was observed in five cases (13% from the vaccine-treated group. Of 22 control MS patients who did not receive the immunotherapy, only 6 persons (27% exhibited stabilization of their clinical state. Clinical improvement was not detectable among this group of MS patients. A group of twenty-six MS patients was treated with Rebif, without evidence of disease progression in eleven cases (42%, and distinct neurological improvement noted in one patient (4% from this group. One year after starting the vaccine therapy, a rise in serum IL-10 was detected in vaccine-treated patients, whereas IL-17 and IL-18 serum levels remained within the initial ranges. A correlation between the serum levels of anti-myelin antibodies and appropriate anti-idiotypic antibodies was revealed in these patients. In general, the results obtained suggest polyclonal T-cell vaccination as a potentially effective treatment approach, both at early and more advanced stages of the disorder.

  11. Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial.

    Science.gov (United States)

    Mulligan, Mark J; Stapleton, Jack T; Keitel, Wendy A; Frey, Sharon E; Chen, Wilbur H; Rouphael, Nadine; Edupuganti, Srilatha; Beck, Allison; Winokur, Patricia L; El Sahly, Hana M; Patel, Shital M; Atmar, Robert L; Graham, Irene; Anderson, Edwin; El-Kamary, Samer S; Pasetti, Marcela F; Sztein, Marcelo B; Hill, Heather; Goll, Johannes B

    2017-08-24

    Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was -6.9% (-16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001). The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695. Copyright © 2017 The Authors. Published by Elsevier

  12. Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Asanuma Hiroko

    2008-05-01

    Full Text Available Abstract Background We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. Methods We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. Results In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1, and another had general malaise (grade 1 and fever (grade 1. Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD. Immunologically, in 3 of the 10 patients (30%, an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%, although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. Conclusion This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more

  13. Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

    Science.gov (United States)

    Clemens, John

    2011-01-01

    Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries. PMID:21893543

  14. Costs of School-Located Influenza Vaccination Clinics in Maine during the 2009-2010 H1N1 Pandemic

    Science.gov (United States)

    Cho, Bo-Hyun; Asay, Garrett R. Beeler; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    This study retrospectively estimated costs for a convenience sample of school-located vaccination (SLV) clinics conducted in Maine during the 2009-2010 influenza season. Surveys were developed to capture the cost of labor including unpaid volunteers as well as supplies and materials used in SLV clinics. Six nurses from different school districts…

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

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    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.

  16. Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial.

    Science.gov (United States)

    Thøstesen, L M; Kjaergaard, J; Pihl, G T; Birk, N M; Nissen, T N; Aaby, P; Jensen, A K G; Olesen, A W; Stensballe, L G; Jeppesen, D L; Benn, C S; Kofoed, P-E

    2017-09-20

    Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age clinical examinations until 13 months. Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76). © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  17. Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three Swiss Travel Clinics.

    Science.gov (United States)

    Huber, Fabienne; Ehrensperger, Benoît; Hatz, Christoph; Chappuis, François; Bühler, Silja; Eperon, Gilles

    2018-01-01

    Patients increasingly benefit from immunosuppressive/immunomodulatory medications for a range of conditions allowing them a lifestyle similar to healthy individuals, including travel. However, the administration of live vaccines to immunodeficient patients bears the risk of replication of the attenuated vaccine microorganism. Therefore, live vaccines are generally contraindicated on immunosuppression. Data on live vaccinations on immunosuppressive/immunomodulatory medication are scarce. We identified all travellers seeking pre-travel advice in three Swiss travel clinics with a live vaccine during immunosuppressive/immunomodulatory therapy to ascertain experienced side effects. A retrospective and multi-centre study design was chosen to increase the sample size. This study was conducted in the travel clinics of the University of Zurich; the Swiss TPH, Basel; and Geneva University Hospitals. Travellers on immunosuppressive/immunomodulatory therapy who received live vaccines [yellow fever vaccination (YFV), measles/mumps/rubella (MMR), varicella and/ or oral typhoid vaccination (OTV)] between 2008 and 2015 were identified and interviewed. A total of 60 age- and sex-matched controls (matched to Basel/Zurich travel clinics travellers) were included. Overall, 197 patients were identified. And 116 patients (59%) and 60 controls were interviewed. YFV was administered 92 times, MMR 21 times, varicella 4 times and OTV 6 times to patients on immunosuppressive/immunomodulatory therapy. Most common medications were corticosteroids (n = 45), mesalazine (n = 28) and methotrexate (n = 19). Live vaccines were also administered on biological treatment, e.g. TNF-alpha inhibitors (n = 8). Systemic reactions were observed in 12.2% of the immunosuppressed vs 13.3% of controls; local reactions in 7.8% of the immunosuppressed vs 11.7% of controls. In controls, all reactions were mild/moderate. In the immunosuppressed, 2/21 severe reactions occurred: severe local pain on interferon

  18. The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

    Science.gov (United States)

    Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

    2016-09-01

    Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

  19. A new multivalent (DHPPi/L4R) canine combination vaccine prevents infection, shedding and clinical signs following experimental challenge with four Leptospira serovars.

    Science.gov (United States)

    Wilson, Stephen; Stirling, Catrina; Thomas, Anne; King, Vickie; Plevová, Edita; Chromá, Ludmila; Siedek, Elisabeth; Illambas, Joanna; Salt, Jeremy; Sture, Gordon

    2013-06-28

    Although effective vaccines have been developed against the common Leptospira serovars, they are still reported in clinical cases, while others are increasingly prevalent. The results from four challenge studies following vaccination of dogs with a new combination vaccine (DHPPi/L4R) containing inactivated L. serovars, L. canicola, L. icterohaemorrhagiae, L. bratislava and L. grippotyphosa conducted to satisfy the requirements of the European Pharmacopoeia monograph (01/2008:0447), are reported. Six week old dogs received two vaccinations, three weeks apart, and were challenged 25 days later with different isolates of the L. serovars. Clinical observations were recorded, and blood, urine and tissue samples were collected for analysis. Following challenge, non-vaccinated dogs demonstrated various clinical signs, while no vaccinated dogs were affected; significant differences in mean clinical scores were observed. Measurable antibody titres to each Leptospira antigen were seen in vaccinated dogs 21 days following the first vaccination, with further increases in antibody titres observed following challenge with the respective Leptospira strain. Non-vaccinated dogs remained seronegative until challenge. Leptospira were re-isolated from the blood, urine, kidney and liver of all non-vaccinated dogs following challenge. In contrast no vaccinated dogs had Leptospira re-isolated from the same tissues. Significant differences were seen in number of days with positive isolation (blood and urine) and in number of dogs with positive samples (kidney and liver). In conclusion, vaccination of dogs with the new vaccine induces protective immunity 25 days after second vaccination with protection against infection, renal infection and clinical signs following challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica.

    Science.gov (United States)

    García-Sellés, J; Pascual, A; Funes, E; Pagán, J A; López, J-D; Negro, J M; Hernández, J

    2003-01-01

    The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen.

  1. EFFICIENCY OF INFLUENZA VACCINATION IN PATIENTS WITH CIRCULATORY SYSTEM DISEASES UNDER DISPENSARY OBSERVATION IN OUTPATIENT CLINICS: PROSPECTIVE FOLLOW-UP MONITORING DATA

    Directory of Open Access Journals (Sweden)

    S. A. Boytsov

    2016-01-01

    Full Text Available Aim. To estimate an efficiency of influenza vaccination in patients with circulatory system diseases diseases (CSD under 3-year follow-up in outpatient clinics.Methods. The efficiency of influenza vaccination was investigated in CSD patients followed up at 2Ivanovo outpatient clinics and 2Saratov ones. The investigation enrolled 817 people, including 367 patients who consented to Grippol Plus influenza vaccination and 450 who refused.Results. During 36-month follow-up after being included in the study the vaccinated group showed a significantly fewer influenza and acute respiratory viral infections than the non-vaccinated group (28 and 442; р<0.0001. The vaccinated group had fewer CSD worsening cases per patient (p=0.04 and CSD-associated hospitalization rates (p=0.006 than the non-vaccinated group. In the vaccinated group, the total number of cases of cerebral stroke, myocardial infarction, deaths from cardiovascular diseases (CVD was significantly less (17 compared with non-vaccinated (38, р=0.03. The risk of infectious diseases and acute cardiovascular event (myocardial infarction, stroke, death from CVD was significantly lower in the group of vaccinated patients: by 36% (p=0.001 and by 59% (p=0.008, respectively.Conclusion. Influenza vaccination, as an essential component of complex medical prevention, leads to reduction in incidence of infectious diseases and of CSD worsening including myocardial infarction, stroke, and death from CVD in patients under 3-year monitoring in outpatient clinics

  2. A Phase-1 Clinical Trial of a DNA Vaccine for Venezuelan Equine Encephalitis Delivered by Intramuscular or Intradermal Electroporation

    Science.gov (United States)

    2016-05-25

    concerns associated with pWRG/VEE or delivery method identified during the Phase 1 study. 3.4. Tolerability of Vaccine Procedures To assess the...results of the Phase I clinical study of EP-mediated pWRG/VEE delivery demonstrate an acceptable safety and reactogenicity profile for the DNA vaccine...11] Hooper JW, Moon JE, Paolino KM, Newcomer R, McLain DE, Josleyn M, et al. A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment

  3. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial.

    Science.gov (United States)

    Grode, Leander; Ganoza, Christian A; Brohm, Christiane; Weiner, January; Eisele, Bernd; Kaufmann, Stefan H E

    2013-02-18

    Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034). Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG ΔureC::hly Hm(R)) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens. Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, n=40 and BCG-immune, n=40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals. VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Travellers' profile, travel patterns and vaccine practices--a 10-year prospective study in a Swiss Travel Clinic.

    Science.gov (United States)

    Boubaker, Rim; Meige, Pierrette; Mialet, Catherine; Buffat, Chantal Ngarambe; Uwanyiligira, Mediatrice; Widmer, Francine; Rochat, Jacynthe; Fossati, Annie Hérard; Souvannaraj-Blanchant, Manisinh; Payot, Sylvie; Rochat, Laurence; de Vallière, Serge; Genton, Blaise; D'Acremont, Valérie

    2016-01-01

    The travel clinic in Lausanne serves a catchment area of 700 000 of inhabitants and provides pre- and post-travel consultations. This study describes the profile of attendees before departure, their travel patterns and the travel clinic practices in terms of vaccination over time. We included all pre-travel first consultation data recorded between November 2002 and December 2012 by a custom-made program DIAMM/G. We analysed client profiles, travel characteristics and vaccinations prescribed over time. Sixty-five thousand and forty-six client-trips were recorded. Fifty-one percent clients were female. Mean age was 32 years. In total, 0.1% were aged Latin America and 1% (each) to Oceania and Europe; 19% visited more than one country. India was the most common destination (9.6% of travellers) followed by Thailand (8.6%) and Kenya (6.4%). Seventy-three percent of travellers were planning to travel for ≤ 4 weeks. The main reasons for travel were tourism (75%) and visiting friends and relatives (18%). Sixteen percent were backpackers. Pre-travel advice were sought a median of 29 days before departure. Ninety-nine percent received vaccine(s). The most frequently administered vaccines were hepatitis A (53%), tetanus-diphtheria (46%), yellow fever (39%), poliomyelitis (38%) and typhoid fever (30%). The profile of travel clinic attendees was younger than the general Swiss population. A significant proportion of travellers received vaccinations that are recommended in the routine national programme. These findings highlight the important role of travel clinics to (i) take care of an age group that has little contact with general practitioners and (ii) update vaccination status. The most commonly prescribed travel-related vaccines were for hepatitis A and yellow fever. The question remains to know whether clients do attend travel clinics because of compulsory vaccinations or because of real travel health concern or both. © International Society of Travel Medicine, 2016

  5. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  6. Next-generation outer membrane vesicle vaccines from concept to clinical trials

    NARCIS (Netherlands)

    Waterbeemd, van de B.

    2013-01-01

    Only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. The OMV vaccines, however, provide limited coverage and are difficult to produce. This is caused by an obligatory detergent treatment, which removes lipopolysaccharide

  7. A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation.

    Science.gov (United States)

    Hooper, J W; Moon, J E; Paolino, K M; Newcomer, R; McLain, D E; Josleyn, M; Hannaman, D; Schmaljohn, C

    2014-05-01

    Haemorrhagic fever with renal syndrome (HFRS) is endemic in Asia, Europe and Scandinavia, and is caused by infection with the hantaviruses Hantaan (HTNV), Seoul (SEOV), Puumala (PUUV), or Dobrava (DOBV) viruses. We developed candidate DNA vaccines for HFRS expressing the Gn and Gc genes of HTNV or PUUV and evaluated them in an open-label, single-centre Phase 1 study. Three groups of nine participants each were vaccinated on days 0, 28 and 56 with the DNA vaccines for HTNV, PUUV, or a mixture of both vaccines using the Ichor Medical Systems TriGrid Intramuscular Delivery System. All vaccinations consisted of a total dose of 2.0 mg DNA in an injected volume of 1 mL saline. For the combined vaccine, the mixture contained equal amounts (1.0 mg) of each DNA vaccine. There were no study-related serious adverse events. Neutralizing antibody responses were measured by a plaque reduction neutralization test. Neutralizing antibody responses were detected in five of nine and seven of nine individuals who completed all three vaccinations with the HTNV or PUUV DNA vaccines, respectively. In the combined vaccine group, seven of the nine volunteers receiving all three vaccinations developed neutralizing antibodies to PUUV. The three strongest responders to the PUUV vaccine also had strong neutralizing antibody responses to HTNV. These results demonstrate that the HTNV and PUUV DNA vaccines delivered by electroporation separately or as a mixture are safe. In addition, both vaccines were immunogenic, although when mixed together, more participants responded to the PUUV than to the HTNV DNA vaccine. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  8. New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development

    NARCIS (Netherlands)

    Kamath, A.T.; Fruth, U.; Brennan, M.; Dobbelaer, R.; Hubrechts, P.; Ho, M.M.; Mayner, R.E.; Thole, J.E.R.; Walker, K.B.; Liu, C.M.; Lambert, P.H.

    2005-01-01

    As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A

  9. Review of tick-borne encephalitis and vaccines : clinical and economical aspects

    NARCIS (Netherlands)

    Smit, Renata; Postma, Maarten J

    Tick-borne encephalitis (TBE) disease is an increasing burden not only locally but also globally. In most endemic countries, vaccination coverage is too low to reduce the TBE burden significantly; however, vaccination is the most effective protection against TBE, with various vaccines currently

  10. Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

    Science.gov (United States)

    Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

    2017-04-01

    Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    vaccinations. Seven patients remained in stable disease (SD) three months after the first vac- cination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

  12. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis...

  13. Comparison of functional assays used in the clinical development of a placental malaria vaccine.

    Science.gov (United States)

    Pehrson, Caroline; Heno, Kristine K; Adams, Yvonne; Resende, Mafalda; Mathiesen, Line; Soegaard, Max; de Jongh, Willem A; Theander, Thor G; Salanti, Ali; Nielsen, Morten A

    2017-01-23

    Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines. The ability of sera from animals immunised with different VAR2CSA constructs to inhibit IE binding to CSA was investigated in three in vitro assays using 96-well plates, petri dishes, capillary flow and an ex vivo placental perfusion assay. The inter-assay variation was not uniform between assays and ranged from above ten-fold in the flow assay to two-fold in the perfusion assay. The intra-assay variation was highest in the petri dish assay. A positive correlation between IE binding avidity and the level of binding after antibody inhibition in the petri dish assay indicate that high avidity IE binding is more difficult to inhibit. The highest binding inhibition sensitivity was found in the 96-well and petri dish assays compared to the flow and perfusion assays where binding inhibition required higher antibody titers. The inhibitory capacity of antibodies is not easily translated between assays and the high sensitivity of the 96-well and petri dish assays stresses the need for comparing serial dilutions of serum. Furthermore, IE binding avidity must be in the same range when comparing data from different days. There was an overall concordance in the capacity of antibody-mediated inhibition, when comparing the in vitro assays with the perfusion assay, which more closely represents in vivo conditions. Importantly the ID1-ID2a protein in a liposomal formulation, currently in a phase I trial, effectively induced antibodies that inhibited IE adhesion in placental tissue. Copyright © 2016

  14. Validating child vaccination status in a demographic surveillance system using data from a clinical cohort study: evidence from rural South Africa.

    Science.gov (United States)

    Ndirangu, James; Bland, Ruth; Bärnighausen, Till; Newell, Marie-Louise

    2011-05-23

    Childhood vaccination coverage can be estimated from a range of sources. This study aims to validate vaccination data from a longitudinal population-based demographic surveillance system (DSS) against data from a clinical cohort study. The sample includes 821 children in the Vertical Transmission cohort Study (VTS), who were born between December 2001 and April 2005, and were matched to the Africa Centre DSS, in northern KwaZulu-Natal. Vaccination information in the surveillance was collected retrospectively, using standardized questionnaires during bi-annual household visits, when the child was 12 to 23 months of age. DSS vaccination information was based on extraction from a vaccination card or, if the card was not available, on maternal recall. In the VTS, vaccination data was collected at scheduled maternal and child clinic visits when a study nurse administered child vaccinations. We estimated the sensitivity of the surveillance in detecting vaccinations conducted as part of the VTS during these clinic visits. Vaccination data in matched children in the DSS was based on the vaccination card in about two-thirds of the cases and on maternal recall in about one-third. The sensitivity of the vaccination variables in the surveillance was high for all vaccines based on either information from a South African Road-to-Health (RTH) card (0.94-0.97) or maternal recall (0.94-0.98). Addition of maternal recall to the RTH card information had little effect on the sensitivity of the surveillance variable (0.95-0.97). The estimates of sensitivity did not vary significantly, when we stratified the analyses by maternal antenatal HIV status. Addition of maternal recall of vaccination status of the child to the RTH card information significantly increased the proportion of children known to be vaccinated across all vaccines in the DSS. Maternal recall performs well in identifying vaccinated children aged 12-23 months (both in HIV-infected and HIV-uninfected mothers), with

  15. Third-generation smallpox vaccines: challenges in the absence of clinical smallpox.

    Science.gov (United States)

    Meseda, Clement A; Weir, Jerry P

    2010-09-01

    Smallpox, a disease caused by variola virus, is estimated to have killed hundreds of millions to billions of people before it was certified as eradicated in 1980. However, there has been renewed interest in smallpox vaccine development due in part to zoonotic poxvirus infections and the possibility of a re-emergence of smallpox, as well as the fact that first-generation smallpox vaccines are associated with relatively rare, but severe, adverse reactions in some vaccinees. An understanding of the immune mechanisms of vaccine protection and the use of suitable animal models for vaccine efficacy assessment are paramount to the development of safer and effective smallpox vaccines. This article focuses on studies aimed at understanding the immune responses elicited by vaccinia virus and the various animal models that can be used to evaluate smallpox vaccine efficacy. Harnessing this information is necessary to assess the effectiveness and potential usefulness of new-generation smallpox vaccines.

  16. Views on HPV and HPV Vaccination: The Experience at a Federal Qualified Clinic in Puerto Rico.

    Science.gov (United States)

    Colón-López, Vivian; Toro-Mejías, Lizbeth M; Conde-Toro, Alexandra; Serra-Rivera, Michelle J; Martínez, Tania M; Rodríguez, Verónica; Ríos, Ana M; Berdiel, Luis; Villanueva, Héctor

    2016-01-01

    The purpose of this study was to understand through a quantitative assessment, the views of HPV and HPV vaccination among parents of sons from a FQHC in PR. A self-administered questionnaire was given to a convenience sample of 200 parents of sons 9-17 years old. Nearly 30% of the parents reported that their sons had initiated the HPV vaccine regimen. Health care provider recommendation was significantly associated with vaccine initiation. Among parents of unvaccinated sons, the main reason for not getting the HPV vaccine was they did not know that boys were allowed to get the vaccine. Future efforts should focus on multilevel interventions aimed to increase knowledge as well as other modified behavioral determinants in parents of young males about HPV and the vaccine. Capacity building efforts should be targeted also to increase health providers' education and communication skills to promote HPV vaccination effectively.

  17. A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus.

    Directory of Open Access Journals (Sweden)

    Courtney Waugh

    Full Text Available Diseases associated with Chlamydia pecorum infection are a major cause of decline in koala populations in Australia. While koalas in care can generally be treated, a vaccine is considered the only option to effectively reduce the threat of infection and disease at the population level. In the current study, we vaccinated 30 free-ranging koalas with a prototype Chlamydia pecorum vaccine consisting of a recombinant chlamydial MOMP adjuvanted with an immune stimulating complex. An additional cohort of 30 animals did not receive any vaccine and acted as comparison controls. Animals accepted into this study were either uninfected (Chlamydia PCR negative at time of initial vaccination, or infected (C. pecorum positive at either urogenital (UGT and/or ocular sites (Oc, but with no clinical signs of chlamydial disease. All koalas were vaccinated/sampled and then re-released into their natural habitat before re-capturing and re-sampling at 6 and 12 months. All vaccinated koalas produced a strong immune response to the vaccine, as indicated by high titres of specific plasma antibodies. The incidence of new infections in vaccinated koalas over the 12-month period post-vaccination was slightly less than koalas in the control group, however, this was not statistically significant. Importantly though, the vaccine was able to significantly reduce the infectious load in animals that were Chlamydia positive at the time of vaccination. This effect was evident at both the Oc and UGT sites and was stronger at 6 months than at 12 months post-vaccination. Finally, the vaccine was also able to reduce the number of animals that progressed to disease during the 12-month period. While the sample sizes were small (statistically speaking, results were nonetheless striking. This study highlights the potential for successful development of a Chlamydia vaccine for koalas in a wild setting.

  18. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors.

    Science.gov (United States)

    Woestenberg, Petra J; King, Audrey J; van der Sande, Marianne A B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; Hoebe, Christian J P A; Bogaards, Johannes A; van Benthem, Birgit H B

    2017-04-01

    Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results. We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Effect of emergency FMD vaccine antigen payload on protection, sub-clinical infection and persistence following direct contact challenge of cattle.

