Elisabeth A Innes
Full Text Available Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.
Ferreira, T B; Alves, P M; Aunins, J G; Carrondo, M J T
Vaccines are the most effective and inexpensive prophylactic tool in veterinary medicine. Ideally, vaccines should induce a lifelong protective immunity against the target pathogen while not causing clinical or pathological signs of diseases in the vaccinated animals. However, such ideal vaccines are rare in the veterinary field. Many vaccines are either of limited effectiveness or have harmful side effects. In addition, there are still severe diseases with no effective vaccines. A very important criterion for an ideal vaccine in veterinary medicine is low cost; this is especially important in developing countries and even more so for poultry vaccination, where vaccines must sell for a few cents a dose. Traditional approaches include inactivated vaccines, attenuated live vaccines and subunit vaccines. Recently, genetic engineering has been applied to design new, improved vaccines. Adenovirus vectors are highly efficient for gene transfer in a broad spectrum of cell types and species. Moreover, adenoviruses often induce humoral, mucosal and cellular immune responses to antigens encoded by the inserted foreign genes. Thus, adenoviruses have become a vector of choice for delivery and expression of foreign proteins for vaccination. Consequently, the market requirements for adenovirus vaccines are increasing, creating a need for production methodologies of concentrated vectors with warranted purity and efficacy. This review summarizes recent developments and approaches of adenovirus production and purification as the application of these vectors, including successes and failures in clinical applications to date.
Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.
Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009
Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.
The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host
Embregts, Carmen W E; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines for mass vaccination of farmed fish species. Furthermore, using various examples from the human and veterinary vaccine development, we propose additional approaches to fish vaccine design also considering recent advances in fish mucosal immunology and novel molecular tools. Finally, we discuss the pros and cons of using the zebrafish as a pre-screening animal model to potentially speed up vaccine design and testing for aquaculture fish species. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bulkhanov, R.U.; Butaev, M.K.; Mirsaev, B.Sh.; Ryasnaynskiy, I.V.; Yuldashev, R.Yu.
Full text: In applied radiology scientists usually use stimulating, mutagenic and inactivating effects of gamma-radiation. In this report there are the results of gamma-radiation inactivating effect for radiovaccine making biotechnology development for veterinary. Inactivation with hamma-irradiation gives us opportunity to make highly immunogenic vaccines, which cause minimum damage of antigenic contaminants structure. With the help of radiative biotechnology we can produce highly effective monoassociated and polyvalented radiovaccines against the most wide-spread infections disease in agricultural animals, young animals in particular (calves, lambs, sucking-pigs). These diseases include such infection diseases as colibacterioses, salmonellosis, pasterellosis, which cause much economic damage to stockbreeding i.e. loss of cattle, slow growth of young animal, lack of offsprings, decrease of reproduction properties. Monovaccines are used for these disease prophylaxis as well as associated and polyvalented vaccines. Taking into consideration the necessity of vaccine improvement and great amount of associated vaccines, one of the main problems of veterinary is the development of vaccines of new generation, which can induce immunity against several diseases in agricultural animals. That is why, radiative biotechnology of radiovaccines creation was developed and is used in radiative laboratory of Uzbek Scientific Veterinary Institute (Bulkhanov R.U., 1999, 2001), A ssociated radiovaccine against colibacteriosis, salmonellosis of calves, kids , 'Associated radiovaccine against colibacteriosis and salmonellosis of calves', 'Polyvalented radiovaccine against pasterellosis, salmonellosis and colibacteriosis in agricultural animals' were developed with the help of radiative biotechnology and are successfully used in veterinary practice. The advantage of these radiovaccines is that they produce one year immunity and you need twice less dosage and revaccinations. More than
Audonnet, J Ch; Lechenet, J; Verschuere, B
Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.
... and Veterinary Rabies Vaccine Testing: State of the Science and Planning the Way Forward AGENCY... (NICEATM) announces an ``International Workshop on Alternative Methods for Human and Veterinary Rabies... rabies vaccine potency testing, and to develop an implementation strategy to achieve global acceptance...
Pencheva, Daniela; Genova-Kalou, Petia; Bryaskova, Rayna
Experimental and laboratory tests were carried out in order to identify the advantages of “ghost” antigens obtained by treatment of the bacterial cell with silver nanoparticles in comparison to the inactivated antigens obtained by classical methods as heating or treatment with formalin. The Minimal Bactericidal Concentrations (MBC) of the hybrid material containing silver nanoparticles (PVA/AgNps), used for inactivation of the tested E. coli strains were determined and they were categorized as susceptible to the action of silver nanoparticles. The changes in the structure of the bacterial cells obtained after the treatment with the hybrid material containing silver nanoparticles or with formaldehyde, respectively, were established by TEM (Transmission electron microscopy) analysis. The advantages of the “ghost” vaccines are expressed in undamaged cell wall and better immunogenicity, thus resulting in faster formation of specific titer after immunization of experimental animals. Key words: E. coli O149, E. coli O157H7, “ghost” vaccine, silver nanoparticles, TEM
Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna
Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.