    Science.gov (United States)

    Cox, S J; Voyce, C; Parida, S; Reid, S M; Hamblin, P A; Hutchings, G; Paton, D J; Barnett, P V

    2006-04-12

    Previous work, in sheep vaccinated with emergency foot-and-mouth disease (FMD) vaccine, indicated the benefit of increasing the antigen payload in inhibiting local virus replication and consequently persistence following an indirect aerosol challenge with a virus homologous to the vaccine strain. The work presented here investigates this possibility further using cattle and a more severe semi-heterologous direct contact challenge. The quantitative dynamics of virus replication and excretion in both vaccinated and non-vaccinated cattle following challenge are examined. Two experiments were carried out each involving 20 vaccinated and 5 non-vaccinated cattle. An O(1) Manisa vaccine (18 PD(50)) was used for the first, previously reported experiment [Cox SJ, Voyce C, Parida S, Reid SM, Hamblin PA, Paton DJ, et al. Protection against direct contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx. Vaccine 2005;23:1106-13]. The same vaccine was used for the second experiment described in this paper except the antigen payload was increased 10-fold per bovine dose, resulting in significantly higher FMD virus neutralising antibody titres prior to challenge. Twenty-one days post-vaccination the cattle received a 5-day direct contact challenge with FMD virus from five further non-vaccinated cattle infected 24h earlier with O UKG 34/2001. All vaccinated cattle regardless of antigen payload were protected against clinical disease. Sub-clinical oropharyngeal infection was detected in animals from both experiments but the level of virus replication shortly after direct contact challenge was significantly reduced in vaccinated animals. Cattle immunised with the 10-fold antigen payload cleared the virus more readily and consequently at 28 days post-challenge fewer animals were persistently infected compared to the single strength vaccine. Following a severe challenge, the results from both experiments show that use of

  20. The time-course of protection of the RTS,S vaccine against malaria infections and clinical disease.

    Science.gov (United States)

    Penny, Melissa A; Pemberton-Ross, Peter; Smith, Thomas A

    2015-11-04

    Recent publications have reported follow-up of the RTS,S/AS01 malaria vaccine candidate Phase III trials at 11 African sites for 32 months (or longer). This includes site- and time-specific estimates of incidence and efficacy against clinical disease with four different vaccination schedules. These data allow estimation of the time-course of protection against infection associated with two different ages of vaccination, both with and without a booster dose. Using an ensemble of individual-based stochastic models, each trial cohort in the Phase III trial was simulated assuming many different hypothetical profiles for the vaccine efficacy against infection in time, for both the primary course and boosting dose and including the potential for either exponential or non-exponential decay. The underlying profile of protection was determined by Bayesian fitting of these model predictions to the site- and time-specific incidence of clinical malaria over 32 months (or longer) of follow-up. Using the same stochastic models, projections of clinical efficacy in each of the sites were modelled and compared to available observed trial data. The initial protection of RTS,S immediately following three doses is estimated as providing an efficacy against infection of 65 % (when immunizing infants aged 6-12 weeks old) and 91 % (immunizing children aged 5-17 months old at first vaccination). This protection decays relatively rapidly, with an approximately exponential decay for the 6-12 weeks old cohort (with a half-life of 7.2 months); for the 5-17 months old cohort a biphasic decay with a similar half-life is predicted, with an initial rapid decay followed by a slower decay. The boosting dose was estimated to return protection to an efficacy against infection of 50-55 % for both cohorts. Estimates of clinical efficacy by trial site are consistent with those reported in the trial for all cohorts. The site- and time-specific clinical observations from the RTS,S/AS01 trial data allowed

  1. Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24-26 January 2013.

    Science.gov (United States)

    Girard, Marc P; Tam, John S; Pervikov, Yuri; Katz, Jacqueline M

    2013-08-20

    On January 24-26, 2013, the World Health Organization convened the first integrated meeting on "The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses" to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issues. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  2. The role of active vaccination in cancer immunotherapy: lessons from clinical trials.

    Science.gov (United States)

    Kissick, Haydn T; Sanda, Martin G

    2015-08-01

    In the past few years, a number of different immunotherapeutic strategies have shown impressive results in cancer patients. These successful approaches include blockade of immunosuppressive molecules like PD-1 and CTLA-4, adoptive transfer of patient derived and genetically modified T-cells, and vaccines that stimulate tumor antigen specific T-cells. However, several large vaccine trials recently failed to reach designated primary endpoints. In light of the success of other immunotherapeutic approaches, these negative results raise the questions of why vaccines have not generated a better response, and what the role of active vaccination will be moving forward in cancer immunotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Reasons for non-adherence to vaccination at mother and child care clinics (MCCs) in Lambaréné, Gabon

    NARCIS (Netherlands)

    Schwarz, Norbert G.; Gysels, Marjolein; Pell, Christopher; Gabor, Julian; Schlie, Meike; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G.; Grobusch, Martin P.; Pool, Robert

    2009-01-01

    The aim of this paper is to explore attitudes of mothers towards childhood vaccinations and reasons for non-attendance and non-adherence to mother-child clinics (MCCs). Forty in-depth interviews with mothers of children under 5 years of age revealed positive attitudes towards vaccination that seem

  4. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Science.gov (United States)

    Grimaldi, Gabriel; Teva, Antonio; Porrozzi, Renato; Pinto, Marcelo A; Marchevsky, Renato S; Rocha, Maria Gabrielle L; Dutra, Miriam S; Bruña-Romero, Oscar; Fernandes, Ana-Paula; Gazzinelli, Ricardo T

    2014-06-01

    Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. The remarkable clinical protection induced by A2 in an animal model that is

  5. Clinical and parasitological protection in a Leishmania infantum-macaque model vaccinated with adenovirus and the recombinant A2 antigen.

    Directory of Open Access Journals (Sweden)

    Gabriel Grimaldi

    2014-06-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2 protein that protects against experimental L. infantum infections in mice and dogs. METHODOLOGY/PRINCIPAL FINDINGS: Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12 adsorbed in alum (rA2/rhIL-12/alum; two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2 followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum; and plasmid DNA encoding A2 gene (DNA-A2 boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2. Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. CONCLUSIONS

  6. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

    Science.gov (United States)

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2014-01-01

    Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

  7. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials

    DEFF Research Database (Denmark)

    Petersen, Lone K; Restrepo, Jaime; Moreira, Edson D

    2017-01-01

    BACKGROUND: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody...... responses was assessed. METHODS: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized...... as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. RESULTS: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined...

  8. Clinical course of H1N1-vaccine-related narcolepsy.

    Science.gov (United States)

    Sarkanen, Tomi; Alakuijala, Anniina; Partinen, Markku

    2016-03-01

    To follow and analyze the clinical course and quality of life of Pandemrix H1N1-vaccine-related narcolepsy (pNT1). Twenty-six drug-naïve confirmed pNT1 subjects completed Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), Swiss Narcolepsy Scale (SNS), Rimon's Brief Depression scale (RDS), and WHO-5 Well-being index questionnaires near the disease onset and in a follow-up a minimum of two years later. The number of cataplexies and body mass index (BMI) were recorded. The effects of hypocretin-1 levels and sleep recording results were analyzed. The findings at the follow-up visit were compared with 25 non-vaccine-related type 1 narcolepsy (NT1) subjects. In pNT1, RDS score decreased significantly (mean 10.2, SD 4.7 vs mean 6.7, SD 4.5, p = 0.003). Median of BMI increased from 20.8 kg m(-2) to 23.4 kg m(-2), p <0.001. There were no significant differences in other sleep scores. However, deviation and range in questionnaire scores at the follow-up were wide. Subjects with very low or undetectable hypocretin-1 levels had worse scores in UNS (mean 26.4, SD 6.95 vs mean 19.1, SD 3.83, p = 0.006) and ESS (mean 17.9, SD = 4.29 vs mean 14.1, SD = 3.70, p = 0.047) than those with hypocretin-1 levels of 20-110 pg/mL. Most disabling symptoms were excessive daytime sleepiness and disturbed sleep. There were no significant differences between the scores in pNT1 and NT1. Clinical course of pNT1 is heterogeneous but the evolution of pNT1 seems similar to NT1. Lower hypocretin levels in pNT1 are associated with a more severe phenotype. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. HPV Vaccine Acceptance in a Clinic-Based Sample of Women in the Rural South

    Science.gov (United States)

    Brandt, Heather M.; Sharpe, Patricia A.; McCree, Donna H.; Wright, Marcie S.; Davis, Jennifer; Hutto, Brent E.

    2009-01-01

    Background: Human papillomavirus (HPV) is a very common sexually transmitted infection linked to cervical disease. Vaccines for some types of HPV were in development at the time of the study. Purpose: The study examined HPV vaccine acceptability among underserved women in a rural region of the southeastern U.S. with high rates of cervical cancer…

  10. 76 FR 68768 - Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines; Availability

    Science.gov (United States)

    2011-11-07

    ... applies to therapeutic cancer vaccines that are intended for the treatment of patients with an existing... cancer vaccines that are intended for the treatment of patients with an existing diagnosis of cancer. The... [Federal Register Volume 76, Number 215 (Monday, November 7, 2011)] [Notices] [Pages 68768-68769...

  11. Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized, double-blind, multi-center, phase 3 clinical trial.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Woo, Heung Jeong; Wie, Seong-Heon; Lee, Jin-Soo; Kim, Shin Woo; Noh, Ji Yun; Choi, Won Suk; Kim, Hun; Kim, Kyung-Ho; Kim, Woo Joo

    2015-10-05

    Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity. A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (AgrippalS1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination. A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups. NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. An inactivated gE-deleted pseudorabies vaccine provides complete clinical protection and reduces virus shedding against challenge by a Chinese pseudorabies variant.

    Science.gov (United States)

    Wang, Jichun; Guo, Rongli; Qiao, Yongfeng; Xu, Mengwei; Wang, Zhisheng; Liu, Yamei; Gu, Yiqi; Liu, Chang; Hou, Jibo

    2016-12-07

    Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult. An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-AB) strain. PRV(LA-AB) strain can reach a titer of 108.43 TCID50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-AB) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-AB strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3-4 days) was shorter than in either the challenge control (5-10 days) or groups C and D (5-6 days). The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-AB)strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-AB provides clinical protection

  13. Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination.

    Science.gov (United States)

    Kim, Ahlee; Chang, Ju Young; Shin, Sue; Yi, Hana; Moon, Jin Soo; Ko, Jae Sung; Oh, Sohee

    2017-03-01

    We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.

  14. Identification of potential new protein vaccine candidates through pan-surfomic analysis of pneumococcal clinical isolates from adults.

    Directory of Open Access Journals (Sweden)

    Alfonso Olaya-Abril

    Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.

  15. A two-stage, multilevel quality control system for serological assays in anthrax vaccine clinical trials.

    Science.gov (United States)

    Soroka, Stephen D; Schiffer, Jarad M; Semenova, Vera A; Li, Han; Foster, Lydia; Quinn, Conrad P

    2010-11-01

    A two-stage, multilevel assay quality control (QC) system was designed and implemented for two high stringency QC anthrax serological assays; a quantitative anti-PA IgG enzyme-linked immunosorbent assay (ELISA) and an anthrax lethal toxin neutralization activity (TNA) assay. The QC system and the assays were applied for the congressionally mandated Centers for Disease Control and Prevention (CDC) Phase 4 human clinical trial of anthrax vaccine adsorbed (AVA, BioThrax). A total of 57,284 human serum samples were evaluated by anti-PA enzyme-linked immunosorbent assay (ELISA) and 11,685 samples by anthrax lethal toxin neutralization activity (TNA) assay. The QC system demonstrated overall sample acceptance rates of 86% for ELISA and 90% for the TNA assays respectively. Monitoring of multiple assay and test sample variables showed no significant long term trends or degradation in any of the critical assay reagents or reportable values for both assays. Assay quality control data establish the functionality of the quality control system and demonstrates the reliability of the serological data generated using these assays. Published by Elsevier Ltd.

  16. HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains.

    Science.gov (United States)

    Luytjes, Willem; Enouf, Vincent; Schipper, Maarten; Gijzen, Karlijn; Liu, Wai Ming; van der Lubben, Mariken; Meijer, Adam; van der Werf, Sylvie; Soethout, Ernst C

    2012-07-27

    Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Selection of glutamate-rich protein long synthetic peptides for vaccine development: antigenicity and relationship with clinical protection and immunogenicity

    DEFF Research Database (Denmark)

    Theisen, M; Dodoo, D; Toure-Balde, A

    2001-01-01

    from clinical P. falciparum malaria. Protected children from the Ghana cohort possessed predominantly IgG1 antibodies against the nonrepeat epitope and IgG3 antibodies against the repeat epitope. T-cell proliferation responses, studied in the cohort from Senegal, revealed that T-helper-cell epitopes...... antisera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relatively conserved epitopes of GLURP might serve as useful immunogens for vaccination against P. falciparum malaria....

  18. Association of Escherichia coli J5-Specific Serum Antibody Responses with Clinical Mastitis Outcome for J5 Vaccinate and Control Dairy Cattle ▿

    Science.gov (United States)

    Wilson, David J.; Mallard, Bonnie A.; Burton, Jeanne L.; Schukken, Ynte H.; Grohn, Yrjo T.

    2009-01-01

    Dairy cattle in two commercial Holstein herds were randomly selected to be vaccinated twice with J5, at approximately 60 days and 28 days before the expected calving date, or to be untreated controls. Based on whether milk production changed following clinical mastitis or whether cows were culled or died within 30 days after onset, 51 mastitis cases were classified as severe or mild. J5-specific antibody responses were evaluated by enzyme-linked immunosorbent assay of all 32 severe and 19 mild cases. The amounts of J5-specific immunoglobulin M (IgM), IgG1, and IgG2 antibodies in sera from the 27 J5 vaccinates were compared with those of the 24 controls. At drying off (before J5 vaccination), all cows had similar amounts of J5-specific antibody. Immediately after calving (approximately 28 days after the second vaccination), J5 vaccinates had significantly higher production of J5-specific IgG1 and IgG2 than controls. When cows were tested following clinical mastitis, none of the three antibody classes differed significantly between the controls and the vaccinates. Vaccinates that contracted Escherichia coli mastitis had 75% less milk loss than controls. The cows that contracted clinical mastitis later in lactation, the unvaccinated controls, and those infected with E. coli had more milk loss following mastitis. The hazards of being culled for all reasons and of being culled for mastitis were significantly lower for J5 vaccinates. Vaccination with J5 was associated with protection against milk production loss and culling following clinical mastitis, and it was also significantly associated with changes in J5-specific IgM, IgG1, and IgG2 antibodies in sera of vaccinated cows. PMID:19052158

  19. Association of Escherichia coli J5-specific serum antibody responses with clinical mastitis outcome for J5 vaccinate and control dairy cattle.

    Science.gov (United States)

    Wilson, David J; Mallard, Bonnie A; Burton, Jeanne L; Schukken, Ynte H; Grohn, Yrjo T

    2009-02-01

    Dairy cattle in two commercial Holstein herds were randomly selected to be vaccinated twice with J5, at approximately 60 days and 28 days before the expected calving date, or to be untreated controls. Based on whether milk production changed following clinical mastitis or whether cows were culled or died within 30 days after onset, 51 mastitis cases were classified as severe or mild. J5-specific antibody responses were evaluated by enzyme-linked immunosorbent assay of all 32 severe and 19 mild cases. The amounts of J5-specific immunoglobulin M (IgM), IgG1, and IgG2 antibodies in sera from the 27 J5 vaccinates were compared with those of the 24 controls. At drying off (before J5 vaccination), all cows had similar amounts of J5-specific antibody. Immediately after calving (approximately 28 days after the second vaccination), J5 vaccinates had significantly higher production of J5-specific IgG1 and IgG2 than controls. When cows were tested following clinical mastitis, none of the three antibody classes differed significantly between the controls and the vaccinates. Vaccinates that contracted Escherichia coli mastitis had 75% less milk loss than controls. The cows that contracted clinical mastitis later in lactation, the unvaccinated controls, and those infected with E. coli had more milk loss following mastitis. The hazards of being culled for all reasons and of being culled for mastitis were significantly lower for J5 vaccinates. Vaccination with J5 was associated with protection against milk production loss and culling following clinical mastitis, and it was also significantly associated with changes in J5-specific IgM, IgG1, and IgG2 antibodies in sera of vaccinated cows.

  20. Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines.

    Science.gov (United States)

    Howard, M Keith; Kistner, Otfried; Barrett, P Noel

    2008-05-01

    The rapid spread of avian influenza (H5N1) and its transmission to humans has raised the possibility of an imminent pandemic and concerns over the ability of standard influenza vaccine production methods to supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains, produced at a variety of manufacturing scales, were demonstrated to be highly immunogenic in animal models without the need for adjuvant. The vaccines induce cross-neutralising antibodies and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from other clades. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high-yield production of a candidate pandemic vaccine.

  1. A novel peptide-based pan-influenza A vaccine: a double blind, randomised clinical trial of immunogenicity and safety.

    Science.gov (United States)

    Francis, James N; Bunce, Campbell J; Horlock, Claire; Watson, Jeannette M; Warrington, Steven J; Georges, Bertrand; Brown, Carlton B

    2015-01-03

    FP-01.1 is a novel synthetic influenza A vaccine consisting of six fluorocarbon-modified 35-mer peptides that encapsulate multiple CD4+ and CD8+ T-cell epitopes and is designed to induce an immune response across a broad population. FP-01.1 was evaluated for safety and immunogenicity in a randomised, double-blind, placebo-controlled, dose-escalation, phase I clinical study in healthy adult volunteers (n=49). IFNγ ELISpot assays and multicolour flow cytometry were used to characterise the immune response. FP-01.1 was safe and well tolerated at all doses tested with a similar adverse event profile in actively vaccinated subjects compared with controls. Maximum immunogenicity was in the 150 μg/peptide dose group where a robust response (243 spots/million PBMC) was demonstrated in 75% subjects compared with 0% in placebo controls. All six peptides were immunogenic. FP-01.1 induced dual CD4+ and CD8+ T cell responses and vaccine-specific T cells cross-recognise divergent influenza strains. This first-in-human study showed that FP-01.1 has an acceptable safety and tolerability profile and generated robust anti-viral T cell responses in a high proportion of subjects tested. The results support the further clinical testing of FP-01.1 prior to clinical, proof-of-concept, live viral challenge studies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. 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

    of administration, except varicella-like rashes, which were less frequent in the IM group. Conclusion The immunogenicities of M-M-RvaxPro and VARIVAX administered by the intramuscular route were comparable with those following subcutaneous administration, and the tolerability of the two vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route in routine clinical practice. Trial registration ClinicalTrials.gov NCT00432523

  3. Attitudes towards antenatal vaccination, Group B streptococcus and participation in clinical trials: Insights from focus groups and interviews of parents and healthcare professionals.

    Science.gov (United States)

    McQuaid, Fiona; Pask, Sophie; Locock, Louise; Davis, Elizabeth; Stevens, Zoe; Plumb, Jane; Snape, Matthew D

    2016-07-25

    Antenatal vaccination has become a part of routine care during pregnancy in the UK and worldwide, leading to improvements in health for both pregnant women and their infants. However, uptake remains sub-optimal. Other antenatal vaccines targeting major neonatal pathogens, such as Group B streptococcus (GBS), the commonest cause of sepsis and meningitis in the neonatal period, are undergoing clinical trials but more information is needed on how to improve acceptance of such vaccines. Qualitative study using focus groups and interviews; involving 14 pregnant women, 8 mothers with experience of GBS, and 28 maternity healthcare professionals. Questions were asked regarding antenatal vaccines, knowledge of GBS, attitudes to a potential future GBS vaccine and participation in antenatal vaccine trials. All participants were very cautious about vaccination during pregnancy, with harm to the baby being a major concern. Despite this, the pregnant women and parents with experience of GBS were open to the idea of an antenatal GBS vaccine and participating in research, while the maternity professionals were less positive. Major barriers identified included lack of knowledge about GBS and the reluctance of maternity professionals to be involved. In order for a future GBS vaccine to be acceptable to both pregnant women and the healthcare professionals advising them, a major awareness campaign would be required with significant focus on convincing and training maternity professionals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

    Science.gov (United States)

    Woestenberg, Petra J; King, Audrey J; van Benthem, Birgit H B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; de Melker, Hester E; van der Sande, Marianne A B; Hoebe, Christian J P A; Bogaards, Johannes A

    2018-01-04

    Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

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

    Science.gov (United States)

    van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

    2011-01-01

    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. 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. 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. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

  6. Efficacy of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical, virological, pathological and immunological examination under field conditions.

    Science.gov (United States)

    Seo, Hwi Won; Han, Kiwon; Oh, Yeonsu; Park, Changhoon; Chae, Chanhee

    2012-10-19

    Inactivated chimeric porcine circovirus (PCV) 1-2 vaccine was initially taken off the market due to concerns that the vaccine virus was not killed and thus further replicated and spread in the pig population. In August 2011, a reformulated inactivated chimeric PCV1-2 vaccine re-entered the market. The efficacy of the reformulated inactivated chimeric PCV1-2 vaccine was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of postweaning multisystemic wasting syndrome (PMWS). On each farm, a total of 50 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated at 3 weeks of age and (ii) non-vaccinated. Clinical examination indicated that vaccinated animals displayed an improved average daily weight gain (672.2g/day vs. 625g/day; difference of +47.3g/day; Pantibodies (NA) and interferon-γ-secreting cells (IFN-γ-SCs). A reduction in the PCV2 load in the blood coincided with the appearance of both PCV2-specific NA and IFN-γ-SCs in the vaccinated animals. The number of CD4(+) cells was decreased in non-vaccinated animals compared to vaccinated animals. The reformulated inactivated chimeric PCV1-2 vaccine seems to be very effective in controlling PCV2 infection based on clinical, virological, pathological, and immunological evaluations under field conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. 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 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.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.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.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

  8. Clinical and economic impact of school-based nonavalent human papillomavirus vaccine on women in Singapore: a transmission dynamic mathematical model analysis.

    Science.gov (United States)

    Tay, S K; Hsu, T-Y; Pavelyev, A; Walia, A; Kulkarni, A S

    2018-03-01

    To examine the epidemiological and economic impact of a nine-valent (nonavalent) human papillomavirus (HPV) 6/11/16/18/31/33/45/52/58 vaccine programme for young teenagers in Singapore. Mathematical modelling. Pharmaco-economic simulation projection. Singapore demography. Clinical, epidemiological and financial data from Singapore were used in a validated HPV transmission dynamic mathematical model to analyse the impact of nonavalent HPV vaccination over quadrivalent and bivalent vaccines in a school-based 2-dose vaccination for 11- to 12-year-old girls in the country. The model assumed routine cytology screening in the current rate (50%) and vaccine coverage rate of 80%. Changes over a 100-year time period in the incidence and mortality rates of cervical cancer, case load of genital warts, and incremental cost-effectiveness ratio (ICER). Compared with bivalent and quadrivalent HPV vaccination programmes, nonavalent HPV universal vaccination resulted in an additional reduction of HPV31/33/45/52/58 related CIN1 of 40.5%, CIN 2/3 of 35.4%, cervical cancer of 23.5%, and cervical cancer mortality of 20.2%. Compared with bivalent HPV vaccination, there was an additional reduction in HPV-6/11 related CIN1 of 75.7%, and genital warts of 78.9% in women and 73.4% in men. Over the 100 years, after applying a discount of 3%, disease management cost will be reduced by 32.5% (versus bivalent) and 7.5% (versus quadrivalent). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year gained was SGD 929 compared with bivalent vaccination and SGD 9864 compared with quadrivalent vaccination. Universal two-dose nonavalent HPV vaccination for 11- to 12-year-old adolescent women is very cost-effective in Singapore. Nonavalent HPV vaccination of 11- to 12-year-old girls is cost-effective in Singapore. © 2017 Royal College of Obstetricians and Gynaecologists.

  9. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine – A combined analysis of five phase III clinical trials

    Directory of Open Access Journals (Sweden)

    Lone K. Petersen

    2017-06-01

    Full Text Available Background: The immunogenicity profile of the 9-valent HPV (9vHPV vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9–15 years of age and young women 16–26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody responses was assessed. Methods: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized as geometric mean titers (GMTs. Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. Results: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1. Conclusions: 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination. Studies in the meta-analysis: V503-001, V503-002, V503-005, V503-007, V503-009/GDS01C, Clinical trials

  10. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial

    DEFF Research Database (Denmark)

    Martins, C.L.; Garly, May-Lill; Bale, C.

    2008-01-01

    Objective To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age. Design Randomised clinical trial. Participants 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group. Setting Urban area in Guinea-Bissau. Interve......Objective To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age. Design Randomised clinical trial. Participants 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group. Setting Urban area in Guinea......-Bissau. Intervention Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age. Main outcome measures Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age. Results 28% of the children tested at 4.......5 months of age had protective levels of maternal antibodies against measles at enrolment. After early vaccination against measles 92% had measles antibodies at 9 months of age. A measles outbreak offered a unique situation for testing the efficacy of early measles vaccination. During the outbreak, 96...

  11. BCG Vaccines.

    Science.gov (United States)

    Tran, Vanessa; Liu, Jun; Behr, Marcel A

    2014-02-01

    BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.

  12. Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

    Science.gov (United States)

    Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

    2016-05-01

    This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. The Recombinant Bacille Calmette–Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing

    National Research Council Canada - National Science Library

    Natalie E. Nieuwenhuizen; Prasad S. Kulkarni; Umesh Shaligram; Mark F. Cotton; Cyrill A. Rentsch; Bernd Eisele; Leander Grode; Stefan H. E. Kaufmann

    2017-01-01

    The only licensed vaccine against tuberculosis (TB), bacille Calmette–Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB...

  14. DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies

    National Research Council Canada - National Science Library

    Han, Kyusun Torque; Sin, Jeong-Im

    2013-01-01

    .... Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated cancers...

  15. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    OpenAIRE

    Mold, M; Shardlow, E; Exley, C

    2016-01-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, pote...

  16. The uptake of influenza and pneumococcal vaccination among immunocompromised patients attending rheumatology outpatient clinics.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-07-01

    PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.

  17. Burkholderia pseudomallei and Burkholderia mallei vaccines: Are we close to clinical trials?

    Science.gov (United States)

    Titball, Richard W; Burtnick, Mary N; Bancroft, Gregory J; Brett, Paul

    2017-10-20

    B. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. The closely related bacterium B. mallei, which cases glanders, is considered to be a clonal derivative of B. pseudomallei. Both B. pseudomallei and B. mallei were evaluated by the United States and the former USSR as potential bioweapons. Much of the effort to devise biodefence vaccines in the past decade has been directed towards the identification and formulation of sub-unit vaccines which could protect against both melioidosis and glanders. A wide range of proteins and polysaccharides have been identified which protective immunity in mice. In this review we highlight the significant progress that has been made in developing glycoconjugates as sub-unit vaccines. We also consider some of the important the criteria for licensing, including the suitability of the "animal rule" for assessing vaccine efficacy, the protection required from a vaccine and the how correlates of protection will be identified. Vaccines developed for biodefence purposes could also be used in regions of the world where naturally occurring disease is endemic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Toh, Han Chong; Wang, Who-Whong; Chia, Whay Kuang

    2009-01-01

    PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs...... late tumor regression, yielding a clinical benefit response rate of 40% (95% CI, 22-61%). Although overall median progression-free survival was 2.4 months (95% CI, 1.9-4.1 months), five patients (25%) experienced prolonged progression-free survival (>6 months), two of whom (10%) remain progression...

  19. Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

    Science.gov (United States)

    Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A

    2014-01-01

    The human, G1P[8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. PMID:22520123

  20. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    Science.gov (United States)

    Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-04-01

    To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

  1. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  2. Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

    Science.gov (United States)

    Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

    2014-05-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

  3. The optimal number of routine vaccines to order at health clinics in low or middle income countries.

    Science.gov (United States)

    Rajgopal, Jayant; Connor, Diana L; Assi, Tina-Marie; Norman, Bryan A; Chen, Sheng-I; Bailey, Rachel R; Long, Adrienne R; Wateska, Angela R; Bacon, Kristina M; Brown, Shawn T; Burke, Donald S; Lee, Bruce Y

    2011-07-26

    In a low or middle income country, determining the correct number of routine vaccines to order at a health clinic can be difficult, especially given the variability in the number of patients arriving, minimal vaccination days and resource (e.g., information technology and refrigerator space) constraints. We developed a spreadsheet model to determine the potential impact of different ordering policies, basing orders on the arrival rates seen in the previous 1, 3, 6, or 12 sessions, or on long-term historical averages (where these might be available) along with various buffer stock levels (range: 5-50%). Experiments varied patient arrival rates (mean range: 1-30 per session), arrival rate distributions (Poisson, Normal, and Uniform) and vaccine vial sizes (range: 1-dose to 10-dose vials). It was found that when the number of doses per vial is small and the expected number of patients is low, the ordering policy has a more significant impact on the ability to meet demand. Using data from more prior sessions to determine arrival rates generally equates to a better ability to meet demand, although the marginal benefit is relatively small after more than 6 sessions are averaged. As expected, the addition of more buffer is helpful in obtaining better performance; however, this advantage also has notable diminishing returns. In general, the long-term demand rate, the vial sizes of the vaccines used and the method of determining the patient arrival rate all have an effect on the ability of a clinic to maximize the demand that is met. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. [Development of anti-malarial vaccines and need for clinical trials in accordance with international standards in South Africa].

    Science.gov (United States)

    Doumbo, O K; Djimdé, A A; Théra, M A

    2008-06-01

    In the 20th century malaria remains a major problem of public health in sub-Saharan Africa. This haemosporidium discovered in Africa by Laveran in 1880, kills one child every 30 seconds which amounts to three "tsunami" flowing each year into the African continent. The current international solidarity raises new hopes as regards the possibility to suppress the morbidity effects on the population's health condition. In order to be efficient, today's strategies (impregnated mosquito nets, intermittent preventive treatments, artemisinin based combination therapy) should reach at least 80% of the targeted population (pregnant women and children). By 2025, the uncontrolled urbanization of the African population and the social disorders will make a new population a target for malaria. The new data of functional genomics and proteonics open new avenues of research for new mechanisms, new therapeutics and vaccine targets and new tools of diagnosis and prognosis. The current candidate vaccines of the first generation have allowed the development of African competences in clinical trials of international standard. Although they represent scientific advances they will not resolve the problem of public health. Research on candidate vaccines of 2nd and 3rd generation remains a challenge for the international scientific community. Africa should play a determining role in this process. Scientific information on the field remains essential for these generations of new anti-malarial vaccines. The ethical aspects regarding those clinical trials and actions of public health and research remain an universal necessity Deontology and ethics are two complementary approaches for the good practice of medicine and research of a good practitioner. For the protection and advantages of the patient and/or volunteer of the research are the cornerstones of the ethical approach. The scientific quality of a research protocol submitted to an independent research ethics committee and the volunteer 's

  5. Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis.

    Science.gov (United States)

    Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, José M; Fichera, Epifanio; Reed, Steven G; Coler, Rhea N; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav; Cordeiro-da-Silva, Anabela

    2017-11-01

    The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".

  6. 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 ...

  7. Design and pre-clinical evaluation of a universal HIV-1 vaccine.

    Directory of Open Access Journals (Sweden)

    Sven Létourneau

    2007-10-01

    Full Text Available One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV, by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA, and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+ and CD4(+ T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.

  8. Clinical and epidemiological characteristics of severe community-acquired pneumonia in children after introduction of the 10-valent pneumococcal vaccine

    Directory of Open Access Journals (Sweden)

    Lima EJF

    2015-08-01

    Full Text Available Eduardo JF Lima,1,2 Maria JG Mello,1,2 Maria FPM Albuquerque,3 Maria IL Lopes,4 George HC Serra,2 Maria AZ Abreu-Lima,2 Jailson B Correia1 1Instituto de Medicina Integral Prof. Fernando Figueira - IMIP Recife; 2Faculdade, Pernambucana de Saúde - FPS Recife; 3Centro de Pesquisas Aggeu Magalhães, FIOCRUZ; 4Hospital das Clínicas, Universidade Federal de Pernambuco - UFPE, Recife, Pernambuco, Brazil Background: Pneumonia is an important cause of morbimortality in Brazil, despite the extensive vaccination coverage and the socioeconomic improvement in the past years. Objective: To describe the epidemiological and clinical characteristics of severe community-acquired pneumonia in children after the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10. Methods: A prospective study included children <5 years old hospitalized for pneumonia between October 2010 and September 2013 in a tertiary hospital. Newborns and children with comorbidities were excluded. Pneumonia classification followed the clinical and radiological criteria established by World Health Organization (WHO. Clinical history, nutritional status, immunizations, diagnosis, disease course, and prognosis were analyzed. Results: Among 452 children, almost 70% were <2 years, with no sex differences, and 10% had weight-for-age z score below than -2.0. Family income was up to one minimum wage in half the households, and 40% of mothers had completed high school. The suitability of both influenza and PCV10 vaccine schedules was ~50%. The first medical care happened later than 72 hours after the onset of symptoms in 42% of cases. Pneumonia was classified as severe or very severe in 83.9% of patients and for 23% as complicated. Global mortality was 1.5%. Hypoxia, diagnosed in 51.5% of children, looked like a better prognosis predictor than the WHO classification. Conclusion: New strategies for health care are necessary, such as the incorporation of peripheral saturometry as the

  9. Economic Cost of Ovine Johne’s Disease in Clinically Affected New Zealand Flocks and Benefit-Cost of Vaccination

    Directory of Open Access Journals (Sweden)

    Milan Gautam

    2018-01-01

    Full Text Available The aims of this study were to estimate the on-fam economic cost of ovine Johne’s disease (OJD based on collected incidence and mortality data, and the benefit-cost of OJD vaccination in typical OJD affected flocks in New Zealand after having vaccinated for a number of years. Owners of 20 sheep breeding and finishing farms known to be clinically affected by ovine Johne’s disease in New Zealand participated in the study and were monitored for up to two years. Farms were categorized as fine-wool (Merino, Half-Bred, Corriedale, n = 15, and other breeds (Romney, composite breeds, n = 5. Ovine JD was confirmed by gross- and histo-pathology in 358 ewes culled due to chronic progressive wasting. An additional 228 ewes with low body condition score (BCS, but not targeted for culling, were tested with ELISA to estimate the proportion of OJD in ewes in the lower 5% BCS of the flock. Calculations were done separately for fine-wool and other breeds. Based on the data, mortality due to OJD, its associated cost and the benefit-cost of vaccination were evaluated for a hypothetical farm with 2000 ewes by stochastic simulation. Total ewe mortality was similar in fine-wool and other breeds, but the estimated mortality due to OJD was 2.7 times as high in fine-wool (median 1.8%, interquartile range IQR 1.2–2.7% than other breeds (median 0.69%, IQR 0.3–1.2%, but with large variation between farms. ELISA results demonstrated fine-wool sheep had a higher seroprevalence than other breeds (39%, 95% CI 18–61% vs. 9%, 95% CI 0–22%. Stochastic modelling indicated that the average annual cost of mortality due to OJD in a flock of 2000 ewes was NZD 13,100 (IQR 8900–18,600 in fine-wool and NZD 4300 (IQR 2200–7600 in other breeds. Vaccinating replacement lambs against OJD may be cost-effective in most flocks when the pre-vaccination annual ewe mortality due to OJD is >1%. To make the best-informed decision about vaccination it is therefore essential for farmers

  10. ISCOM-based equine influenza vaccine: Duration of immunity and randomised clinical trials to assess an accelerated schedule of immunisation and efficacy

    Directory of Open Access Journals (Sweden)

    R. Paillot

    2015-01-01

    Study 3: efficacy against Florida clade 2 EIV strain (randomised trial. Efficacy against the representative Florida clade 2 strain A/eq/Richmond/1/07 was also evaluated at the peak of immunity, shortly after 2nd vaccination (V2. Six ponies were vaccinated with EquipFT according to label (6-week interval between first and second injection and 6 control ponies received saline injections. Sixteen days after V2 (day 58, all animals were experimentally infected with A/eq/Richmond/1/07. Clinical signs of disease and virus shedding were assessed for 14 days and found to be significantly reduced in vaccinated animals.

  11. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S

    2008-01-01

    Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer...

  12. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine

    DEFF Research Database (Denmark)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-01-01

    Introduction: Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which...... are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered...

  13. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  14. Phase I randomised clinical trial of an HIV-1(CN54, clade C, trimeric envelope vaccine candidate delivered vaginally.

    Directory of Open Access Journals (Sweden)

    David J Lewis

    Full Text Available We conducted a phase 1 double-blind randomised controlled trial (RCT of a HIV-1 envelope protein (CN54 gp140 candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18-45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women.ClinicalTrials.gov NCT00637962.

  15. Clinical Severity and Rotavirus Vaccination among Children Hospitalized for Acute Gastroenteritis in Belém, Northern Brazil.

    Science.gov (United States)

    Justino, Maria Cleonice A; Brasil, Patrícia; Abreu, Erika; Miranda, Yllen; Mascarenhas, Joana D'Arc P; Guerra, Sylvia F S; Linhares, Alexandre C

    2016-08-01

    In March 2006, Brazil introduced the monovalent rotavirus (RV) vaccine (Rotarix™) into the public sector. This study assessed the severity of rotavirus gastroenteritis (RVGE) according to the vaccination status among hospitalized children. We identified 1023 RVGE episodes among not vaccinated (n = 252), partially vaccinated (n = 156) and fully vaccinated (n = 615) children. Very severe gastroenteritis (scored ≥ 15) was reported in 16.7, 17.9 and 13.5% of not vaccinated, partially vaccinated and fully vaccinated children, respectively. There was a trend for a shorter duration of RV diarrhoea among vaccinated children than in not vaccinated children (p = 0.07). A protective effect of vaccination was noted when mean duration of symptoms and hospital stay are analysed, comparing unvaccinated, partially vaccinated and fully vaccinated children (p vaccination dose effect trend, with fully vaccinated children having less-severe RVGE than not vaccinated and partially vaccinated children. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Xenogeneic therapeutic cancer vaccines as breakers of immune tolerance for clinical application: to use or not to use?

    Science.gov (United States)

    Strioga, Marius M; Darinskas, Adas; Pasukoniene, Vita; Mlynska, Agata; Ostapenko, Valerijus; Schijns, Virgil

    2014-07-07

    Accumulation of firm evidence that clinically apparent cancer develops only when malignant cells manage to escape immunosurveillance led to the introduction of tumor immunotherapy strategies aiming to reprogramm the cancer-dysbalanced antitumor immunity and restore its capacity to control tumor growth. There are several immunotherapeutical strategies, among which specific active immunotherapy or therapeutic cancer vaccination is one of the most promising. It targets dendritic cells (DCs) which have a unique ability of inducing naive and central memory T cell-mediated immune response in the most efficient manner. DCs can be therapeutically targeted either in vivo/in situ or by ex vivo manipulations followed by their re-injection back into the same patient. The majority of current DC targeting strategies are based on autologous or allogeneic tumor-associated antigens (TAAs) which possess various degrees of inherent tolerogenic potential. Therefore still limited efficacy of various tumor immunotherapy approaches may be attributed, among various other mechanisms, to the insufficient immunogenicity of self-protein-derived TAAs. Based on such an idea, the use of homologous xenogeneic antigens, derived from different species was suggested to overcome the natural immune tolerance to self TAAs. Xenoantigens are supposed to differ sufficiently from self antigens to a degree that renders them immunogenic, but at the same time preserves an optimal homology range with self proteins still allowing xenoantigens to induce cross-reactive T cells. Here we discuss the concept of xenogeneic vaccination, describe the cons and pros of autologous/allogeneic versus xenogeneic therapeutic cancer vaccines, present the results of various pre-clinical and several clinical studies and highlight the future perspectives of integrating xenovaccination into rapidly developing tumor immunotherapy regimens. Copyright © 2014. Published by Elsevier Ltd.

  17. Health education through analogies: preparation of a community for clinical trials of a vaccine against hookworm in an endemic area of Brazil.

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    Maria Flavia Gazzinelli

    Full Text Available BACKGROUND: Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research. METHODOLOGY/PRINCIPAL FINDINGS: An informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials. The questionnaire was administered before being shown the educational video and two months after and the results compared. After viewing the video, significant improvements in knowledge related to hookworm infection and its health impact were observed: using a composite score combining related questions for which correct answers were assigned a value of 1 and incorrect answers a value of 0, participants had a mean score of 0.76 post-video compared to 0.68 pre-video (p = 0.0001. Similar improvements were seen in understanding the purpose of vaccination and the possible adverse effects of an experimental vaccine. Although 100% of participants expressed a positive opinion of the researchers even before viewing the film and over 90% said that they would participate in a hookworm vaccine

  18. Health education through analogies: preparation of a community for clinical trials of a vaccine against hookworm in an endemic area of Brazil.

    Science.gov (United States)

    Gazzinelli, Maria Flavia; Lobato, Lucas; Matoso, Leonardo; Avila, Renato; de Cassia Marques, Rita; Shah Brown, Ami; Correa-Oliveira, Rodrigo; Bethony, Jeffrey M; Diemert, David J

    2010-07-20

    Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research. An informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials. The questionnaire was administered before being shown the educational video and two months after and the results compared. After viewing the video, significant improvements in knowledge related to hookworm infection and its health impact were observed: using a composite score combining related questions for which correct answers were assigned a value of 1 and incorrect answers a value of 0, participants had a mean score of 0.76 post-video compared to 0.68 pre-video (p = 0.0001). Similar improvements were seen in understanding the purpose of vaccination and the possible adverse effects of an experimental vaccine. Although 100% of participants expressed a positive opinion of the researchers even before viewing the film and over 90% said that they would participate in a hookworm vaccine trial, an increase in the number who expressed fear of being

  19. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

    Science.gov (United States)

    Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

    2013-10-25

    Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. CLINICAL STUDIES OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF LIVE MONOVALENT INFLUENZA VACCINE (STRAIN А/17/CALIFORNIA/2009/38 — H1N1 IN CHILDREN

    Directory of Open Access Journals (Sweden)

    D.S. Bushmenkov

    2010-01-01

    Full Text Available Results of performed pre-clinical and clinical studies with volunteers 18-60 years old allowed registration of vaccine «INFLUVIR» (live monovalent vaccine for the prophylaxis of influenza A/H1N1, strain A/17/California/2009/38 (H1N1, developed by NPO «Microgen» in Russian Federation so timely vaccination campaign was performed. As a result, the level of morbidity with influenza A/H1N1 in Russia was decreased, and development of complication was prevented. Clinical studies in different groups of children were performed for the purpose of widening indications for vaccine «INFLUVIR» administration. According to the results of studies vaccine «INFLUVIR» has good tolerability and safety, low reactogenicity, and significant immunogenicity. This fact will allow changing of present normative documentation and administration of «INFLUVIR» in children of different age for prophylaxis of influenza A/H1N1.Key words: children, influenza, virus A/H1N1, live influenza vaccine, tolerability, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:101-105

  1. How useful is a history of rubella vaccination for determination of disease susceptibility? A cross-sectional study at a public funded health clinic in Malaysia

    Science.gov (United States)

    2013-01-01

    Background Identification of pregnant women susceptible to rubella is important as vaccination can be given postpartum to prevent future risks of congenital rubella syndrome. However, in Malaysia, rubella antibody screening is not offered routinely to pregnant women in public funded health clinics due to cost constraint. Instead, a history of rubella vaccination is asked to be provided to establish the women’s risk for rubella infection. The usefulness of this history, however, is not established. Thus, this paper aimed to determine the usefulness of a history of rubella vaccination in determining rubella susceptibility in pregnant women. Methods A cross-sectional study was conducted on 500 pregnant women attending a public funded health clinic. Face-to-face interviews were conducted, and demographic data and history of rubella vaccination were obtained. Anti-rubella IgG test was performed. Results A majority of the women (66.6%) had a positive vaccination history. Of these, 92.2% women were immune. A third (33.4%) of the women had a negative or unknown vaccination history, but 81.4% of them were immune to rubella. The sensitivity and specificity of a history of rubella vaccination in identifying disease susceptibility was 54.4% (95% CI: 40.7, 67.4%) and 69.3% (95% CI: 64.7, 73.5%) respectively; the positive predictive value was 18.6% (95% CI: 13.1, 25.5%) and the negative predictive value was 92.2% (95% CI: 88.6, 94.7%). Conclusions A vaccination history of rubella had a poor diagnostic value in predicting rubella susceptibility. However, obtaining a vaccination history is inexpensive compared with performing a serological test. A cost-utility analysis would be useful in determining which test (history versus serological test) is more cost-effective in a country with resource constraint. PMID:23368977

  2. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

    DEFF Research Database (Denmark)

    Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine

    2017-01-01

    Background  The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC...

  3. Adjuvanted versus nonadjuvanted influenza vaccines in young children: comparing results from recent clinical trials

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

    2013-01-01

    textabstractA relatively high burden of influenza is experienced by young children. In order to successfully tackle the burden of influenza in children, effective vaccines are necessary. Accumulated evidence on the efficacy and effectiveness of traditional inactivated split or subunit trivalent

  4. Clinical manifestations of leprosy after BCG vaccination: An observational study in Bangladesh

    NARCIS (Netherlands)

    R. Richardus (Renate); C.R. Butlin (C. Ruth); K. Alam (Khorshed); K. Kundu (Kallyan); A. Geluk (Annemieke); J.H. Richardus (Jan Hendrik)

    2015-01-01

    textabstractBackground: Although BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy,

  5. Vaccination: problems and perspectives.

    Directory of Open Access Journals (Sweden)

    S. M. Kharit

    2009-01-01

    Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

  6. Genetic material should be routinely collected in clinical vaccine trials--high consent rates can be achieved across all age groups.

    Science.gov (United States)

    Trück, Johannes; O'Connor, Daniel; Darton, Tom C; John, Tessa M; Snape, Matthew D; Pollard, Andrew J

    2013-06-07

    Genomic and transcriptomic studies underpin much investigation in biology and should be included routinely in clinical trials such as vaccine studies to provide new insight into the development of immunity and the genetic basis for adverse reactions. Interest in collecting and storing genetic material for subsequent high-throughput meta-analyses has increased substantially in recent years. Participants in clinical trials represent an important and invaluable source of clinical material and data. Here, the experience of a single center in obtaining informed consent for the collection and long-term storage of genetic material from children, adolescents and adults, involved in clinical vaccine trials is presented and discussed. In 11 completed vaccine studies involving almost 3000 individuals, high rates of consent (in excess of 96%) for biobanking and future genetic testing were obtained. Rates were high for participants from all age groups; however, there was a significant increase toward greater uptake by older study participants. These high acceptance rates demonstrate that participants (and parents of young children) in vaccine studies are willing to consent and engage in genetic research, which provides support for routinely collecting genetic material in research involving healthy participants such as clinical vaccine trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

    Directory of Open Access Journals (Sweden)

    Freihorst Joachim

    2007-08-01

    Full Text Available Abstract Background Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial. Methods N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6 or a nasal booster vaccination (n = 6. Antibodies were assessed in induced sputum (IS, bronchoalveolar lavage (BAL, and in serum. Results OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes. Conclusion The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.

  8. [Is it ethically acceptable to invite a pregnant woman to enroll in a clinical trial with Tdap if it could entail not being vaccinated with Tdap before delivery?