Ramezanpour, Bahar; Foucauld, de Jean; Kortekaas, Jeroen
On the 9th of November 2015, preceding the World Veterinary Vaccine Congress, a workshop was held to discuss how veterinary vaccines can be deployed more rapidly to appropriately respond to future epizootics in Europe. Considering their potential and unprecedented suitability for surge
Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers
Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.
Pastoret, P P
Veterinary vaccinology is a very interesting and rapidly developing field. In fact veterinary vaccines are not only used for the prevention of infectious diseases in the animal health sector, but also help to solve problems of public health, to reduce detrimental environmental impact of the use of some veterinary drugs and prevent the emergence of resistance of micro-organisms or parasites. After a short introduction, this paper will deal with the use of vaccines for animal health and welfare, including new developments in the veterinary field such as marker vaccines and vectored vaccines, the special case of equine influenza-inactivated vaccines and the use of veterinary vaccines in public health. The conclusions will analyse the reasons as to why develop veterinary vaccines and the obstacles to their development.
Jacob, Siju S; Cherian, Susan; Sumithra, T G; Raina, O K; Sankar, M
Protection of domestic animals against parasitic infections remains a major challenge in most of the developing countries, especially in the surge of drug resistant strains. In this circumstance vaccination seems to be the sole practical strategy to combat parasites. Most of the presently available live or killed parasitic vaccines possess many disadvantages. Thus, expression of parasitic antigens has seen a continued interest over the past few decades. However, only a limited success was achieved using bacterial, yeast, insect and mammalian expression systems. This is witnessed by an increasing number of reports on transgenic plant expression of previously reported and new antigens. Oral delivery of plant-made vaccines is particularly attractive due to their exceptional advantages. Moreover, the regulatory burden for veterinary vaccines is less compared to human vaccines. This led to an incredible investment in the field of transgenic plant vaccines for veterinary purpose. Plant based vaccine trials have been conducted to combat various significant parasitic diseases such as fasciolosis, schistosomosis, poultry coccidiosis, porcine cycticercosis and ascariosis. Besides, passive immunization by oral delivery of antibodies expressed in transgenic plants against poultry coccidiosis is an innovative strategy. These trials may pave way to the development of promising edible veterinary vaccines in the near future. As the existing data regarding edible parasitic vaccines are scattered, an attempt has been made to assemble the available literature. Copyright © 2013 Elsevier Ltd. All rights reserved.
Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers
Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...
... Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for Disease..., filed 12/21/2007, entitled ``Development of Rift Valley Fever Virus Utilizing Reverse Genetics,'' US... (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008/ 087023, filed 12/16/2008, entitled...
Mendez, D; Foyle, L; Cobbold, R; Speare, R
To determine the rabies vaccination status of Queensland veterinarians and veterinary students and their perception of zoonotic risk from Australian bat lyssavirus (ABLV). Cross-sectional questionnaire surveys. Questionnaires were sent by post in 2011 to veterinary surgeons registered in Queensland, to final-year veterinary students at James Cook University via SurveyMonkey® in 2013 and to final-year veterinary students at James Cook University and University of Queensland via SurveyMonkey® in 2014. The response rate for registered veterinarians was 33.5% and for veterinary students 33.3% and 30% in 2013 and 2014, respectively. Of the 466 registered veterinary surgeons, 147 (31.5%) had been vaccinated, with 72 (15.5%) currently vaccinated. For veterinary students the rabies vaccination rate was 20.0% (4/20) and 13.0% (6/46) in the 2013 and 2014 surveys, respectively. More than 95% of veterinary students had received the mandatory Q fever vaccine. Both veterinarians and students regarded bats and horses as high-risk species for zoonoses. Queensland veterinarians and veterinary students have low levels of protection against ABLV. Although incidents of ABLV spilling over from a bat to a domestic mammal are likely to remain rare, they pose a significant human health and occupational risk given the outcome of infection in humans is high consequence. Principals of veterinary practices and veterinary authorities in Australia should implement a policy of rabies vaccination for clinical staff and veterinary students. © 2018 Australian Veterinary Association.
... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...