    Science.gov (United States)

    Dal-Ré, Rafael

    2017-02-01

    Pertussis incidence has increased in recent years, especially among infants aged <2months. A number of Spanish regions have started a vaccination program with Tdap vaccine to all pregnant women in the third trimester of pregnancy. An observational study has shown that this strategy reduces the number of cases of pertussis by 90% in infants aged <2months. Mathematical models showed that a cocooning strategy (i.e. vaccination of the mother at immediate postpartum, and other adults and adolescents who have close contact with the newborn and caregivers) will reduce the incidence of pertussis by 70% in infants aged <2months. It is intended to conduct a clinical trial in which 340 pregnant women will receive Tdap vaccine, whereas another 340 pregnant woman will be vaccinated soon after delivery. Vaccination with Tdap will be offered to all partners and caregivers of the newborn. After assessing both the ethical and scientific reasons supporting the trial, it is concluded that it is ethically and legally acceptable to invite pregnant women living in communities where Tdap vaccination has been implemented to participate in the trial. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.

    Science.gov (United States)

    Nishiyama, Yasumasa; Fujii, Tatsuya; Kanatani, Yasuhiro; Shinmura, Yasuhiko; Yokote, Hiroyuki; Hashizume, So

    2015-11-09

    In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002. To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees. 268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated. Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination. The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the

  10. A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants.

    Directory of Open Access Journals (Sweden)

    Muhammed O Afolabi

    Full Text Available A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1 during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.From March to October 2010, 48 infants (24 vaccine and 24 no-treatment were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9% and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and

  11. Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A randomised clinical trial

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

    2018-01-01

    Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... age BCG group and 495/1,952 (25.4%) children...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...

  12. Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A randomised clinical trial

    DEFF Research Database (Denmark)

    Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

    2017-01-01

    Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...

  13. Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Danièle Godelaine

    2011-07-01

    Full Text Available Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies.

  14. "PRESUMED SYSTEMIC BACILLE CALMETTE-GUÉRIN DISEASE AFTER BCG VACCINATION: REPORT OF A CLINICAL CASE "

    Directory of Open Access Journals (Sweden)

    P. Tabatabaie

    2006-08-01

    Full Text Available BCG (bacille Calmette–Guérin vaccine is administered worldwide to prevent severe forms of tuberculosis. It is considered to be safe; however, occasional complications are seen. The most serious complication is BCGosis. We report a case of BCGosis with granulomatous hepatitis and acid-fast bacilli in liver and spleen. We treated the patient with antituberculosis drugs without any response to treatment.

  15. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub

  16. Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2007-09-01

    Full Text Available Abstract Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC, there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC, we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF is given continuously (at a rate of 50 μg/24 h at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH skin

  17. Therapeutic vaccination with TNF-Kinoid in TNF antagonist-resistant rheumatoid arthritis: a phase II randomized, controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Patrick Durez

    Full Text Available OBJECTIVES: Active immunization, or vaccination, with tumor necrosis factor (TNF-Kinoid (TNF-K is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA. METHODS: This was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10 or 90 (n = 6, 180 (n = 12, or 360 µg TNF-K (n = 12. The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection. RESULTS: The highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3% and 3 treated with placebo (30.0%, all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not. CONCLUSIONS: TNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent

  18. Intradermal vaccination for infants and children

    OpenAIRE

    Saitoh, Akihiko; Aizawa, Yuta

    2016-01-01

    Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccin...

  19. Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: a randomized clinical trial.

    Science.gov (United States)

    Rongsen-Chandola, Temsunaro; Winje, Brita Askeland; Goyal, Nidhi; Rathore, Sudeep Singh; Mahesh, Madhu; Ranjan, Rajat; Arya, Alok; Rafiqi, Farhana Afzal; Bhandari, Nita; Strand, Tor A

    2014-06-28

    Neutralizing antibodies in breast milk may adversely influence the immune response to live oral vaccines. Withholding breastfeeding around the time of vaccine administration has been suggested for improving vaccine performance. However, we do not know whether mothers find withholding breastfeeding around the time of vaccination acceptable and how they perceive this recommendation. In a clinical study designed to examine predictors of poor immune response to rotavirus vaccine in infants in India, Rotarix® was administered to infants at 6 and 10 weeks with other childhood vaccines. For the study, 400 mother-infant pairs were randomized into two groups in a 1:1 ratio. Mothers were either recommended to withhold breastfeeding or were encouraged to breastfeed half an hour before and after administration of Rotarix®. The mother-infant pairs were observed and the breastfeeding intervals were recorded during this period. Mothers were administered a questionnaire about their perception of the intervention after the infants received the second dose of Rotarix®. Almost 98% (391/400) of the infants received both doses of Rotarix®. Adherence to the recommendations was high in both groups. All mothers in the group who were asked to withhold breastfeeding did so, except one who breastfed her infant before the recommended time after the first dose of Rotarix®. Of the mothers, 4% (7/195) reported that the recommendation to withhold breastfeeding was difficult to follow. All mothers in this group reported that they would withhold breastfeeding at the time of vaccination if they were asked to by a health-care provider. Only one mother responded that withholding breastfeeding would be a reason for not giving rotavirus vaccine to her infant. Withholding breastfeeding half an hour before and after vaccination appears to be acceptable to mothers in this setting. If withholding breastfeeding produces an improvement in the performance of the vaccine, it could be used to increase the

  20. Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing

    Directory of Open Access Journals (Sweden)

    Bappaditya Dey

    2013-01-01

    Full Text Available Part I. Basic Principles. TB vaccines cannot prevent establishment of the infection. They can only prevent an early pulmonary tubercle from developing into clinical disease. A more effective new vaccine should optimize both cell-mediated immunity (CMI and delayed-type hypersensitivity (DTH better than any existing vaccine. The rabbit is the only laboratory animal in which all aspects of the human disease can be reproduced: namely, the prevention of most primary tubercles, the arrestment of most primary tubercles, the formation of the tubercle’s solid caseous center, the liquefaction of this center, the formation of cavities and the bronchial spread of the disease. In liquefied caseum, virulent tubercle bacilli can multiply extracellularly, especially in the liquefied caseum next to the inner wall of a cavity where oxygen is plentiful. The bacilli in liquefied caseum cannot be reached by the increased number of activated macrophages produced by TB vaccines. Therefore, new TB vaccines will have little or no effect on the extracellular bacillary growth within liquefied caseum. TB vaccines can only increase the host’s ability to stop the development of new TB lesions that arise from the bronchial spread of tubercle bacilli from the cavity to other parts of the lung. Therefore, effective TB vaccines do not prevent the reactivation of latent TB. Such vaccines only control (or reduce the number of metastatic lesions that result after the primary TB lesion was reactivated by the liquefaction process. (Note: the large number of tubercle bacilli growing extracellularly in liquefied caseum gives rise to mutations that enable antimicrobial resistance—which is a major reason why TB still exists today. Part II. Preclinical Testing. The counting of grossly visible tubercles in the lungs of rabbits after the inhalation of virulent human-type tubercle bacilli is the most pertinent preclinical method to assess the efficacy of new TB vaccines (because an

  1. Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

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    Apoorva Shankar

    2017-09-01

    Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

  2. Predicting RTS,S Vaccine-Mediated Protection from Transcriptomes in a Malaria-Challenge Clinical Trial

    Directory of Open Access Journals (Sweden)

    Robert A. van den Berg

    2017-05-01

    Full Text Available The RTS,S candidate malaria vaccine can protect against controlled human malaria infection (CHMI, but how protection is achieved remains unclear. Here, we have analyzed longitudinal peripheral blood transcriptome and immunogenicity data from a clinical efficacy trial in which healthy adults received three RTS,S doses 4 weeks apart followed by CHMI 2 weeks later. Multiway partial least squares discriminant analysis (N-PLS-DA of transcriptome data identified 110 genes that could be used in predictive models of protection. Among the 110 genes, 42 had known immune-related functions, including 29 that were related to the NF-κB-signaling pathway and 14 to the IFN-γ-signaling pathway. Post-dose 3 serum IFN-γ concentrations were also correlated with protection; and N-PLS-DA of IFN-γ-signaling pathway transcriptome data selected almost all (44/45 of the representative genes for predictive models of protection. Hence, the identification of the NF-κB and IFN-γ pathways provides further insight into how vaccine-mediated protection may be achieved.

  3. Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

    Science.gov (United States)

    Shankar, Apoorva; Patil, Amulya A.; Skariyachan, Sinosh

    2017-01-01

    One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV), a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO) to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics), and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection. PMID:28959246

  4. 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

  5. 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

    2016-07-01

    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 will

  6. Non-clinical safety assessment of single and repeated intramuscular administration of a human papillomavirus-16/18 vaccine in rabbits and rats.

    Science.gov (United States)

    Segal, Lawrence; Morelle, Danielle; Kaaber, Kari; Destexhe, Eric; Garçon, Nathalie

    2015-12-01

    The human papillomavirus (HPV)-16/18 vaccine (Cervarix®) is a prophylactic vaccine for the prevention of cervical cancer. The vaccine contains recombinant virus-like particles assembled from the L1 major capsid proteins of the cervical cancer-causing viral types HPV-16 and HPV-18, and Adjuvant System 04 (AS04), which contains the immunostimulant MPL and aluminium salt. To evaluate potential local and systemic toxic effects of the HPV-16/18 vaccine or AS04 alone, three repeated-dose studies were performed in rabbits and rats. One rabbit study also included a single-dose evaluation. In rabbits (~2.5 kg), the full human dose (HD) of the vaccine was evaluated (0.5 ml per injection site), and in rats (~250 g), 1/5 HD of vaccine was evaluated, corresponding to ≥ 12 times the dosage in humans relative to body weight. In both animal models, the treatment-related changes included a slight transient increase in the number of circulating neutrophils as well as a local inflammatory reaction at the injection site. These treatment-related changes were less pronounced after four doses of AS04 alone than after four doses of the HPV-16/18 vaccine. Additional treatment-related changes in the rat included lower albumin/globulin ratios and microscopic signs of inflammation in the popliteal lymph nodes. In both animal models, 13 weeks after the fourth dose, recovery was nearly complete, although at the injection site in some animals there were signs of discoloration, muscle-fibre regeneration and focal points of macrophage infiltration. Therefore, in these non-clinical models, the single and repeated dose administrations of the HPV-16/18 vaccine or AS04 alone were safe and well tolerated. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Effect of vaccination against sub-clinical Porcine Circovirus type 2 infection in a high-health finishing pig herd

    DEFF Research Database (Denmark)

    Nielsen, Gitte Blach; Nielsen, Jens Peter; Haugegaard, John

    2017-01-01

    different with an average of 2.75 and 2.76 feeding units/kg gain for vaccinated and control pigs, respectively (p = 0.598). The proportion of pigs treated by injection with an antimicrobial was lower in the vaccinated group (4.4%) compared to the non-vaccinated group (5.6%), but the difference...

  8. Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.

    Science.gov (United States)

    Skeiky, Yasir A W; Dietrich, Jes; Lasco, Todd M; Stagliano, Katherine; Dheenadhayalan, Veerabadran; Goetz, Margaret Ann; Cantarero, Luis; Basaraba, Randall J; Bang, Peter; Kromann, Ingrid; McMclain, J Bruce; Sadoff, Jerald C; Andersen, Peter

    2010-01-22

    Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.

  9. Hookworm vaccines.

    Science.gov (United States)

    Diemert, David J; Bethony, Jeffrey M; Hotez, Peter J

    2008-01-15

    Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.

  10. Mucosal vaccines

    Science.gov (United States)

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921

  11. Clinical Trial Results of the HER-2/neu (E75) Vaccine to Prevent Breast Cancer Recurrence in High-Risk Patients

    Science.gov (United States)

    Mittendorf, Elizabeth A.; Clifton, Guy T.; Holmes, Jarrod P.; Clive, Kevin S.; Patil, Ritesh; Benavides, Linda C.; Gates, Jeremy D.; Sears, Alan K.; Stojadinovic, Alexander; Ponniah, Sathibalan; Peoples, George E.

    2012-01-01

    BACKGROUND The authors conducted exploratory phase 1–2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3–restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS). METHODS These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3+) expressing tumors. HLA-A2/A3+ patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests. RESULTS Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred. CONCLUSIONS The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted. PMID:21989902

  12. Vaccinations for the Older Adult.

    Science.gov (United States)

    Gnanasekaran, Gowrishankar; Biedenbender, Rex; Davidson, Harley Edward; Gravenstein, Stefan

    2016-08-01

    Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Biomarker Tools to Design Clinical Vaccines Determined from a Study of Annual Listeriosis Incidence in Northern Spain

    Science.gov (United States)

    Calderon-Gonzalez, Ricardo; Teran-Navarro, Hector; Marimon, José María; González-Rico, Claudia; Calvo-Montes, Jorge; Frande-Cabanes, Elisabet; Alkorta-Gurrutxaga, Miriam; Fariñas, M. C.; Martínez-Martínez, Luis; Perez-Trallero, Emilio; Alvarez-Dominguez, Carmen

    2016-01-01

    Two regions of northern Spain, Gipuzkoa, and Cantabria present high annual incidence of listeriosis (1.86 and 1.71 cases per 100,000 inhabitants, respectively). We report that the high annual incidences are a consequence of infection with highly virulent Listeria monocytogenes isolates linked to fatal outcomes in elderly patients with cancer. In addition, listeriosis patients with cancer present low IL-17A/IL-6 ratios and significantly reduced levels of anti-GAPDH1–22 antibodies, identified as two novel biomarkers of poor prognosis. Analysis of these biomarkers may aid in reducing the incidence of listeriosis. Moreover, GAPDH1–22-activated monocyte-derived dendritic cells of listeriosis patients with cancer seem useful tools to prepare clinical vaccines as they produce mainly Th1 cytokines. PMID:27965668

  14. Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Mohammad Ali

    2016-09-01

    Full Text Available Vaccinating a buffer of individuals around a case (ring vaccination has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE of oral cholera vaccines (OCVs for such a strategy.This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5

  15. BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial.

    Science.gov (United States)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter; Benn, Christine Stabell; Greisen, Gorm; Jeppesen, Dorthe Lisbeth; Birk, Nina Marie; Kjærgaard, Jesper; Nissen, Thomas Nørrelykke; Pihl, Gitte Thybo; Thøstesen, Lisbeth Marianne; Kofoed, Poul-Erik; Pryds, Ole; Ravn, Henrik

    2017-03-01

    The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population. NCT01694108, results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    NARCIS (Netherlands)

    Moorthy, V.S.; Diggs, C.; Ferro, S.; Good, M.F.; Herrera, S.; Hill, A.V.; Imoukhuede, E.B.; Kumar, S.; Loucq, C.; Marsh, K.; Ockenhouse, C.F.; Richie, T.L.; Sauerwein, R.W.

    2009-01-01

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing

  17. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and celeco...

  18. First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses.

    Science.gov (United States)

    Choi, Eunsil; Michalski, Chad J; Choo, Seung Ho; Kim, Gyoung Nyoun; Banasikowska, Elizabeth; Lee, Sangkyun; Wu, Kunyu; An, Hwa-Yong; Mills, Anthony; Schneider, Stefan; Bredeek, U Fritz; Coulston, Daniel R; Ding, Shilei; Finzi, Andrés; Tian, Meijuan; Klein, Katja; Arts, Eric J; Mann, Jamie F S; Gao, Yong; Kang, C Yong

    2016-11-28

    Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus. This genetically modified virus (gmHIV-1NL4-3) was inactivated and formulated as a killed whole-HIV vaccine, and then used for a Phase I human clinical trial (Trial Registration: Clinical Trials NCT01546818). The gmHIV-1NL4-3 was propagated in the A3.01 human T cell line followed by virus purification and inactivation with aldrithiol-2 and γ-irradiation. Thirty-three HIV-1 positive volunteers receiving cART were recruited for this observer-blinded, placebo-controlled Phase I human clinical trial to assess the safety and immunogenicity. Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV-1NL4-3-specific PCR showed neither evidence of vaccine virus replication in the vaccine virus-infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore, SAV001 with adjuvant significantly increased the pre-existing antibody response to HIV-1 proteins. Antibodies in the plasma of vaccinees were also found to recognize HIV-1 envelope protein on the surface of infected cells as well as showing an enhancement of broadly neutralizing antibodies inhibiting tier I and II of HIV-1 B, D, and A subtypes. The killed whole-HIV vaccine, SAV001, is safe and triggers anti-HIV immune responses. It remains to be determined through an appropriate trial whether this immune response prevents HIV

  19. Clinical and anti-inflammatory effects of ultra-short preseasonal vaccine to Parietaria in asthma.

    Science.gov (United States)

    Scichilone, Nicola; Scalici, Vincenza; Arrigo, Rita; Bellia, Vincenzo

    2013-08-01

    The ultra-short course preseasonal allergy vaccine, containing the adjuvant monophosphoryl lipid A (MPL), is effective in treating allergic symptoms; however, the efficacy in controlling asthmatics symptoms has not been fully demonstrated. We aimed at evaluating whether the ultra-short preseasonal course of immunotherapy contributes to asthma control. Four subcutaneous injections of the active product (Pollinex Quattro) were administered, before the pollen season, to 20 Parietaria-sensitive mild, untreated asthmatics (M/F: 12/8; age: 38 ± 14 years). After the screening visit (visit 1), asthma control was assessed by the Asthma Control Test (ACT) immediately before the first (visit 2) and immediately after the last (visit 5) injections, as well as during the pollen season (visit 6). Bronchial and alveolar exhaled nitric oxide (NO) concentrations were also measured. Nine Parietaria-sensitive mild asthmatics (M/F: 3/6; age: 40 ± 12 years) served as untreated controls. The ACT remained constant during allergen exposure in specific immunotherapy (SIT)-treated asthmatics (visit 2: 22 ± 3.2; visit 5: 23 ± 2.8; visit 6: 22 ± 3.6; analysis of variance [ANOVA], p = 0.47), whereas it dropped during pollen exposure in controls (visit 2: 20 ± 2.5; visit 5: 21 ± 2.8; visit 6: 16 ± 5.7; ANOVA, p = 0.01). The forced expiratory NO (FENO) values significantly increased during pollen exposure in both groups; however, the alveolar NO concentrations remained stable in SIT-treated asthmatics (p = 0.11), whereas they doubled in controls (p = 0.01). The current findings show that the preseasonal vaccine adjuvated with MPL contributes to the maintenance of control of asthma during the pollen season.

  20. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

    Directory of Open Access Journals (Sweden)

    Minamida Hidetoshi

    2004-06-01

    Full Text Available Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL recognized by CD8+ cytotoxic T lymphocytes (CTLs. We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2, general malaise (grade 1, and fever (grade 1. No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9 decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.

  1. Awareness and acceptance of human papillomavirus (HPV) vaccination among males attending a major sexual health clinic in Wuxi, China: A cross-sectional study.

    Science.gov (United States)

    Zou, Huachun; Meng, Xiaojun; Jia, Tianjian; Zhu, Chen; Chen, Xin; Li, Xiaolin; Xu, Junjie; Ma, Wei; Zhang, Xuan

    2016-06-02

    To study the awareness and acceptance of human papillomavirus (HPV) vaccination among sexually active men having sex with men (MSM) and men not having sex with men (MNSM) attending the largest sexual health clinic in Wuxi, China. A questionnaire about participants' socio-demographic characteristics and view on HPV vaccination was collected. A total of 186 MSM and 182 MNSM were recruited. Among MSM, 12.4% were under 20 years old, 64.5% never married and 56.5% from Jiangsu Province (where Wuxi City is located); 64.0% had resided in Wuxi for over 2 years, 64.5% had high school education or more, and 83.9% had an income of 5000 RMB or less per month compared to figures of 5.5%, 50.6%, 73.6%, 54.9%, 86.8% and 64.8% among MNSM, respectively (All P values men, 18.4% and 23.1% had heard of HPV; 10.2% and 15.4% had heard of HPV vaccine; and 26.2% and 20.2% would take HPV vaccine before sexual debut, respectively. MNSM were significantly more willing to take HPV vaccine than MSM (70.9 vs 34.9%, p HPV vaccine acceptance among MSM included engaging mostly in receptive anal sex (Odds ratio (OR)=3.9, 95% Confidence interval (CI): 1.8-13.5), never using a condom in anal sex in the past 6 months (3.5, 1.5-20.2), ever diagnosed with a sexually transmitted infection (STI) (3.4, 1.3-8.4) and ever receiving HIV related services (1.6, 1.1-4.4). Among MNSM these Factors included commercial sex with women (1.7, 1.2-8.6), never using a condom in commercial sex (1.6, 1.4-7.6) and STI diagnosis (2.0, 1.6-7.3). Sexually active MSM and MNSM in Wuxi lacked knowledge of HPV and HPV vaccination. The majority of these at-risk men would not benefit from HPV vaccination as their age at first sex proceeded perceived age of vaccine uptake. Aggressive education aimed at increasing knowledge of HPV and HPV vaccination among these men is warranted.

  2. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... caused by persistent infection and genital warts ( 22 ). Analyses of data from women participating in a clinical ... is to contact the insurance plan or the clinic. Most private insurance plans cover HPV vaccination. The ...

  3. Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines

    NARCIS (Netherlands)

    Gruijl, de Tanja; Eertwegh, van den Alfons; Pinedo, Herbert; Scheper, Rik

    2008-01-01

    The Weld of tumor vaccination is currently undergoing a shift in focus, from individualized tailor-made vaccines to more generally applicable vaccine formulations. Although primarily predicated by Wnancial and logistic considerations, stemming from a growing awareness that clinical development

  4. Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events.

    Science.gov (United States)

    Sobolev, Olga; Binda, Elisa; O'Farrell, Sean; Lorenc, Anna; Pradines, Joel; Huang, Yongqing; Duffner, Jay; Schulz, Reiner; Cason, John; Zambon, Maria; Malim, Michael H; Peakman, Mark; Cope, Andrew; Capila, Ishan; Kaundinya, Ganesh V; Hayday, Adrian C

    2016-02-01

    Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ∼35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.

  5. Marmosets (Callithrix jacchus) as a non-human primate model for evaluation of candidate dengue vaccines: induction and maintenance of specific protective immunity against challenges with clinical isolates.

    Science.gov (United States)

    Moi, Meng Ling; Ami, Yasushi; Muhammad Azami, Nor Azila; Shirai, Kenji; Yoksan, Sutee; Suzaki, Yuriko; Kitaura, Kazutaka; Lim, Chang-Kweng; Saijo, Masayuki; Suzuki, Ryuji; Takasaki, Tomohiko; Kurane, Ichiro

    2017-11-21

    Dengue virus (DENV) is one of the major infectious diseases in tropical regions and approximately half of the world population is at risk of infection. Vaccines would offer an effective control measure against this disease. We previously reported on the utility of marmosets as an animal model for studying primary and secondary dengue infections. Infected marmosets consistently develop viraemia and antibody kinetics that reflect those of patients with dengue. Thus, it is important to determine the utility of marmosets as an animal model for demonstrating vaccine efficacy. In this study, marmosets were inoculated with candidate vaccine and parent strains and challenged with a clinical DENV strain. The viraemia and antibody kinetics in these marmosets were determined. Marmosets consistently develop lower viraemia with an attenuated vaccine strain. During secondary challenge, the IgM response was delayed, whereas the IgG levels rose rapidly, indicating a secondary antibody response. The neutralizing activities against the homotypic serotype were high; all marmosets were protected against viraemia following secondary inoculation. The viraemia markers and antibody responses were consistent with those of human DENV infection and vaccinees. These results demonstrate the utility of marmosets as an animal model for the study of vaccine efficacy.

  6. Knowledge translation of the HELPinKIDS clinical practice guideline for managing childhood vaccination pain: usability and knowledge uptake of educational materials directed to new parents

    Directory of Open Access Journals (Sweden)

    Taddio Anna

    2013-02-01

    Full Text Available Abstract Background Although numerous evidence-based and feasible interventions are available to treat pain from childhood vaccine injections, evidence indicates that children are not benefitting from this knowledge. Unrelieved vaccination pain puts children at risk for significant long-term harms including the development of needle fears and subsequent health care avoidance behaviours. Parents report that while they want to mitigate vaccination pain in their children, they lack knowledge about how to do so. An evidence-based clinical practice guideline for managing vaccination pain was recently developed in order to address this knowledge-to-care gap. Educational tools (pamphlet and video for parents were included to facilitate knowledge transfer at the point of care. The objectives of this study were to evaluate usability and effectiveness in terms of knowledge acquisition from the pamphlet and video in parents of newly born infants. Methods Mixed methods design. Following heuristic usability evaluation of the pamphlet and video, parents of newborn infants reviewed revised versions of both tools and participated in individual and group interviews and individual knowledge testing. The knowledge test comprised of 10 true/false questions about the effectiveness of various pain management interventions, and was administered at three time points: at baseline, after review of the pamphlet, and after review of the video. Results Three overarching themes were identified from the interviews regarding usability of these educational tools: receptivity to learning, accessibility to information, and validity of information. Parents’ performance on the knowledge test improved (p≤0.001 from the baseline phase to after review of the pamphlet, and again from the pamphlet review phase to after review of the video. Conclusions Using a robust testing process, we demonstrated usability and conceptual knowledge acquisition from a parent-directed educational

  7. Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland

    Science.gov (United States)

    Partinen, Markku; Saarenpää-Heikkilä, Outi; Ilveskoski, Ismo; Hublin, Christer; Linna, Miika; Olsén, Päivi; Nokelainen, Pekka; Alén, Reija; Wallden, Tiina; Espo, Merimaaria; Rusanen, Harri; Olme, Jan; Sätilä, Heli; Arikka, Harri; Kaipainen, Pekka; Julkunen, Ilkka; Kirjavainen, Turkka

    2012-01-01

    Background Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002–2010. Methods All Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference. Findings Altogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002–2009 giving an annual incidence of 0.79 per 100 000 inhabitants (95% confidence interval 0.62–0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12–0.51) per 100 000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100 000; 17-fold increase). Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100 000, which equals that in 2002–2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency narcolepsy. Interpretation A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children. PMID:22470463

  8. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  9. Emerging Vaccine Informatics

    Science.gov (United States)

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    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. PMID:21772787

  10. Databases and in silico tools for vaccine design.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2013-01-01

    In vaccine design, databases and in silico tools play different but complementary roles. Databases collect experimentally verified vaccines and vaccine components, and in silico tools provide computational methods to predict and design new vaccines and vaccine components. Vaccine-related databases include databases of vaccines and vaccine components. In the USA, the Food and Drug Administration (FDA) maintains a database of licensed human vaccines, and the US Department of Agriculture keeps a database of licensed animal vaccines. Databases of vaccine clinical trials and vaccines in research also exist. The important vaccine components include vaccine antigens, vaccine adjuvants, vaccine vectors, and -vaccine preservatives. The vaccine antigens can be whole proteins or immune epitopes. Various in silico vaccine design tools are also available. The Vaccine Investigation and Online Information Network (VIOLIN; http://www.violinet.org ) is a comprehensive vaccine database and analysis system. The VIOLIN database includes various types of vaccines and vaccine components. VIOLIN also includes Vaxign, a Web-based in silico vaccine design program based on the reverse vaccinology strategy. Vaccine information and resources can be integrated with Vaccine Ontology (VO). This chapter introduces databases and in silico tools that facilitate vaccine design, especially those in the VIOLIN system.

  11. Vaccination coverage among adults, excluding influenza vaccination - United States, 2013.

    Science.gov (United States)

    Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Bridges, Carolyn B; Kim, David K; Pilishvili, Tamara; Hales, Craig M; Markowitz, Lauri E

    2015-02-06

    among the general population, and adult patients largely rely on health care provider recommendations for vaccination. The Community Preventive Services Task Force and the National Vaccine Advisory Committee have recommended that health care providers incorporate vaccination needs assessment, recommendation, and offer of vaccination into every clinical encounter with adult patients to improve vaccination rates and to narrow the widening racial/ethnic disparities in vaccination coverage.

  12. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  13. European Vaccine Initiative: lessons from developing malaria vaccines.

    Science.gov (United States)

    Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

    2011-12-01

    For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

  14. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjærgaard, Jesper

    2016-01-01

    and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. MAIN OUTCOME AND MEASURE: Trial-registered adverse reactions after BCG...... vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. RESULTS: Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional...... cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value

  15. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland.

    Directory of Open Access Journals (Sweden)

    Markku Partinen

    Full Text Available BACKGROUND: Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002-2010. METHODS: All Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference. FINDINGS: Altogether 335 cases (all ages of narcolepsy were diagnosed in Finland during 2002-2009 giving an annual incidence of 0.79 per 100,000 inhabitants (95% confidence interval 0.62-0.96. The average annual incidence among subjects under 17 years of age was 0.31 (0.12-0.51 per 100,000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100,000; 17-fold increase. Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100,000, which equals that in 2002-2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42 before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency <8 min and ≥2 sleep onset REM periods. The symptoms started abruptly. Forty-seven (94% had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy. INTERPRETATION: A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children.

  16. A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3

    Science.gov (United States)

    Greenfield, William W; Stratton, Shawna L; Myrick, Rebecca S; Vaughn, Rita; Donnalley, Lisa M; Coleman, Hannah N; Mercado, Maria; Moerman-Herzog, Andrea M; Spencer, Horace J; Andrews-Collins, Nancy R; Hitt, Wilbur C; Low, Gordon M; Manning, Nirvana A; McKelvey, Samantha S; Smith, Dora; Smith, Michael V; Phillips, Amy M; Quick, C Matthew; Jeffus, Susanne K; Hutchins, Laura F; Nakagawa, Mayumi

    2015-01-01

    PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted. PMID:26451301

  17. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.

    Science.gov (United States)

    Modjarrad, Kayvon; Lin, Leyi; George, Sarah L; Stephenson, Kathryn E; Eckels, Kenneth H; De La Barrera, Rafael A; Jarman, Richard G; Sondergaard, Erica; Tennant, Janice; Ansel, Jessica L; Mills, Kristin; Koren, Michael; Robb, Merlin L; Barrett, Jill; Thompson, Jason; Kosel, Alison E; Dawson, Peter; Hale, Andrew; Tan, C Sabrina; Walsh, Stephen R; Meyer, Keith E; Brien, James; Crowell, Trevor A; Blazevic, Azra; Mosby, Karla; Larocca, Rafael A; Abbink, Peter; Boyd, Michael; Bricault, Christine A; Seaman, Michael S; Basil, Anne; Walsh, Melissa; Tonwe, Veronica; Hoft, Daniel F; Thomas, Stephen J; Barouch, Dan H; Michael, Nelson L

    2017-12-04

    A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings. We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233. We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies. The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults. Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  19. Shigella sonnei Vaccine Candidates WRSs2 and WRSs3 Are as Immunogenic as WRSS1, a Clinically Tested Vaccine Candidate, in a Primate Model of Infection

    Science.gov (United States)

    2011-01-01

    Brown AW, Wallace SM, Jones E, Asher LV, Pattarini D, et al. Immune response to and histopathology of Campylobacter jejuni infection in ferrets...WRSs3 a b s t r a c t Shigella causes diarrhea and dysentery through contaminated food and water. Shigella sonnei live vaccine...results in diarrhea , fever, dysentery and considerable gastrointestinal and constitutional symptoms. The low infective dose of 10–100 bacteria, and high

  20. Tuberculosis vaccine development: recent progress.

    Science.gov (United States)

    Orme, I M; McMurray, D N; Belisle, J T

    2001-03-01

    Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.

  1. Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402

    Directory of Open Access Journals (Sweden)

    Baba Toshiyuki

    2010-09-01

    Full Text Available Abstract Background The tumor associated antigen (TAA gp100 was one of the first identified and has been used in clinical trials to treat melanoma patients. However, the gp100 epitope peptide restricted to HLA-A*2402 has not been extensively examined clinically due to the ethnic variations. Since it is the most common HLA Class I allele in the Japanese population, we performed a phase I clinical trial of cancer vaccination using the HLA-A*2402 gp100 peptide to treat patients with metastatic melanoma. Methods The phase I clinical protocol to test a HLA-A*2402 gp100 peptide-based cancer vaccine was designed to evaluate safety as the primary endpoint and was approved by The University of Tokyo Institutional Review Board. Information related to the immunologic and antitumor responses were also collected as secondary endpoints. Patients that were HLA-A*2402 positive with stage IV melanoma were enrolled according to the criteria set by the protocol and immunized with a vaccine consisting of epitope peptide (VYFFLPDHL, gp100-in4 emulsified with incomplete Freund's adjuvant (IFA for the total of 4 times with two week intervals. Prior to each vaccination, peripheral blood mononuclear cells (PBMCs were separated from the blood and stored at -80°C. The stored PBMCs were thawed and examined for the frequency of the peptide specific T lymphocytes by IFN-γ- ELISPOT and MHC-Dextramer assays. Results No related adverse events greater than grade I were observed in the six patients enrolled in this study. No clinical responses were observed in the enrolled patients although vitiligo was observed after the vaccination in two patients. Promotion of peptide specific immune responses was observed in four patients with ELISPOT assay. Furthermore, a significant increase of CD8+ gp100-in4+ CTLs was observed in all patients using the MHC-Dextramer assay. Cytotoxic T lymphocytes (CTLs clones specific to gp100-in4 were successfully established from the PBMC of some

  2. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  3. Rotavirus vaccines: an update.

    Science.gov (United States)

    Dennehy, Penelope H

    2005-02-01

    Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

  4. [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.

  5. Vaccines and Kawasaki disease.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  6. Efficacy of a polyvalent mastitis vaccine against Staphylococcus aureus on a dairy Mediterranean buffalo farm: results of two clinical field trials.

    Science.gov (United States)

    Guccione, Jacopo; Pesce, Antonella; Pascale, Massimo; Salzano, Caterina; Tedeschi, Gianni; D'Andrea, Luigi; De Rosa, Angela; Ciaramella, Paolo

    2017-01-19

    In the last years the knowledges on Mediterranean Buffalo (MB) mastitis is remarkably improving, nevertheless the attention has been never focused on vaccination as preventive strategy for the control of mastitis in these ruminates. The aim of the current study was to assess clinical efficacy over time of two different preventive vaccination protocols against S. aureus mastitis, in primiparous MB.Vaccinated (VG) and not-vaccinated (N-VG) groups, of 30 MB each one, were selected from two different herds (herd A: VG1 and N-VG1; herd B: VG2 and N-VG2) of the same farm. Herd A received a double vaccination (Startvac®, 45 and 10 days before calving, protocol A), while in herd B an additional administration was performed (52 days after calving, protocol B). Bacteriological milk culture and assessment of somatic cell count (SCC) were performed at 10, 30, 60 and 90 days in milk (DIM) from composite milk samples. After 90 DIM, daily milk yields and SCC values were monthly detected until dry-off. The overall incidence of positive MB for S. aureus was 40.8% (49/120) in VG1 and 43.3% (52/120) in N-VG1 (Protocol A), while 45.8% (55/120) and 50.8% (61/120) in VG2 and N-VG2 (Protocol B). The latter was associated with a significant decreased in prevalence (at 90 DIM) and incidence of mastitis (animals positive for S. aureus, SCC > 200^10 3 , with or without clinical signs) in the vaccinated MB, while no difference occurred in protocol A. Moreover, herd B showed a significant reduction in prevalence of intramammary infection (animals positive for S. aureus, SCC mastitis and somatic cell count; the polyvalent mastitis vaccine may be considered an additional tool for in-herd S aureus infection and should be associated to other control procedures to maximize its properties.

  7. Measles, mumps, and rubella virus vaccine (M-M-R™II): a review of 32 years of clinical and postmarketing experience.

    Science.gov (United States)

    Lievano, Fabio; Galea, Susan A; Thornton, Michele; Wiedmann, Richard T; Manoff, Susan B; Tran, Trung N; Amin, Manisha A; Seminack, Margaret M; Vagie, Kristen A; Dana, Adrian; Plotkin, Stanley A

    2012-11-06

    M-M-R™II (measles, mumps, and rubella virus vaccine live; Merck, Sharp, & Dohme Corp.) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals ≥ 12 months of age. Before the vaccine era, these viruses infected most exposed individuals, with subsequent morbidity and mortality. One of the greatest achievements of public health has been to eliminate these 3 diseases in large geographic areas. The safety profile of M-M-R™II is described using data from routine global postmarketing surveillance. Postmarketing surveillance has limitations (including incomplete reporting of case data), but allows collection of real-world information on large numbers of individuals, who may have concurrent medical problems excluding them from clinical trials. It can also identify rare adverse experiences (AEs). Over its 32-year history, ≈ 575 million doses of M-M-R™II have been distributed worldwide, with 17,536 AEs voluntarily reported for an overall rate of 30.5 AEs/1,000,000 doses distributed. This review provides evidence that the vaccine is safe and well-tolerated. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial.

    Science.gov (United States)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper; Hartling, Hans Jacob; Thøstesen, Lisbeth Marianne; Kofoed, Poul-Erik; Stensballe, Lone Graff; Andersen, Andreas; Pryds, Ole; Netea, Mihai G; Benn, Christine Stabell; Nielsen, Susanne Dam; Jeppesen, Dorthe Lisbeth

    2017-09-29

    The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4 + T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8 + T cells), and reduced proportions of late differentiated CD4 + T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4 + T cells at 13 months (GMR = 0.55, 95% CI (0.32-0.92), p = 0.03). In conclusion, limited overall impact of neonatal BCG vaccination on lymphocyte subsets was found in healthy Danish infants within the first 13 months of life. This is in line with the limited clinical effects of BCG observed in our setting.

  9. Vaccination coverage in a cohort of HIV-infected patients receiving care at an AIDS outpatient clinic in Espírito Santo, Brazil

    Directory of Open Access Journals (Sweden)

    Lauro Ferreira da Silva Pinto Neto

    2017-09-01

    Full Text Available This cross-sectional study assessed the immunization status of human immune deficiency virus (HIV-infected patients receiving care at an outpatient clinic in Brazil. The sociodemographic characteristics, CD4 count and HIV viral load of 281 out of 612 adult outpatients were analyzed. A total of 331 patients were excluded because of no availability of vaccination cards. Chi-square or Fisher's exact test were used. Immunization coverage was higher for diphtheria/tetanus (59.79% and hepatitis B (56.7%, and lowest for hepatitis A (6.8% and for meningococcal group C (6%. Only 11.74% of the patients had received the influenza virus vaccine yearly since their HIV-infection diagnosis. No vaccination against influenza (p < 0.034 or hepatitis B (p < 0.029 were associated with CD4 counts <500 cells/mL; no vaccination against flu or pneumococcus were associated with detectable HIV viral load (p < 0.049 and p < 0.002, respectively. Immunization coverage is still very low among HIV-infected adults in this setting despite recommendations and high infection-related mortality.

  10. Vaccination coverage in a cohort of HIV-infected patients receiving care at an AIDS outpatient clinic in Espírito Santo, Brazil

    Directory of Open Access Journals (Sweden)

    Lauro Ferreira da Silva Pinto Neto

    Full Text Available Abstract This cross-sectional study assessed the immunization status of human immune deficiency virus (HIV-infected patients receiving care at an outpatient clinic in Brazil. The sociodemographic characteristics, CD4 count and HIV viral load of 281 out of 612 adult outpatients were analyzed. A total of 331 patients were excluded because of no availability of vaccination cards. Chi-square or Fisher's exact test were used. Immunization coverage was higher for diphtheria/tetanus (59.79% and hepatitis B (56.7%, and lowest for hepatitis A (6.8% and for meningococcal group C (6%. Only 11.74% of the patients had received the influenza virus vaccine yearly since their HIV-infection diagnosis. No vaccination against influenza (p < 0.034 or hepatitis B (p < 0.029 were associated with CD4 counts <500 cells/mL; no vaccination against flu or pneumococcus were associated with detectable HIV viral load (p < 0.049 and p < 0.002, respectively. Immunization coverage is still very low among HIV-infected adults in this setting despite recommendations and high infection-related mortality.

  11. Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia.

    Science.gov (United States)

    Aljunid, Syed; Abuduxike, Gulifeiya; Ahmed, Zafar; Sulong, Saperi; Nur, Amrizal Muhd; Goh, Adrian

    2011-09-21

    Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).

  12. Clinical testing of an inactivated influenza A/H5N1 vaccine candidate in a double-blinded, placebo-controlled, randomized trial in healthy adults in Vietnam.

    Science.gov (United States)

    Phan, Trong Lan; Ho, Vinh Thang; Vu, Minh Huong; Nguyen, Tuyet Nga; Duong, Huu Thai; Holt, Renee; Wahid, Rahnuma; Donnelly, John; Flores, Jorge

    2016-10-26

    We tested an inactivated egg-grown whole virus influenza A/H5N1 vaccine candidate developed by the Institute of Vaccines and Medical Biologicals (IVAC), a state-run vaccine manufacturer in Vietnam, in a Phase 1, placebo controlled, double blinded, randomized trial. The vaccine was adjuvanted with aluminum hydroxide. The trial enrolled 75 subjects who were randomized to receive two injections of one of the following: low-dose of vaccine (7.5 mcg HA), high-dose of vaccine (15 mcg HA), or placebo. The vaccine candidate was well tolerated with minimal local reactogenicity consisting of mild, short-lived injection site pain and/or tenderness. No systemic reactogenicity was observed other than transient low-grade fever in about 13% of the subjects and no unsolicited adverse events were attributable to product administration. Immune responses were assessed at baseline and after the first and second dose by hemagglutination inhibition (HAI) and microneutralization (MN) assays, with 72% of the high-dose and 68% of the low-dose vaccine recipients presenting a ⩾4-fold response in the HAI assay and 72% of the high-dose and 61% of the low-dose vaccine recipients exhibiting a ⩾4-fold response in the MN assay. These promising results support further development. ClinicalTrials.gov number NCT02171819, June 20, 2014. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors.

    Directory of Open Access Journals (Sweden)

    Susanne H Sheehy

    Full Text Available Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question.We conducted a Phase Ia, non-randomized clinical trial in 16 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63 and modified vaccinia virus Ankara (MVA replication-deficient viral vectored vaccines encoding two alleles (3D7 and FVO of the P. falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1. ChAd63-MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to both alleles 3D7 (median 2036 SFU/million PBMC and FVO (median 1539 SFU/million PBMC, with a mixed CD4(+/CD8(+ phenotype, as well as substantial AMA1-specific serum IgG responses (medians of 49 µg/mL and 41 µg/mL for 3D7 and FVO AMA1 respectively that demonstrated growth inhibitory activity in vitro.ChAd63-MVA is a safe and highly immunogenic delivery platform for both alleles of the AMA1 antigen in humans which warrants further efficacy testing. ChAd63-MVA is a promising heterologous prime-boost vaccine strategy that could be applied to numerous other diseases where strong cellular and humoral immune responses are required for protection.ClinicalTrials.gov NCT01095055.

  14. Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research.

    Science.gov (United States)

    Wieczorek, Lindsay; Krebs, Shelly J; Kalyanaraman, Vaniambadi; Whitney, Stephen; Tovanabutra, Sodsai; Moscoso, Carlos G; Sanders-Buell, Eric; Williams, Constance; Slike, Bonnie; Molnar, Sebastian; Dussupt, Vincent; Alam, S Munir; Chenine, Agnes-Laurence; Tong, Tina; Hill, Edgar L; Liao, Hua-Xin; Hoelscher, Michael; Maboko, Leonard; Zolla-Pazner, Susan; Haynes, Barton F; Pensiero, Michael; McCutchan, Francine; Malek-Salehi, Shawyon; Cheng, R Holland; Robb, Merlin L; VanCott, Thomas; Michael, Nelson L; Marovich, Mary A; Alving, Carl R; Matyas, Gary R; Rao, Mangala; Polonis, Victoria R

    2015-08-01

    Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of cross-subtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine. At present, the product pipeline for HIV vaccines is insufficient and is limited by inadequate capacity to produce large quantities of vaccine to standards required for human clinical trials. Such products are required to evaluate critical questions of vaccine formulation, route, dosing, and schedule, as well as to establish vaccine efficacy. The gp145 Env protein presented in this study forms physical trimers, binds to many of the

  15. CHARACTERISATION OF CELL-MEDIATED IMMUNE RESPONSE IN PIGS IN A CLINICAL CHALLENGE EXPERIMENT OF A VACCINE AGAINST MYCOPLASMA HYOSYNOVIAE

    DEFF Research Database (Denmark)

    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll

    Mycoplasma hyosynoviae (Mhs) is an extracellular parasitizing bacterium that causes arthritis in swine. The infection is widespread in modern pig production. An effective immunoprophylaxis is not available. In an experimental infection study (Lauritsen, K. T., et al., 2009. 3rd EVIW Poster, Berlin...... (Germany) September 10-13, 2009), testing a new vaccine (formalin inactivated Mhs and EMULSIGEN-BCL® (MVP Laboratories)), cell-mediated immune response was measured in the vaccine group (n=13) and not in the placebo group (n=13). In an IFN-γ assay, where whole-blood was co-cultured with Mhs......-antigen and recombinant IL-18, significantly higher level of IFN-γ was produced in the vaccine group compared to the placebo group one day before challenge with Mhs. In contrast, significantly higher level of IFN-γ was measured in the placebo group compared to the vaccine group at day 6 after challenge. The latter could...

  16. Estimation of the variation that can be attributed to different levels in a clinical trial of a vaccine

    DEFF Research Database (Denmark)

    Garcia Clavero, Ana Belén; Bahrndorff, Simon; Hald, Birthe

    2012-01-01

    This presentation is focusing on the interaction between the experimental design of a vaccination trial and appropriate data analysis using a trial of a vaccine against Campylobacter in broilers as an example. This study was designed using four rotations with eight isolators per rotation (10...... chickens per isolator). Treatment was administered at isolator level on day 14 (vaccine or placebo). The broilers were inoculated with Campylobacter jejuni at day 31 and slaughtered at day 42. The numbers of Campylobacter (cfu/g) were obtained in the laboratory using selective cultivation methods and log...... transformed to obtain a Gaussian distribution. Initially, the effect of the vaccine was analyzed using all data in a t-test. Subsequently, the t-test was stratified by rotation. Finally, mixed linear models were used, taking into account the physical hierarchical setup of the trial. Results from the t...

  17. Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

    Science.gov (United States)

    Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

    2014-01-01

    Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

  18. Immunolipoplexes: an efficient, nonviral alternative for transfection of human dendritic cells with potential for clinical vaccination.