Cave, N J; Jackson, R; Bridges, J P
To determine current practices and attitudes towards vaccination of dogs and cats of veterinarians in New Zealand; the methods used for informing clients on which vaccines to use, and the preferred site for vaccination of cats. A postal questionnaire was sent to all 483 listed veterinary practices in New Zealand during February 2012. Some questions were specific to pet dogs, cats, or working farm dogs. Responses were categorised according to practice type and geographical region of the respondent. Factors associated with respondent recommendation of annual vaccination with modified live viral (MLV) vaccines were examined using logistic regression analysis. Vaccines that were considered to be essential for every animal were defined as core; those that may be recommended for animals whose location or lifestyle placed them at risk, were defined as non-core. There were 204 useable returns, equivalent to a response rate of 42.2%, distributed across the country. Annual vaccination with MLV vaccines of dogs was recommended by 54/198 (27.3%) respondents, and of cats by 107/181 (59.1%) respondents. Factors associated with the recommendation of annual administration of MLV vaccines to dogs included being a companion animal practice, a desire for policies on vaccination to be left to individual clinics, and having one veterinarian in the practice. Administration of the final vaccination for puppies was recommended at ≥14 weeks old by 55/185 (29.7%) respondents, and for kittens at ≥13 weeks old by 42/183 (23%) respondents. Of respondents that administered MLV vaccines annually, 62/103 (60.2%) believed reducing the frequency of vaccination would reduce income, and 52/103 (50.5%) considered it would have a negative effect on animal health. Advice to enable clients to decide which non-core vaccines were administered was given by 181/199 (91%) respondents. Factors considered when recommending a vaccine included consideration of risk to individual patients (190/203; 93
Full Text Available Q fever, caused by Coxiella burnetii, is a serious zoonotic disease in humans with a worldwide distribution. Many species of animals are capable of transmitting C. burnetii, and consequently all veterinary workers are at risk for this disease. An effective Q fever vaccine has been readily available and used in Australia for many years in at-risk groups, and the European Centre for Disease Prevention and Control has recently also called for the use of this vaccine among at-risk groups in Europe. Little is known about attitudes towards this vaccine and vaccine uptake in veterinary workers. This study aimed to determine the Q fever vaccination status of veterinarians and veterinary nurses in Australia and to assess and compare the knowledge and attitudes towards Q fever disease and vaccination of each cohort. An online cross-sectional survey performed in 2014 targeted all veterinarians and veterinary nurses in Australia. Responses from 890 veterinarians and 852 veterinary nurses were obtained. Binary, ordinal and multinomial logistic regression were used to make comparisons between the two cohorts. The results showed that 74% of veterinarians had sought vaccination compared to only 29% of veterinary nurses. Barriers to vaccination among those not vaccinated did not differ between cohorts, and included a lack of perceived risk, financial expense, time constraints, and difficulty in finding a vaccine provider. Poor knowledge and awareness of Q fever disease and vaccination were additional and notable barriers for the veterinary nursing cohort, suggesting veterinary clinics and veterinarians may not be meeting their legal responsibility to educate staff about risks and risk prevention. Further evaluation is needed to identify the drivers behind seeking and recommending vaccination so that recommendations can be made to improve vaccine uptake.
Sellens, Emily; Norris, Jacqueline M.; Dhand, Navneet K.; Heller, Jane; Hayes, Lynne; Gidding, Heather F.; Willaby, Harold; Wood, Nicholas; Bosward, Katrina L.
Q fever, caused by Coxiella burnetii, is a serious zoonotic disease in humans with a worldwide distribution. Many species of animals are capable of transmitting C. burnetii, and consequently all veterinary workers are at risk for this disease. An effective Q fever vaccine has been readily available and used in Australia for many years in at-risk groups, and the European Centre for Disease Prevention and Control has recently also called for the use of this vaccine among at-risk groups in Europe. Little is known about attitudes towards this vaccine and vaccine uptake in veterinary workers. This study aimed to determine the Q fever vaccination status of veterinarians and veterinary nurses in Australia and to assess and compare the knowledge and attitudes towards Q fever disease and vaccination of each cohort. An online cross-sectional survey performed in 2014 targeted all veterinarians and veterinary nurses in Australia. Responses from 890 veterinarians and 852 veterinary nurses were obtained. Binary, ordinal and multinomial logistic regression were used to make comparisons between the two cohorts. The results showed that 74% of veterinarians had sought vaccination compared to only 29% of veterinary nurses. Barriers to vaccination among those not vaccinated did not differ between cohorts, and included a lack of perceived risk, financial expense, time constraints, and difficulty in finding a vaccine provider. Poor knowledge and awareness of Q fever disease and vaccination were additional and notable barriers for the veterinary nursing cohort, suggesting veterinary clinics and veterinarians may not be meeting their legal responsibility to educate staff about risks and risk prevention. Further evaluation is needed to identify the drivers behind seeking and recommending vaccination so that recommendations can be made to improve vaccine uptake. PMID:26756210
MacDonald, Jacqueline; Doshi, Ketan; Dussault, Marike; Hall, J Christopher; Holbrook, Larry; Jones, Ginny; Kaldis, Angelo; Klima, Cassidy L; Macdonald, Phil; McAllister, Tim; McLean, Michael D; Potter, Andrew; Richman, Alex; Shearer, Heather; Yarosh, Oksana; Yoo, Han Sang; Topp, Edward; Menassa, Rima
The production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
Richens, I F; Hobson-West, P; Brennan, M L; Lowton, R; Kaler, J; Wapenaar, W
There is limited research investigating the motivators and barriers to vaccinating dairy cattle. Veterinary surgeons have been identified as important sources of information for farmers making vaccination and disease control decisions, as well as being farmers' preferred vaccine suppliers. Vets' perception of their own role and