    Science.gov (United States)

    Tan, Peng H; Beutelspacher, Sven C; Wang, Yao-He; McClure, Myra O; Ritter, Mary A; Lombardi, Giovanna; George, Andrew J T

    2005-05-01

    Genetic manipulation of dendritic cells (DCs) is important in the context of using either mature DCs to immunize patients or immature DCs to induce tolerance. Here, we describe a novel method of transfecting monocyte-derived human DCs using immunolipoplexes containing anti-CD71 or anti-CD205 monoclonal Abs. This results in up to 20% transfection, which can be increased to 20-30% if the immunolipoplexes are used to transfect CD14+ monocytes prior to differentiation into DCs. Transfected DCs can be substantially enriched using a drug-selection protocol during differentiation. Unlike adenoviral transduction, this nonviral transfection does not alter the expression of costimulatory molecules or the production of proinflammatory cytokines by DCs. In addition, DC function is unaltered, as assessed by mixed lymphocyte reactions. To test the feasibility of the immunolipoplexes and selection protocol for therapeutic intervention, we transfected DCs with the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Allogeneic T cells exposed to IDO-expressing DCs did not proliferate, secreted more IL-10 and less Th1 and Th2 cytokines, and had a higher amount of apoptosis than T cells incubated with control DCs. Furthermore the remaining T cells were rendered anergic to further stimulation by allogeneic DC. These immunolipoplexes, which can be easily and rapidly assembled, have potential for clinical immunization, in particular for tolerance induction protocols.

  19. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  20. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, M; Met, Ö; Svane, I M

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  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. Rotavirus vaccines--an update.

    Science.gov (United States)

    Kirkwood, Carl D; Buttery, Jim

    2003-02-01

    Rotavirus vaccines offer the best hope to reduce the toll of acute rotaviral gastroenteritis in both developed and developing countries. An association with intussusception (IS) led to the withdrawal of the first licensed rotavirus vaccine in the USA in 1999, forcing a re-evaluation of the safety profile of potentially lifesaving vaccines. Development of new rotavirus vaccine candidates has continued, with a bovine-human reassortant vaccine and an attenuated human monovalent vaccine commencing Phase III trials. Several other candidates are in early Phase I and II clinical trials. The creation of innovative funding strategies to support vaccine development and production, specifically in developing countries, aim to make vaccines available where rotavirus causes the greatest impact.

  3. Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life: A randomized clinical trial.

    Science.gov (United States)

    Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo; Kjærgaard, Jesper; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Jensen, Aksel Karl Georg; Aaby, Peter; Olesen, Annette Wind; Jeppesen, Dorthe Lisbeth; Benn, Christine Stabell; Kofoed, Poul-Erik

    2017-12-01

    Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a T H 2 to a T H 1 response has been suggested as a possible explanation. We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Neonatal BCG had no effect on the development of RW before 13 months of age. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Emerging human papillomavirus vaccines

    Science.gov (United States)

    Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

  5. The Human Hookworm Vaccine.

    Science.gov (United States)

    Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K

    2013-04-18

    Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The administration of a single dose of a multivalent (DHPPiL4R vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV.

  7. Multiple Vaccinations: Friend or Foe

    Science.gov (United States)

    Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

    2013-01-01

    Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

  8. Redefining the technical and organizational competences of children vaccination clinics in order to improve performance. A practical experience at the ULSS 12 Venetian Public Health and Hygiene Service

    National Research Council Canada - National Science Library

    Capretta, F; Palazzi, B; Burmaz, T; Cuccarolo, G; Flora, M E; Selle, V; Cocchio, S; Baldo, V

    2014-01-01

    Since Regione Veneto suspended compulsory vaccination for children in 2008, and because of an increasing disaffection of parents to the vaccine practice, the vaccination rates have been slowly but steadily decreasing...

  9. A Novel Use of a Statewide Telecolposcopy Network for Recruitment of Participants in a Phase I Clinical Trial of a Human Papillomavirus Therapeutic Vaccine

    Science.gov (United States)

    Stratton, Shawna L.; Spencer, Horace J.; Greenfield, William W.; Low, Gordon; Hitt, W. Chuck; Quick, Charles M.; Jeffus, Susanne K.; Blackmon, Victoria; Nakagawa, Mayumi

    2015-01-01

    Background Historically, recruitment and retention of young women in intervention-based clinical trials has been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus (HPV) therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single arm, single institution, dose-escalation Phase I clinical trial. Women with recent Papanicolau smear results showing high-grade squamous intraepithelial lesions (HSILs) or cannot rule out HSIL were eligible to enroll. Patients with biopsy-confirmed HSIL were also eligible. Colposopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of HSIL was confirmed with biopsy and other inclusion criteria were met. Purpose The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. Methods Potential vaccine candidates were recruited through direct advertisement as well as referrals, including through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention including face-to-face contact with the study coordinator at the time of consent and most of study visits, frequent contact using text messaging, phone calls, and e-mails, and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention. Results Thirty-seven participants were

  10. Recommended immunization schedules for adults: Clinical practice guidelines by the Escmid Vaccine Study Group (EVASG), European Geriatric Medicine Society (EUGMS) and the World Association for Infectious Diseases and Immunological Disorders (WAidid).

    Science.gov (United States)

    Esposito, Susanna; Bonanni, Paolo; Maggi, Stefania; Tan, Litjan; Ansaldi, Filippo; Lopalco, Pier Luigi; Dagan, Ron; Michel, Jean-Pierre; van Damme, Pierre; Gaillat, Jacques; Prymula, Roman; Vesikari, Timo; Mussini, Cristina; Frank, Uwe; Osterhaus, Albert; Celentano, Lucia Pastore; Rossi, Marta; Guercio, Valentina; Gavazzi, Gaetan

    2016-07-02

    Rapid population aging has become a major challenge in the industrialized world and progressive aging is a key reason for making improvement in vaccination a cornerstone of public health strategy. An increase in age-related disorders and conditions is likely to be seen in the near future, and these are risk factors for the occurrence of a number of vaccine-preventable diseases. An improvement in infectious diseases prevention specifically aimed at adults and the elderly can therefore also decrease the burden of these chronic conditions by reducing morbidity, disability, hospital admissions, health costs, mortality rates and, perhaps most importantly, by improving the quality of life. Among adults, it is necessary to identify groups at increased risk of vaccine-preventable diseases and highlight the epidemiological impact and benefits of vaccinations using an evidence-based approach. This document provides clinical practice guidance on immunization for adults in order to provide recommendations for decision makers and healthcare workers in Europe. Although immunization is considered one of the most impactful and cost-effective public health measures that can be undertaken, vaccination coverage rates among adults are largely lower than the stated goal of ≥ 95% among adults, and stronger efforts are needed to increase coverage in this population. Active surveillance of adult vaccine-preventable diseases, determining the effectiveness of the vaccines approved for marketing in the last 5 y, the efficacy and safety of vaccines in immunocompromised patients, as well as in pregnant women, represent the priorities for future research.

  11. Polio Vaccine

    Science.gov (United States)

    ... doctorMost kids have no problems with the polio vaccine. However, call your doctor if your child has any reaction after getting the vaccine. Call ... Tell the doctor when (day and time) your child received the vaccine. You also should file a Vaccine Adverse Event ...

  12. 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.

    Science.gov (United States)

    Kubavat, A H; Mittal, R; Patel, P M; Jarsaniya, D H; Pawar, P R

    2011-01-01

    The pandemic of H1N1 2009 influenza has spread world over and low degree of virus transmission has continued in several regions of India. To assess the immunogenicity and safety of Pandemic Influenza (H1N1) 2009 Monovalent Vaccine in healthy adult Indian population. Prospective, open label, multicentric, phase 2/3 clinical trial. 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. 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. 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 (Ppopulation.

  13. Vaccination Perceptions of College Students: With and without Vaccination Waiver

    Directory of Open Access Journals (Sweden)

    Emmanuel D. Jadhav

    2018-02-01

    Full Text Available IntroductionThe resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination.MethodsYoung adults (n = 964 from a Midwestern rural university responded to a survey (fall 2015—spring 2016 designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann–Whitney U-tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017.ResultsA little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination.ConclusionYoung adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.

  14. Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

    Science.gov (United States)

    Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

    2017-04-01

    Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ε-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

  15. Acceptability of Aujeszky's disease vaccines.

    Science.gov (United States)

    Kimman, T G

    1992-01-01

    Vaccines against Aujeszky's disease are not only used to prevent the clinical consequences of a field infection, but also to support eradication of the virus. The current Aujeszky's disease vaccines (ADV) protect against severe clinical signs of disease and they reduce but usually do not prevent virus multiplication and excretion or the establishment of latency after infection. Vaccines also limit virus multiplication after reactivation. The efficacy of vaccination is reduced by passively acquired maternal antibodies. The mechanisms that afford immunity to the virus are only poorly understood. No simple parameters for immunity are therefore available. The European Pharmacopoeia formulates requirements for inactivated and live ADV vaccines for parenteral use. The vaccines must be safe; they must not induce local or systemic reactions; they must not be transmitted to unvaccinated pigs; they must not be transmitted by semen and across the placenta; the attenuation must be irreversible (live vaccines); the inactivation must be complete (inactivated vaccines); they must prevent mortality and limit growth retardation after challenge infection; the vaccine must not contain contaminating micro-organisms and viruses. No requirements have been formulated with regard to reduction of excretion of challenge virus after experimental infection, efficacy in pigs with maternal antibodies, reproducibility of efficacy studies, reduction of virus transmission under field conditions, the presence of a serological marker, safety for other species, and safety and efficacy of intranasally administered vaccines. Future developments should be directed to the development and evaluation of ADV vaccines that are able to limit transmission of the virus.

  16. Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

    Science.gov (United States)

    Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valueeducation and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica.

    Science.gov (United States)

    Herrero, Rolando; Hildesheim, Allan; Rodríguez, Ana C; Wacholder, Sholom; Bratti, Concepción; Solomon, Diane; González, Paula; Porras, Carolina; Jiménez, Silvia; Guillen, Diego; Morales, Jorge; Alfaro, Mario; Cyr, Jean; Morrisey, Kerrygrace; Estrada, Yenory; Cortés, Bernal; Morera, Lidia Ana; Freer, Enrique; Schussler, John; Schiller, John; Lowy, Douglas; Schiffman, Mark

    2008-09-02

    We report the rationale, design, methods and details of participation of a community-based, double-blind, randomized clinical trial of an HPV 16 and 18 vaccine conducted in two provinces of Costa Rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. More than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7466 women (30% of those pre-screened, 59% of those eligible) who were randomized to receive 3 doses of the HPV vaccine or hepatitis A vaccine as control. A complex protocol of data and specimen collection was applied, including an interview, pelvic exam for sexually active women, blood for serology and cell-mediated immunity, cervical secretions for local immunity and cells for HPV, Chlamydia trachomatis and gonorrhea testing. Eighty percent of the women received three doses, 12.4% two doses and 7.4% one dose. At visits, compliance with data and specimen collection was close to 100%. Baseline characteristics and age-specific prevalence of HPV and cervical neoplasia are reported. Overall prevalence of HPV was high (50%), with 8.3% of women having HPV 16 and 3.2% HPV 18. LSIL was detected in 12.7% of women at baseline and HSIL in 1.9%. Prevalence of Chlamydia was 14.2%. There was very good agreement in HPV detection between clinician-collected and self- collected specimens (89.4% agreement for all types, kappa 0.59). Follow up will continue with yearly or more frequent examinations for at least 4 years for each participant.

  18. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.

    Directory of Open Access Journals (Sweden)

    Neal Van Hoeven

    Full Text Available West Nile virus (WNV is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE or aluminum hydroxide (Alum formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development.

  19. Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica

    Science.gov (United States)

    Herrero, Rolando; Hildesheim, Allan; Rodríguez, Ana C; Wacholder, Sholom; Bratti, Concepción; Solomon, Diane; González, Paula; Porras, Carolina; Jiménez, Silvia; Guillen, Diego; Morales, Jorge; Alfaro, Mario; Cyr, Jean; Morrisey, Kerrygrace; Estrada, Yenory; Cortés, Bernal; Morera, Lidia Ana; Freer, Enrique; Schussler, John; Schiller, John; Lowy, Douglas; Schiffman, Mark

    2008-01-01

    We report the rationale, design, methods and details of participation of a community-based, double blind, randomized clinical trial of an HPV 16 and 18 vaccine conducted in two provinces of Costa Rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. More than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7,466 women (30% of those prescreened, 59% of those eligible) who were randomized to receive 3 doses of the HPV vaccine or hepatitis A vaccine as control. A complex protocol of data and specimen collection was applied, including an interview, pelvic exam for sexually active women, blood for serology and cell-mediated immunity, cervical secretions for local immunity and cells for HPV, Chlamydia trachomatis and Gonorrhea testing. Eighty percent of the women received 3 doses, 12.4% two doses and 7.4% one dose. At visits, compliance with data and specimen collection was close to 100%. Baseline characteristics and age-specific prevalence of HPV and cervical neoplasia are reported. Overall prevalence of HPV was high (50%), with 8.3% of women having HPV 16 and 3.2% HPV 18. LSIL was detected in 12.7% of women at baseline and HSIL in 1.9%. Prevalence of Chlamydia was 14.2%. There was very good agreement in HPV detection between clinician-collected and self-collected specimens (89.4% agreement for all types, kappa 0.59). Follow up will continue with yearly or more frequent examinations for at least 4 years for each participant. PMID:18640170

  20. Vaccines against malaria.

    Science.gov (United States)

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin G on injection site adverse events following anthrax vaccine adsorbed (AVA) in the CDC AVA human clinical trial.

    Science.gov (United States)

    Pondo, Tracy; Rose, Charles E; Martin, Stacey W; Keitel, Wendy A; Keyserling, Harry L; Babcock, Janiine; Parker, Scott; Jacobson, Robert M; Poland, Gregory A; McNeil, Michael M

    2014-06-12

    Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. Published by Elsevier Ltd.

  2. Economic impact of thermostable vaccines.

    Science.gov (United States)

    Lee, Bruce Y; Wedlock, Patrick T; Haidari, Leila A; Elder, Kate; Potet, Julien; Manring, Rachel; Connor, Diana L; Spiker, Marie L; Bonner, Kimberly; Rangarajan, Arjun; Hunyh, Delphine; Brown, Shawn T

    2017-05-25

    While our previous work has shown that replacing existing vaccines with thermostable vaccines can relieve bottlenecks in vaccine supply chains and thus increase vaccine availability, the question remains whether this benefit would outweigh the additional cost of thermostable formulations. Using HERMES simulation models of the vaccine supply chains for the Republic of Benin, the state of Bihar (India), and Niger, we simulated replacing different existing vaccines with thermostable formulations and determined the resulting clinical and economic impact. Costs measured included the costs of vaccines, logistics, and disease outcomes averted. Replacing a particular vaccine with a thermostable version yielded cost savings in many cases even when charging a price premium (two or three times the current vaccine price). For example, replacing the current pentavalent vaccine with a thermostable version without increasing the vaccine price saved from $366 to $10,945 per 100 members of the vaccine's target population. Doubling the vaccine price still resulted in cost savings that ranged from $300 to $10,706, and tripling the vaccine price resulted in cost savings from $234 to $10,468. As another example, a thermostable rotavirus vaccine (RV) at its current (year) price saved between $131 and $1065. Doubling and tripling the thermostable rotavirus price resulted in cost savings ranging from $102 to $936 and $73 to $808, respectively. Switching to thermostable formulations was highly cost-effective or cost-effective in most scenarios explored. Medical cost and productivity savings could outweigh even significant price premiums charged for thermostable formulations of vaccines, providing support for their use. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention.

    Science.gov (United States)

    Jenkins, David

    2008-09-01

    Human papilloma virus (HPV)-16 and -18 are responsible for approximately 70% of invasive cervical cancers worldwide. Other oncogenic HPV types account for almost all the remainder. Importantly, HPV-45 and -31 account for approximately 10%. HPV-18 and -45, along with HPV-16, are found in over 90% of endocervical adenocarcinomas. HPV-45 is the third most frequent HPV type in cervical carcinoma and adenocarcinoma. The AS04-adjuvanted vaccine Cervarix was developed against HPV-16 and -18 focusing on preventing cervical cancer by inducing durable protection against new infection. In clinical trials, it shows evidence of cross-protection against other important oncogenic HPV types using a range of clinicopathological and virological endpoints. The current evidence suggesting the cross-protective effect comes from its overall impact on precancerous lesions and on 12-month or more persistent oncogenic HPV infection, together with specific evidence of protection against incident and new persistent infection lasting 6 months or more with individual HPV types. The use of virological endpoints for such studies is discussed, in particular for cross-protection evaluation, in view of the lower frequency of many important oncogenic HPV types other than HPV-16 or -18 in precancerous lesions and the frequent presence of multiple HPV infections. Both of these factors complicate the interpretation of type-specific, vaccine-induced protection against cervical intraepithelial neoplasia (CIN) lesions, in which other HPV DNA types are found along with HPV-16 and -18. The observed high level of overall protection against clinicopathological lesions, including CIN2+ in the vaccinated subjects (regardless of their HPV DNA status), predicts a potentially broader impact of the vaccine in the prevention of HPV-related precancers that goes beyond HPV-16 and -18. The prevention of persistent infections by individual types such as HPV-45 provides specific information on the protection against that

  4. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  5. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  6. Vaccine Reduces HPV Infections in Young Men

    Science.gov (United States)

    An international randomized clinical trial has shown that the vaccine Gardasil can reduce the incidence of anogenital human papillomavirus (HPV) infections in young men 16 to 26 years of age at the time of vaccination.

  7. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  8. Recent update in HIV vaccine development

    National Research Council Canada - National Science Library

    Shin, So Youn

    2016-01-01

    .... Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV...

  9. 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.

  10. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial.

    Science.gov (United States)

    Davtyan, Hayk; Ghochikyan, Anahit; Petrushina, Irina; Hovakimyan, Armine; Davtyan, Arpine; Poghosyan, Anna; Marleau, Annette M; Movsesyan, Nina; Kiyatkin, Anatoly; Rasool, Suhail; Larsen, Anna Kirstine; Madsen, Peter Juul; Wegener, Karen Malene; Ditlevsen, Dorte Kornerup; Cribbs, David H; Pedersen, Lars Ostergaard; Agadjanyan, Michael G

    2013-03-13

    The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain. However, attempts at targeting the main culprits, neurotoxic Aβ peptides, have thus far proven unsuccessful for improving cognitive function. Recent clinical trials with passively administrated anti-Aβ antibodies failed to slow cognitive decline in mild to moderate AD patients, but suggest that an immunotherapeutic approach could be effective in patients with mild AD. Using an AD mouse model (Tg2576), we tested the immunogenicity (cellular and humoral immune responses) and efficacy (AD-like pathology) of clinical grade Lu AF20513 vaccine. We found that Lu AF20513 induces robust "non-self" T-cell responses and the production of anti-Aβ antibodies that reduce AD-like pathology in the brains of Tg2576 mice without inducing microglial activation and enhancing astrocytosis or cerebral amyloid angiopathy. A single immunization with Lu AF20513 induced strong humoral immunity in mice with preexisting memory T-helper cells. In addition, Lu AF20513 induced strong humoral responses in guinea pigs and monkeys. These data support the translation of Lu AF20513 to the clinical setting with the aims of: (1) inducing therapeutically potent anti-Aβ antibody responses in patients with mild AD, particularly if they have memory T-helper cells generated after immunizations with conventional tetanus toxoid vaccine, and (2) preventing pathological autoreactive T-cell responses.

  11. Are vaccine strain, type or administration protocol risk factors for canine parvovirus vaccine failure?

    Science.gov (United States)

    Altman, K D; Kelman, M; Ward, M P

    2017-10-01

    Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (Pfailure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Alphavirus-Based Vaccines.

    Science.gov (United States)

    Lundstrom, Kenneth

    2016-01-01

    Alphavirus vectors based on Semliki Forest virus, Sindbis virus, and Venezuelan equine encephalitis virus have been widely applied for vaccine development. Naked RNA replicons, recombinant viral particles, and layered DNA vectors have been subjected to immunization in preclinical animal models with antigens for viral targets and tumor antigens. Moreover, a limited number of clinical trials have been conducted in humans. Vaccination with alphavirus vectors has demonstrated efficient immune responses and has showed protection against challenges with lethal doses of virus and tumor cells, respectively. Moreover, vaccines have been developed against alphaviruses causing epidemics such as Chikungunya virus.

  13. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors

    NARCIS (Netherlands)

    Woestenberg, Petra J.; King, Audrey J.; van der Sande, Marianne A B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; Hoebe, Christian J P A; Bogaards, Johannes A.; van Benthem, Birgit H B

    OBJECTIVES: Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11

  14. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial.

    Science.gov (United States)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjærgaard, Jesper; Thøstesen, Lisbeth Marianne; Pihl, Gitte Thybo; Hoffmann, Thomas; Jeppesen, Dorthe Lisbeth; Kofoed, Poul-Erik; Greisen, Gorm; Benn, Christine Stabell; Aaby, Peter; Pryds, Ole; Stensballe, Lone Graff

    2016-05-11

    To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age. Pediatric and maternity wards at three Danish university hospitals. All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. Trial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value BCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications. Trial registration number NCT01694108 at www.clinicaltrials.gov. Copyright © 2016

  15. Vaccination of cattle against tropical theileriosis in Uzbekistan using autochthonous live vaccine.

    Science.gov (United States)

    Rasulov, Ilhan; Fish, L; Shkap, V

    2008-12-19

    In Uzbekistan, 1984 cattle were vaccinated with the TAU-219 autochthonous live Theileria annulata vaccine under field conditions. There were no post-vaccination reactions recorded in calves vaccinated with 10 times the recommended dose, under semi-field conditions. After vaccination 53.9% of the vaccinates developed fever over 39.5 degrees C that lasted for a few days, but none developed clinical theileriosis or required drug treatment during the 3-week follow-up. The numbers of animals in which piroplasms were detected before and after vaccination were similar (7.15% and 7.25%, respectively), indicating previous exposure to T. annulata tick infection. Following vaccination none of the 241 pregnant cows aborted. Milk production during 30-45 days was similar in non-vaccinated and vaccinated cows, at about 5.2-5.9L/day. During 1999-2006 a total of 11,000 field-grazing cattle were safely vaccinated in Uzbekistan.

  16. Diagnostic performance of a rapid in-clinic test for the detection of Canine Parvovirus under different storage conditions and vaccination status.

    Science.gov (United States)

    Kantere, Maria C; Athanasiou, Labrini V; Spyrou, Vassiliki; Kyriakis, Constantinos S; Kontos, Vassilios; Chatzopoulos, Dimitrios C; Tsokana, Constantina N; Billinis, Charalambos

    2015-04-01

    Canine parvovirus (CPV) is one of the most common causes of acute haemorrhagic enteritis in young dogs, while clinical diagnosis is often indecisive. The aim of our study was to evaluate the diagnostic accuracy of an in-clinic rapid test in the detection of CPV infection in dogs. To this end, we compared the Rapid Diagnostic Kit of Canine Parvovirus, Coronavirus and Rotavirus antigen (Quicking(®)) to PCR, which is considered as the most reliable diagnostic method. A total of 78 duplicated faecal samples were collected from diarrhoeic dogs. Vaccination history within a month prior to the onset of diarrhoea was reported for 12 of the sampled dogs. The rapid diagnostic test was performed in 23 of the faecal samples directly, while the rest were placed into a sterile cotton tipped swab suitable for collection and transportation of viruses (Sigma Σ-VCM(®)) and stored at -20 °C. The sensitivity of the Quicking rapid diagnostic test compared to PCR in the total number of samples, in samples from non-vaccinated dogs and in samples tested directly after collection were 22.22% (95% CI: 13.27-33.57%), 26.67% (95% CI: 16.08-39.66%) and 76.47% (95% CI: 50.10-93.04%) respectively, while the specificity of the test was 100% in any case. In conclusion, negative results do not exclude parvoenteritis from the differential diagnosis, especially in dogs with early vaccination history, but a positive result almost certainly indicates CPV infection. An improved sensitivity may be expected when the test is performed immediately. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Vaccines for canine leishmaniasis.

    Science.gov (United States)

    Palatnik-de-Sousa, Clarisa B

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL.

  18. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  19. Vaccines for Canine Leishmaniasis

    Science.gov (United States)

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  20. Vaccine preventable disease incidence as a complement to vaccine efficacy for setting vaccine policy

    Science.gov (United States)

    Gessner, Bradford D.; Feikin, Daniel R.

    2015-01-01

    Traditionally, vaccines have been evaluated in clinical trials that establish vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure important for licensure. Yet, VE does not reflect a vaccine’s public health impact because it does not account for relative disease incidence. An additional measure that more directly establishes a vaccine’s public health value is the vaccine preventable disease incidence (VPDI), which is the incidence of disease preventable by vaccine in a given context. We describe how VE and VPDI can vary, sometimes in inverse directions, across disease outcomes and vaccinated populations. We provide examples of how VPDI can be used to reveal the relative public health impact of vaccines in developing countries, which can be masked by focus on VE alone. We recommend that VPDI be incorporated along with VE into the analytic plans of vaccine trials, as well as decisions by funders, ministries of health, and regulatory authorities. PMID:24731817

  1. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study.

    Science.gov (United States)

    Brekke, Kristin; Sommerfelt, Maja; Ökvist, Mats; Dyrhol-Riise, Anne Margarita; Kvale, Dag

    2017-03-24

    Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41732-744 as well as the effects on pre-existing AB levels to C5/gp41732-744, immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation. Thirty-six HIV patients on effective antiretroviral therapy were randomised to one of three dose levels of Vacc-C5 administered intramuscularly with Alhydrogel or intradermally with GM-CSF as adjuvant through initial immunisation and two booster periods over 26 weeks. Vacc-C5-specific AB were measured by ELISA and T cell responses by both IFN-γ ELISPOT and proliferative assays analysed by flow cytometry. Immune regulation was assessed by functional blockade of the two inhibitory cytokines IL-10 and TGF-β in parallel cultures. Non-parametric statistical tests were applied. Vacc-C5 was found safe and well tolerated in all patients. Only marginal changes in humoral and cellular responses were induced, without any effect on immune activation. Overall, anti-Vacc-C5 AB levels seemed to decrease compared to pre-existing levels. Whereas Vacc-C5-specific CD8+ T cell proliferative responses increased after the first booster period (p = 0.020; CD4+, p = 0.057), they were reduced after the second. In contrast, Vacc-C5-induced T cell regulation increased after completed vaccination (p ≤ 0.027) and was lower at baseline in the few AB responders identified (p = 0.027). The therapeutic HIV vaccine candidate Vacc-C5 safely induced only marginal immune responses

  2. Frederick National Lab Rallies to Meet Demand for Zika Vaccine | FNLCR Staging

    Science.gov (United States)

    The Frederick National Laboratory for Cancer Research’s Vaccine Pilot Plant, part of the Vaccine Clinical Materials Program (VCMP), is helping researchers produce investigational Zika vaccines for a new round of clinical trials. The plant has been

  3. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    Science.gov (United States)

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  4. Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.

    Science.gov (United States)

    Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

    2014-06-01

    Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. © 2013 The Authors. APMIS published by John Wiley & Sons Ltd.

  5. Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial

    Directory of Open Access Journals (Sweden)

    Knutson Keith L

    2010-06-01

    Full Text Available Abstract Background Adjuvant trastuzumab (Herceptin treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2/neu (Her2-specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA (pDNA vaccine in humans. Patients and Methods The vaccine, encoding a full-length signaling-deficient version of the oncogene Her2, was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients treatment was discontinued after one vaccine cycle due to rapid tumor progression or disease-related complications. The primary objective was the evaluation of safety and tolerability of the vaccine regimen. As a secondary objective, treatment-induced Her2-specific immunity was monitored by measuring antibody production as well as T-cell proliferation and cytokine production in response to Her2-derived antigens. Results No clinical manifestations of acute toxicity, autoimmunity or cardiotoxicity were observed after administration of Her2-pDNA in combination with GM-CSF, IL-2 and trastuzumab. No specific T-cell proliferation following in vitro stimulation of freshly isolated PBMC with recombinant human Her2 protein was induced by the vaccination. Immediately after all three cycles of vaccination no or even decreased CD4+ T-cell responses towards Her2-derived peptide epitopes were observed, but a significant increase of MHC class II restricted T-cell responses to Her2 was detected at long term follow-up. Since concurrent trastuzumab therapy was permitted, λ-subclass specific ELISAs were performed to specifically measure endogenous antibody production without interference by trastuzumab. Her2-pDNA vaccination

  6. Oncolytic vaccines.

    Science.gov (United States)

    Elsedawy, Noura B; Russell, Stephen J

    2013-10-01

    Oncolytic viruses are ideal platforms for tumor vaccination because they can mediate the direct in situ killing of tumor cells that release a broad array of tumor antigens and alarmins or danger signals thereby cross-priming antitumor cytotoxic T lymphocytes (CTLs), which mediate the indirect killing of uninfected cells. The balance between the direct and indirect killing phases of oncolytic virotherapy is the key to its success and can be manipulated by incorporating various immunomodulatory genes into the oncolytic virus genome. Recently, the interim analysis of a large multicenter Phase III clinical trial for Talimogene laherparepvec, a granulocyte-macrophage colony stimulating factor-armed oncolytic herpes simplex virus, revealed significant improvement in objective response and durable response rates over control arm and a trend toward improved overall survival. Meanwhile, newer oncolytics are being developed expressing additional immunomodulatory transgenes to further enhance cross-priming and the generation of antitumor CTLs and to block the immunosuppressive actions of the tumor microenvironment. Since oncolytic vaccines can be engineered to kill tumor cells directly, modulate the kinetics of the antitumor immune response and reverse the immunosuppressive actions of the tumor, they are predicted to emerge as the preferred immunotherapeutic anticancer weapons of the future.

  7. Vaccine Finder

    Science.gov (United States)

    ... list . Showing availability for 25,354 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  8. Vaccine Safety

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  9. Rotavirus Vaccine

    Science.gov (United States)

    ... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...

  10. Design and pre-clinical profiling of a Plasmodium falciparum MSP-3 derived component for a multi-valent virosomal malaria vaccine

    Directory of Open Access Journals (Sweden)

    Boato Francesca

    2009-12-01

    Full Text Available Abstract Background Clinical profiling of two components for a synthetic peptide-based virosomal malaria vaccine has yielded promising results, encouraging the search for additional components for inclusion in a final multi-valent vaccine formulation. This report describes the immunological characterization of linear and cyclized synthetic peptides comprising amino acids 211-237 of Plasmodium falciparum merozoite surface protein (MSP-3. Methods These peptides were coupled to phosphatidylethanolamine (PE; the conjugates were intercalated into immunopotentiating reconstituted influenza virosomes (IRIVs and then used for immunizations in mice to evaluate their capacity to elicit P. falciparum cross-reactive antibodies. Results While all MSP-3-derived peptides were able to elicit parasite-binding antibodies, stabilization of turn structures by cyclization had no immune-enhancing effect. Therefore, further pre-clinical profiling was focused on FB-12, a PE conjugate of the linear peptide. Consistent with the immunological results obtained in mice, all FB-12 immunized rabbits tested seroconverted and consistently elicited antibodies that interacted with blood stage parasites. It was observed that a dose of 50 μg was superior to a dose of 10 μg and that influenza pre-existing immunity improved the immunogenicity of FB-12 in rabbits. FB-12 production was successfully up-scaled and the immunogenicity of a vaccine formulation, produced according to the rules of Good Manufacturing Practice (GMP, was tested in mice and rabbits. All animals tested developed parasite-binding antibodies. Comparison of ELISA and IFA titers as well as the characterization of a panel of anti-FB-12 monoclonal antibodies indicated that at least the majority of antibodies specific for the virosomally formulated synthetic peptide were parasite cross-reactive. Conclusion These results reconfirm the suitability of IRIVs as a carrier/adjuvant system for the induction of strong humoral

  11. A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

    Science.gov (United States)

    Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

    2008-08-18

    CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

  12. Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

    OpenAIRE

    Lee, SJ; Newman, PA; Duan, N.; Cunningham, WE

    2014-01-01

    Background: Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability. Methods: HIV vaccine attitude items wer...

  13. Universal influenza vaccines: Shifting to better vaccines.

    Science.gov (United States)

    Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

    2016-06-03

    Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  14. Are licensed canine parvovirus (CPV2 and CPV2b) vaccines able to elicit protection against CPV2c subtype in puppies?: A systematic review of controlled clinical trials.

    Science.gov (United States)

    Hernández-Blanco, Beatriz; Catala-López, Ferrán

    2015-10-22

    Severe gastroenteritis caused by canine parvovirus type 2 (CPV2) is a serious life-threatening disease in puppies less than 4-months of age. The emergence of new variants has provoked some concern about the cross-protection elicited by licensed canine parvovirus modified-live type 2 (CPV2) and type 2b (CPV2b) vaccines against the most recent subtype CPV2c. A systematic review was carried out to assess the efficacy of commercial vaccines. We conducted a literature search of Pub Med/MEDLINE from January 1990 to May 2014. This was supplemented by hand-searching of related citations and searches in Google/Google Scholar. Controlled clinical trials in which vaccinated puppies were challenged with CPV2c virus were evaluated. Reporting of outcome measures and results for vaccine efficacy were critically appraised through a variety of clinical signs, serological tests, virus shedding and the ability to overcome maternally derived antibodies (MDA) titres. Six controlled clinical trials were included in the review. In most cases, the results of the selected studies reported benefits in terms of clinical signs, serological tests and virus shedding. However, MDA interference was not considered or evaluated in 5 of the selected trials. No accurate definitions of baseline healthy status and/or clinical outcomes were provided. Methods of randomization, allocation concealment and blinding were usually poorly reported. As a result of the limited number of included studies matching the inclusion criteria, the small sample sizes, short follow-up and the methodological limitations observed, it was not possible to reach a final conclusion regarding the cross-protection of licensed CPV2 and CPV2b vaccines against the subtype 2c in puppies. Further and specifically designed trials are required in order to elucidate whether cross-protection is acquired from licensed CPV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  16. Rotavirus vaccines.

    Science.gov (United States)

    Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.

    2000-10-01

    The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.

  17. 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....

  18. Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

    Science.gov (United States)

    Munson, Samantha; Raluy-Callado, Mireia; Lambrelli, Dimitra; Wasiak, Radek; Eriksson, Daniel; Gray, Sharon

    2015-08-01

    This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years. © 2015 the Nordic Societies of Public Health.

  19. Distribution of CBP genes in Streptococcus pneumoniae isolates in relation to vaccine types, penicillin susceptibility and clinical site.

    Science.gov (United States)

    Desa, M N; Sekaran, S D; Vadivelu, J; Parasakthi, N

    2008-07-01

    Choline-binding proteins (CBP) have been associated with the pathogenesis of Streptococcus pneumoniae. We screened, using PCR, for the presence of genes (cbpA, D, E, G) encoding these proteins in 34 isolates of pneumococci of known serotypes and penicillin susceptibility from invasive and non-invasive disease. All isolates harboured cbpD and cbpE whereas cbpA and cbpG were found in 47% and 59% respectively; the latter were more frequent in vaccine-associated types and together accounted for 77% of these isolates. No association was observed with penicillin susceptibility but 85% of non-invasive isolates were positive for these genes.

  20. Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media-A Double-Blind Randomized Clinical Trial in Finland.

    Science.gov (United States)

    Vesikari, Timo; Forsten, Aino; Seppä, Ilkka; Kaijalainen, Tarja; Puumalainen, Taneli; Soininen, Anu; Traskine, Magali; Lommel, Patricia; Schoonbroodt, Sonia; Hezareh, Marjan; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2016-09-01

    After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV) to children aged 2-18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media. This trial (ClinicalTrials.gov identifier NCT00839254), nested within a cluster-randomized double-blind invasive pneumococcal disease effectiveness study in Finland (ClinicalTrials.gov identifier NCT00861380), assessed the effectiveness of the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV or PCV10) against bacterial nasopharyngeal carriage and acute otitis media (AOM). Infants (aged 6 weeks to 6 months) received the PHiD-CV or a control vaccine (hepatitis B) (schedule 3+1 or 2+1). Nasopharyngeal swabs were collected at 4 time points post-vaccination from all of the infants and at pre-vaccination from a subset. Parent-reported physician-diagnosed AOM was assessed from first vaccination until last contact (mean follow-up, 18 months). Vaccine effectiveness (VE) was derived as (1 - relative risk)*100, accounting for cluster design in AOM analysis. Significant VE was assessed descriptively (positive lower limit of the non-adjusted 95% confidence interval [CI]). The vaccinated cohort included 5093 infants for carriage assessment and 4117 infants for AOM assessment. Both schedules decreased vaccine-serotype carriage, with a trend toward a lesser effect from the 2+1 schedule ( VE across timpoints 19%-56% [3+1] and 1%-38% [2+1]). Trends toward reduced pneumococcal carriage (predominantly vaccine serotypes 6B, 14, 19F, and 23F), decreased carriage of vaccine-related serotype 19A, and small increases at later time points (ages 14-15 months) in non-vaccine-serotype carriage were observed. No effects on

  1. Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis.

    Science.gov (United States)

    Riveau, Gilles; Deplanque, Dominique; Remoué, Franck; Schacht, Anne-Marie; Vodougnon, Hubert; Capron, Monique; Thiry, Michel; Martial, Joseph; Libersa, Christian; Capron, André

    2012-01-01

    Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) in healthy volunteers, and to determine its immunogenicity. Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum) as adjuvant (n = 8), or Alum alone as a comparator (n = 8), twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8) received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production. Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST. rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical

  2. Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Gilles Riveau

    Full Text Available Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST in healthy volunteers, and to determine its immunogenicity.Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum as adjuvant (n = 8, or Alum alone as a comparator (n = 8, twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8 received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production.Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST.rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that

  3. Vaccines for human papillomavirus infection: a critical analysis.

    Science.gov (United States)

    Nath, Amiya Kumar; Thappa, Devinder Mohan

    2009-01-01

    This article takes a critical look at the pros and cons of human papillomavirus (HPV) vaccines. There is enough evidence to suggest that the prophylactic vaccines are efficacious in preventing various benign and malignant conditions (including cervical cancers) caused by HPV. Even though the vaccine is costly, hypothetical analysis has shown that HPV vaccination will be cost effective in the long run. Therapeutic HPV vaccines used to treat established disease are still undergoing evaluation in clinical studies, and results seem to be encouraging. Although several countries have started mandatory vaccination programs with the prophylactic HPV vaccines, conservatives have voiced concerns regarding the moral impact of such vaccination programs.

  4. Things Are Not as Bad as They Seem: Physicians' Ability to Predict Their Clinical Practice When a New Vaccine Becomes Available

    OpenAIRE

    Seewald, Laura; Hurley, Laura; Crane, Lori A; Dong, Fran; Stokley, Shannon; Matthew F Daley; Barrow, Jennifer; Babbel, Christine; Dickinson, L Miriam; Kempe, Allison

    2013-01-01

    Survey results regarding primary care physicians' likelihood of recommending a new vaccine were compared before and after the vaccine was licensed by the Food and Drug Administration for three new vaccines: herpes zoster (HZ), human papillomavirus (HPV) and rotavirus (RV), using physician networks representative of United States physicians. The main purpose of this study was to determine (a) how accurately physicians predict their eventual vaccine recommendations and the barriers they will ex...

  5. A novel use of a statewide telecolposcopy network for recruitment of participants in a Phase I clinical trial of a human papillomavirus therapeutic vaccine.

    Science.gov (United States)

    Stratton, Shawna L; Spencer, Horace J; Greenfield, William W; Low, Gordon; Hitt, Wilbur C; Quick, Charles M; Jeffus, Susanne K; Blackmon, Victoria; Nakagawa, Mayumi

    2015-06-01

    Historically, recruitment and retention of young women in intervention-based clinical trials have been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single-arm, single-institution, dose-escalation Phase I clinical trial. Women with recent Papanicolaou smear results showing high-grade squamous intraepithelial lesions or results that could not rule out high-grade squamous intraepithelial lesion were eligible to enroll. Patients with biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible. Colposcopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of high-grade squamous intraepithelial lesion was confirmed with biopsy and other inclusion criteria were met. The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. Potential vaccine candidates were recruited through direct advertisement as well as referrals, including referrals through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention, including face-to-face contact with the study coordinator at the time of consent and most of study visits; frequent contact using text messaging, phone calls, and e-mails; and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of

  6. Things are not as bad as they seem: physicians' ability to predict their clinical practice when a new vaccine becomes available.

    Science.gov (United States)

    Seewald, Laura; Hurley, Laura; Crane, Lori A; Dong, Fran; Stokley, Shannon; Daley, Matthew F; Barrow, Jennifer; Babbel, Christine; Dickinson, L Miriam; Kempe, Allison

    2013-05-01

    Survey results regarding primary care physicians' likelihood of recommending a new vaccine were compared before and after the vaccine was licensed by the Food and Drug Administration for three new vaccines: herpes zoster (HZ), human papillomavirus (HPV) and rotavirus (RV), using physician networks representative of United States physicians. The main purpose of this study was to determine (a) how accurately physicians predict their eventual vaccine recommendations and the barriers they will experience in delivering the new vaccine and (b) whether physicians shift towards more or less strongly recommending a new vaccine from pre- to post-licensure. Responses from 284, 152 and 184 physicians were analyzed for the three vaccines, respectively. For all vaccines, there was a significant association between physicians' pre- and post-licensure recommendations (pvaccine more strongly than they had anticipated pre-licensure. Before vaccine availability, physicians tended to predict greater barriers to vaccine delivery than they eventually experienced. Surveys are useful for predicting physician practices, but may provide a slightly pessimistic view of physician adoption of new vaccines. Such data can be helpful in devising strategies to encourage vaccine delivery by physicians. Copyright © 2013 Longwoods Publishing.

  7. Vaccine allergies.

    Science.gov (United States)

    Chung, Eun Hee

    2014-01-01

    Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered.

  8. Is influenza vaccination in asthmatic children helpful?

    Science.gov (United States)

    Bueving, H J

    2006-01-01

    The rationale for influenza vaccination in asthmatic children theoretically lies in prevention of exacerbations and serious complications like pneumonia. Solid evidence from randomized clinical trials of its preventive effects on these clinical endpoints is, however, lacking. Nevertheless, most Western guidelines advise to vaccinate these children. In the real life situation this advice isn't very well followed: vaccine coverage for this indication is low. To assess the usefulness of influenza vaccination in children with asthma a set of fundamental questions regarding this activity is presented and answered. This leads to the conclusion that, given the evidence, influenza vaccination in children with mild to moderate disease should be reconsidered.

  9. A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries.

    Directory of Open Access Journals (Sweden)

    David J Diemert

    2017-01-01

    Full Text Available Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants' understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington

  10. A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries.

    Science.gov (United States)

    Diemert, David J; Lobato, Lucas; Styczynski, Ashley; Zumer, Maria; Soares, Amanda; Gazzinelli, Maria Flávia

    2017-01-01

    Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants' understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington, DC. Although there

  11. Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov

    2018-01-01

    antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit......The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient...... sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKRCCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1...

  12. 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. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. FLU VACCINATION

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  14. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  15. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  16. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  17. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT be ... What is live, attenuated influenza vaccine-LAIV (nasal spray)?A dose of flu vaccine is recommended every flu season. Children younger ...

  18. Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials.

    Directory of Open Access Journals (Sweden)

    Wendy Stevens

    2008-04-01

    Full Text Available An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study.Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia. Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP.Of the 2990 volunteers who were screened, 2387 (80% were enrolled, and 2107 (71% were included in the analysis (52% men, 48% women. Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%, significant medical history (76, 13% and inability to complete the informed consent process (73, 13%. Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38% and antibodies against Hepatitis C (95, 34%. This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all

  19. Universal influenza virus vaccines and therapeutic antibodies.

    Science.gov (United States)

    Nachbagauer, R; Krammer, F

    2017-04-01

    Current influenza virus vaccines are effective when well matched to the circulating strains. Unfortunately, antigenic drift and the high diversity of potential emerging zoonotic and pandemic viruses make it difficult to select the right strains for vaccine production. This problem causes vaccine mismatches, which lead to sharp drops in vaccine effectiveness and long response times to manufacture matched vaccines in case of novel pandemic viruses. To provide an overview of universal influenza virus vaccines and therapeutic antibodies in preclinical and clinical development. PubMed and clinicaltrials.gov were used as sources for this review. Universal influenza virus vaccines that target conserved regions of the influenza virus including the haemagglutinin stalk domain, the ectodomain of the M2 ion channel or the internal matrix and nucleoproteins are in late preclinical and clinical development. These vaccines could confer broad protection against all influenza A and B viruses including drift variants and thereby abolish the need for annual re-formulation and re-administration of influenza virus vaccines. In addition, these novel vaccines would enhance preparedness against emerging influenza virus pandemics. Finally, novel therapeutic antibodies against the same conserved targets are in clinical development and could become valuable tools in the fight against influenza virus infection. Both universal influenza virus vaccines and therapeutic antibodies are potential future options for the control of human influenza infections. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. Vaccine Therapy for Unresectable Chordoma

    Science.gov (United States)

    In this phase II clinical trial, adult patients with inoperable chordoma who are scheduled to undergo radiation therapy will be randomly assigned to receive a yeast-based vaccine that targets a protein called brachyury or a placebo injection.

  1. Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine.

    Science.gov (United States)

    Breiman, Robert F; Zaman, K; Armah, George; Sow, Samba O; Anh, Dang Duc; Victor, John C; Hille, Darcy; Ciarlet, Max; Neuzil, Kathleen M

    2012-04-27

    Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score≥11, severe; score≥15, very severe). Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score≥11), and very severe (score≥15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained

  2. Rotavirus vaccines in routine use.

    Science.gov (United States)

    Tate, Jacqueline E; Parashar, Umesh D

    2014-11-01

    Vaccines are now available to combat rotavirus, the most common cause of severe diarrhea among children worldwide. We review clinical trial data for available rotavirus vaccines and summarize postlicensure data on effectiveness, impact, and safety from countries routinely using these vaccines in national programs. In these countries, rotavirus vaccines have reduced all-cause diarrhea and rotavirus hospitalizations by 17%-55% and 49%-92%, respectively, and all-cause diarrhea deaths by 22%-50% in some settings. Indirect protection of children who are age-ineligible for rotavirus vaccine has also been observed in some high and upper middle income countries. Experience with routine use of rotavirus vaccines in lower middle income countries has been limited to date, but vaccine introductions in such countries have been increasing in recent years. The risk-benefit analysis of rotavirus vaccines is extremely favorable but other strategies to improve the effectiveness of the vaccine, particularly in lower middle income settings, should be considered. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Heterologous vaccine effects

    NARCIS (Netherlands)

    Saadatian-Elahi, M.; Aaby, P.; Shann, F.; Netea, M.G.; Levy, O.; Louis, J.; Picot, V.; Greenberg, M.; Warren, W.

    2016-01-01

    The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological

  4. Intradermal vaccination for infants and children.

    Science.gov (United States)

    Saitoh, Akihiko; Aizawa, Yuta

    2016-09-01

    Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children.

  5. Microneedle and mucosal delivery of influenza vaccines

    Science.gov (United States)

    Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

    2017-01-01

    In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

  6. [Acute intestinal infections: current and upcoming vaccines].

    Science.gov (United States)

    Erlich, Paul; Sansonetti, Philippe J

    2013-01-01

    Currently, only a few licensed vaccines against intestinal infections are available. Existing vaccines have shown good efficacy when used by travelers in industrialized countries. However, these vaccines have lower efficacy in endemic areas with high prevalence of enteric pathogens. Current vaccines are too expensive to be efficiently distributed in endemic countries. Immune correlates of protection are not well defined for current licensed vaccines. A better understanding of protection mechanisms at the intestinal mucosal surfaces should allow the development of more efficient vaccines. Gut physiology and microbial composition play an important role in both physical integrity and immunological status of the gastro-intestinal tract. These parameters can partially explain the disparities observed in current vaccines efficiency. Several next-generation vaccines combined or not with adjuvant able to promote a strong mucosal response in the intestine, are under preclinical and clinical investigations. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  7. Vaccination of healthcare workers: A review

    Science.gov (United States)

    Haviari, Skerdi; Bénet, Thomas; Saadatian-Elahi, Mitra; André, Philippe; Loulergue, Pierre; Vanhems, Philippe

    2015-01-01

    Vaccine-preventable diseases are a significant cause of morbidity and mortality. As new vaccines are proving to be effective and as the incidence of some infections decreases, vaccination practices are changing. Healthcare workers (HCWs) are particularly exposed to and play a role in nosocomial transmission, which makes them an important target group for vaccination. Most vaccine-preventable diseases still carry a significant risk of resurgence and have caused outbreaks in recent years. While many professional societies favor vaccination of HCWs as well as the general population, recommendations differ from country to country. In turn, vaccination coverage varies widely for each microorganism and for each country, making hospitals and clinics vulnerable to outbreaks. Vaccine mandates and non-mandatory strategies are the subject of ongoing research and controversies. Optimal approaches to increase coverage and turn the healthcare workforce into an efficient barrier against infectious diseases are still being debated. PMID:26291642

  8. Evolution of Salmonella Typhi outer membrane protein-specific T and B cell responses in humans following oral Ty21a vaccination: A randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Carreño

    Full Text Available Vaccination against complex pathogens such as typhoidal and non-typhoidal Salmonella requires the concerted action of different immune effector mechanisms. Outer membrane proteins (Omps of Salmonella Typhi are potent immunogens, which elicit long-lasting and protective immunity. Here, we followed the evolution of S. Typhi OmpC and F-specific T and B cell responses in healthy volunteers after vaccination with the vaccine strain Ty21a. To follow humoral and cellular immune responses, pre- and post-vaccination samples (PBMC, serum and stool collected from 15 vaccinated and 5 non-vaccinated individuals. Immunoglobulin levels were assessed in peripheral blood by enzyme-linked immunosorbent assay. B cell and T cell activation were analyzed by flow cytometry. We observed a significant increase of circulating antibody-secreting cells and maximal Omp-specific serum IgG titers at day 25 post vaccination, while IgA titers in stool peaked at day 60. Likewise, Omp-specific CD4+ T cells in peripheral blood showed the highest expansion at day 60 post vaccination, concomitant with a significant increase in IFN-γ and TNFα production. These results indicate that S. Typhi Omp-specific B cell responses and polyfunctional CD4+ T cell responses evolve over a period of at least two months after application of the live attenuated vaccine. Moreover, these findings underscore the potential of S. Typhi Omps as subunit vaccine components.ISRCTN18360696.

  9. Vaccination of active component US military personnel against Salmonella Typhi.

    Science.gov (United States)

    Porter, Chad K; Sorrell, Tia; Mitra, Indrani; Riddle, Mark S

    2017-03-27

    Vaccination against Salmonella Typhi is one of the leading public health interventions reducing the risk of typhoid fever. There are two available licensed vaccines, Vivotif, oral live-attenuated, and Typhim Vi, intramuscular Vi capsular polysaccharide. The US military is a high risk travel population commonly vaccinated for S. Typhi. We describe the use of S. Typhi vaccination in this population and the acute reactogenicity profile of these vaccines. Data were obtained from the Defense Medical Surveillance System and vaccination identified between 1998 and 2011 from vaccination codes. Clinical outcomes were assessed for four weeks post vaccination. Adverse event rates and odds ratios were estimated across the two vaccine types. A total of 1.9million predominately male military personnel received 3.6 million S. Typhi vaccinations with 94.3% of vaccinees receiving the Vi capsule vaccine though variability in the vaccine administered was observed. Receipt of other vaccinations in the 6months surrounding the S. Typhi vaccine was common. Rates of nausea (195 per 100,000 vaccinations), headache (13 per 100,000 vaccinations) and fever (40 per 100,000 vaccinations) were significantly higher following Vi capsule vaccination compared to receipt of Vivotif (130, 2, 10 per 100,000 vaccinations, respectively). In contrast the rates of rash and non-infectious diarrhea (186 and 426 per 100,000 vaccinations, respectively) were increased in those receiving Vivotif compared to the Vi capsule vaccine. The US military is a major consumer of S. Typhi vaccines. The parenterally administered vaccine appears to be more amenable, though we were limited in our ability to assess the reasons for its higher usage. While we observed a higher rate of several adverse events in subjects receiving the intramuscular vaccination, the overall rate of these events was low. Future studies assessing more long-term health outcomes are warranted. Published by Elsevier Ltd.

  10. Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

    Science.gov (United States)

    Farizo, Karen M.; And Others

    1990-01-01

    Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

  11. Cancer Vaccines

    Science.gov (United States)

    ... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...

  12. HPV vaccination series completion and co-vaccination: Pairing vaccines may matter for adolescents.

    Science.gov (United States)

    Keim-Malpass, Jessica; McKim Mitchell, Emma; Camacho, Fabian

    2015-10-26

    Very little is known about the effect of concurrent co-vaccination on HPV series completion. This study utilized a retrospective review of a Clinical Data Repository to assess whether concurrent vaccination had an impact on HPV vaccination series completion, and whether there were differences based on age. 3371 patients who received the HPV vaccine at a single academic medical center between the years 2009-2013 were included in this analysis. The adjusted odds ratio (aOR) for effect of concurrent vaccination on series completion for the age group 9-18 was 1.32 (95% CI 1.09, 1.60). Although not statistically significant, the aOR for effect of concurrent vaccination on completion changed direction for the 19-25 age group and was 0.44 (95% CI 0.17, 1.12). This study provides preliminary evidence that pairing the HPV vaccine with one or more co-vaccines may yield a higher HPV vaccination completion rate among adolescents age 9-18. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Vaccines for Malaria: How Close Are We?

    Science.gov (United States)

    Thera, Mahamadou A.; Plowe, Christopher V.

    2012-01-01

    Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants. PMID:22077719

  14. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  15. Vaccines to prevent leishmaniasis.

    Science.gov (United States)

    Kumar, Rajiv; Engwerda, Christian

    2014-03-01

    Leishmaniasis is a parasitic disease that encompasses a range of clinical manifestations affecting people in tropical and subtropical regions of the world. Epidemiological and experimental data indicate that protection from disease can be achieved in most people. In addition, we know how the host immune system must respond to infection in order to control parasite growth. However, there is still no vaccine for use in humans. Here, we review our understanding of host immunity following Leishmania infection and also discuss recent advances in the development of vaccines to prevent leishmaniasis, highlighting a new promising approach that targets the parasite hemoglobin receptor.

  16. [History of vaccination: from empiricism towards recombinant vaccines].

    Science.gov (United States)

    Guérin, N

    2007-01-01

    Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

  17. The march toward malaria vaccines.

    Science.gov (United States)

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  18. 17DD yellow fever vaccine

    Science.gov (United States)

    Martins, Reinaldo M.; Maia, Maria de Lourdes S.; Farias, Roberto Henrique G.; Camacho, Luiz Antonio B.; Freire, Marcos S.; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C.; Lima, Sheila Maria B.; Nogueira, Rita Maria R.; Sá, Gloria Regina S.; Hokama, Darcy A.; de Carvalho, Ricardo; Freire, Ricardo Aguiar V.; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-01-01

    Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. International Register ISRCTN 38082350. PMID:23364472

  19. HIV vaccine strategies.

    Science.gov (United States)

    Nabel, Gary J

    2002-05-06

    Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain cases, such as in HIV infection, where the immune system rarely confers protective immunity. However, there are alternative strategies and areas of research that may facilitate the development of highly effective vaccines. These include the identification of immunogens that elicit broadly neutralizing antibodies, determination of the molecular and cellular basis for immune responses to the components of the infectious agent, the identification of relevant forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function. Answering these basic research questions will aid in rational vaccine design. It is also extremely important to optimize techniques for the testing and production of new vaccines including the quantitation of immune responses in animals and in humans, identification of surrogate markers of immune protection, streamlined vaccine production, and rapid evaluation of candidate vaccines for testing in clinical trials. We have put these ideas into practice in two recent studies in which we generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust humoral responses, to wild-type viral proteins by immunizing mice with genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of plasmid DNA expression vectors.

  20. Mild measles and secondary vaccine failure during a sustained outbreak in a highly vaccinated population.

    Science.gov (United States)

    Edmonson, M B; Addiss, D G; McPherson, J T; Berg, J L; Circo, S R; Davis, J P

    1990-05-09

    A prolonged school-based outbreak of measles provided an opportunity to study "vaccine-modified" mild measles and secondary vaccine failure. Thirty-six (97%) of 37 unvaccinated patients had rash illnesses that met the Centers for Disease Control clinical case definition of measles, but 29 (15%) of 198 vaccinated patients did not, primarily because of low-grade or absent fever. Of 122 patients with seroconfirmed measles, 10 patients (all previously vaccinated) had no detectable measles-specific IgM and significantly milder illness than either vaccinated or unvaccinated patients with IgM-positive serum. Of 108 vaccinated patients with seroconfirmed measles, 17 patients (16%) had IgM-negative serology or rash illnesses that failed to meet the clinical case definition; their mean age (13 years), age at the time of vaccination, and time since vaccination did not differ from those of other vaccinated patients. The occurrence of secondary vaccine failure and vaccine-modified measles does not appear to be a major impediment to measles control in the United States but may lead to underreporting of measles cases and result in overestimation of vaccine efficacy in highly vaccinated populations.

  1. The effect of selenium on immunogenicity of influenza vaccine in the elderly: A case-control double-blinded clinical trial

    Directory of Open Access Journals (Sweden)

    Alireza Janbakhsh

    2016-06-01

    Full Text Available Introduction: Influenza can cause more severe diseases and higher rate of morbidity and mortality in the elderly population. Therefore, they should receive influenza vaccine annually. However, the host response to vaccine is less in older individuals. On the other hand, selenium can act as a stimulator of the immune system and cause increased immunity and response to vaccine. This study was carried out to determine the effect of selenium on antibody production against influenza vaccine. By verifying this effect, selenium can be recommended as an adjuvant therapy in the elderly. Methods: A total of 110 subjects were selected at Infectious Diseases Research Center of Imam Reza Hospital in Kermanshah. They were divided into two groups of adjuvant (N=56 and placebo (N=54. The adjuvant group received influenza vaccine and selenium tablet. The placebo group received influenza vaccine and placebo tablet. Venous blood samples were taken before and four weeks after vaccination and the results were compared between the two groups. Results: Seroconversion, seroprotection, and geometric mean titer (GMT for three strains (H1N1, H3N2, and B were assessed. The seroconversion and GMT rates against influenza B vaccine component were significantly higher in adjuvant group than placebo group. Conclusion: Considering the ability of selenium in induction of a better response to influenza vaccine in older people as well as its low cost and accessibility, selenium can be used to increase antibody level in such cases.

  2. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer.

    Science.gov (United States)

    Lilleby, Wolfgang; Gaudernack, Gustav; Brunsvig, Paal F; Vlatkovic, Ljiljana; Schulz, Melanie; Mills, Kate; Hole, Knut Håkon; Inderberg, Else Marit

    2017-07-01

    In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected lymph nodes. Three dose levels of UV1 were given as intradermal injections combined with GM-CSF (Leukine®). Twenty-one patients in the intention-to-treat population (95%) received conformal radiotherapy. Adverse events reported were predominantly grade 1, most frequently injection site pruritus (86.4%). Serious adverse events considered possibly related to UV1 and/or GM-CSF included anaphylactic reaction in two patients and thrombocytopenia in one patient. Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease. Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.

  3. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

    2011-01-01

    Herpes zoster (HZ) and post-herpetic neuralgia (PHN) are frequently occurring diseases in elderly and in immuno-compromised persons. The live attenuated HZ vaccine boosts an existing immune response, so that the already established varicella-zoster virus infection is kept latent. Vaccination has...... been shown to halve the risk of HZ, and the risk of PHN is reduced by two thirds in people = 60 years. The vaccine is approved for persons aged = 50 years. However, the clinical efficacy of the vaccine is best studied in people aged = 60 years. The vaccine has so far not shown any serious side-effects....

  4. [Human papillomavirus prophylactic vaccine].

    Science.gov (United States)

    Kawana, Kei

    2012-06-01

    Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.

  5. Adolescent Male Human Papillomavirus Vaccination

    Directory of Open Access Journals (Sweden)

    Vivian C. Nanagas MD, MSc

    2016-04-01

    Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.

  6. Effective influenza vaccines for children

    Science.gov (United States)

    Banzhoff, Angelika; Stoddard, Jeffrey J.

    2012-01-01

    Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence.   Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501

  7. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... patterns that increase activation of the innate immune system. Importantly, viral-vectored vaccines that act through the induction of one or more of these factors also may benefit from cytokine coadministration and increased antigen presentation. In order to increase immunogenicity to the level achieved...

  8. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... Educators Search English Español Your Child's Immunizations: Meningococcal Vaccines KidsHealth / For Parents / Your Child's Immunizations: Meningococcal Vaccines Print The meningococcal vaccines protect ...

  9. Advances Towards Painless Vaccination and Newer Modes of Vaccine Delivery.

    Science.gov (United States)

    Garg, Neha; Aggarwal, Anju

    2017-06-16

    Vaccines have been successful in reducing the mortality and morbidity, but most of them are delivered by intramuscular or intravenous route. They are associated with pain to the baby and bring lot of anxiety for the parents. There has been a marked increase in the number of injections required in first two years of life for completing the vaccination schedule. Hence, there is a need to have a painless vaccine delivery system. Numerous new routes of vaccination like, oral, nasal and transdermal routes are being tried. Oral polio and intranasal influenza have already been a success. Other newer approaches like edible vaccines, nasal sprays, dry powder preparations, jet injectors, microneedles and nanopatches are promising in delivering painless vaccines. Many of them are under clinical trials. These vaccine delivery systems will not only be painless but also cost effective, safe and easy to administer in mass population. They may be devoid of the need of cold chain. Painless delivery system will ensure better compliance to vaccination schedule.

  10. Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

    Science.gov (United States)

    Quenee, Lauriane E.; Ciletti, Nancy A.; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

    2012-01-01

    Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing. PMID:21763383

  11. Duration of protective immunity after a single vaccination with a live attenuated bivalent bluetongue vaccine.

    Science.gov (United States)

    Zhugunissov, Kuandyk; Yershebulov, Zakir; Barakbayev, Kainar; Bulatov, Yerbol; Taranov, Dmitriy; Amanova, Zhanat; Abduraimov, Yergali

    2015-12-01

    The prevention of bluetongue is typically achieved with mono- or polyvalent modified- live-attenuated virus (MLV) vaccines. MLV vaccines typically elicit a strong antibody response that correlates directly with their ability to replicate in the vaccinated animal. They are inexpensive, stimulate protective immunity after a single inoculation, and have been proven effective in preventing clinical bluetongue disease. In this study, we evaluated the safety, immunogenicity, and efficacy of a bluetongue vaccine against Bluetongue virus serotypes 4 and 16 in sheep. All the animals remained clinically healthy during the observation period. The vaccinated animals showed no clinical signs except fever (>40.8 °C) for 2-4 days. Rapid seroconversion was observed in the sheep, with the accumulation of high antibody titers in the vaccinated animals. No animal became ill after the challenge, indicating that effective protection was achieved. Therefore, this vaccine, prepared from attenuated bluetongue virus strains, is safe, immunogenic, and efficacious.

  12. Economics of vaccines revisited.

    Science.gov (United States)

    Postma, Maarten J; Standaert, Baudouin A

    2013-05-01

    Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model; (1) appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment; (2) the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries; (3) and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison. (4.)

  13. HIV-1 vaccines

    Science.gov (United States)

    Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

    2014-01-01

    The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

  14. Nursing case management, peer coaching, and hepatitis a and B vaccine completion among homeless men recently released on parole: randomized clinical trial.

    Science.gov (United States)

    Nyamathi, Adeline; Salem, Benissa E; Zhang, Sheldon; Farabee, David; Hall, Betsy; Khalilifard, Farinaz; Leake, Barbara

    2015-01-01

    Although hepatitis A virus (HAV) and hepatitis B virus (HBV) infections are vaccine-preventable diseases, few homeless parolees coming out of prisons and jails have received the hepatitis A and B vaccination series. The study focused on completion of the HAV and HBV vaccine series among homeless men on parole. The efficacy of three levels of peer coaching (PC) and nurse-delivered interventions was compared at 12-month follow-up: (a) intensive peer coaching and nurse case management (PC-NCM); (b) intensive PC intervention condition, with minimal nurse involvement; and (c) usual care (UC) intervention condition, which included minimal PC and nurse involvement. Furthermore, we assessed predictors of vaccine completion among this targeted sample. A randomized control trial was conducted with 600 recently paroled men to assess the impact of the three intervention conditions (PC-NCM vs. PC vs. UC) on reducing drug use and recidivism; of these, 345 seronegative, vaccine-eligible subjects were included in this analysis of completion of the Twinrix HAV/HBV vaccine. Logistic regression was added to assess predictors of completion of the HAV/HBV vaccine series and chi-square analysis to compare completion rates across the three levels of intervention. Vaccine completion rate for the intervention conditions were 75.4% (PC-NCM), 71.8% (PC), and 71.9% (UC; p = .78). Predictors of vaccine noncompletion included being Asian and Pacific Islander, experiencing high levels of hostility, positive social support, reporting a history of injection drug use, being released early from California prisons, and being admitted for psychiatric illness. Predictors of vaccine series completion included reporting having six or more friends, recent cocaine use, and staying in drug treatment for at least 90 days. Findings allow greater understanding of factors affecting vaccination completion in order to design more effective programs among the high-risk population of men recently released from

  15. Risk in vaccine research and development quantified.

    Directory of Open Access Journals (Sweden)

    Esther S Pronker

    Full Text Available To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates have been published for new chemical entities (NCE, little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines.

  16. Status of vaccine research and development of vaccines for malaria.

    Science.gov (United States)

    Birkett, Ashley J

    2016-06-03

    Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  17. Effects of Bacillus Calmette-Guerin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial

    NARCIS (Netherlands)

    Birk, N.M.; Nissen, T.N.; Kjaergaard, J.; Hartling, H.J.; Thostesen, L.M.; Kofoed, P.E.; Stensballe, L.G.; Andersen, A.; Pryds, O.; Netea, M.G.; Benn, C.S.; Nielsen, S.D.; Jeppesen, D.L.

    2017-01-01

    The Bacillus Calmette-Guerin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets,

  18. A Real-Time PCR Assay to Identify and Discriminate Among Wild-Type and Vaccine Strains of Varicella-Zoster Virus and Herpes Simplex Virus in Clinical Specimens, and Comparison With the Clinical Diagnoses

    Science.gov (United States)

    Harbecke, Ruth; Oxman, Michael N.; Arnold, Beth A.; Ip, Charlotte; Johnson, Gary R.; Levin, Myron J.; Gelb, Lawrence D.; Schmader, Kenneth E.; Straus, Stephen E.; Wang, Hui; Wright, Peter F.; Pachucki, Constance T.; Gershon, Anne A.; Arbeit, Robert D.; Davis, Larry E.; Simberkoff, Michael S.; Weinberg, Adriana; Williams, Heather M.; Cheney, Carol; Petrukhin, Luba; Abraham, Katalin G.; Shaw, Alan; Manoff, Susan; Antonello, Joseph M.; Green, Tina; Wang, Yue; Tan, Charles; Keller, Paul M.

    2014-01-01

    A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human β-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID:19475609

  19. Estimating and comparing the clinical and economic impact of paediatric rotavirus vaccination in Turkey using a simple versus an advanced model.

    Science.gov (United States)

    Bakir, Mustafa; Standaert, Baudouin; Turel, Ozden; Bilge, Zeynep Ece; Postma, Maarten

    2013-01-30

    The burden of rotavirus disease is high in Turkey, reflecting the large birth cohort (>1.2 million) and the risk of disease. Modelling can help to assess the potential economic impact of vaccination. We compared the output of an advanced model with a simple model requiring fewer data inputs. If the results are similar, this could be helpful for countries that have few data available. The advanced model was a previously published static Markov cohort model comparing costs and quality-adjusted life-year (QALY) outcomes of vaccination versus no vaccination. In contrast, the simple model used only a decision tree. Both models included data on demography, epidemiology, vaccine efficacy, resource use, unit costs, and utility scores from national databases and published papers. Only the perspective of the health care payer was considered in the analysis. The simple model had 23 variables, compared with 103 in the advanced model to allow additional comparisons of different vaccine types, dose schemes and vaccine waning. With the same input data, both models showed that rotavirus vaccination in Turkey would improve health outcomes (fewer QALYs lost to rotavirus disease). The projected annual cost offsets were $29.9 million in the simple and $29.4 million in the advanced model. Sensitivity analysis indicated that in both models the main cost driver was disease incidence followed by cost for hospital care and medical visits. Vaccine efficacy had a smaller effect. Both models reached similar conclusions. Both projected that rotavirus vaccination in Turkey would improve health outcomes and may result in savings in direct healthcare costs to offset the cost of vaccination. The analysis indicated that the simple model can produce meaningful economic results in conditions where few data are available. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Flu Vaccine Safety Information

    Science.gov (United States)

    ... Types Seasonal Avian Swine/Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) Español ... of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. Hundreds ...

  1. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Avian Swine/Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend on ... or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose vials ...

  2. Vaccine Basics (Smallpox)

    Science.gov (United States)

    ... Side Effects of Vaccination Who Should Get a Smallpox Vaccination? Bioterrorism The Threat Preparedness Detection and Response Bioterrorism ... Revaccinees Examples of Major or “Take” Reactions to Smallpox Vaccination Vaccine Adverse Reaction Images Laboratory Personnel Specimen Collection ...

  3. Your child's first vaccines

    Science.gov (United States)

    ... multi.html . CDC review information for Multi Pediatric Vaccines: Your Child's First Vaccines: What you need to know (VIS): ... of that vaccine. Tell the person giving the vaccines if your child has ever had a severe reaction after any ...

  4. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  5. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine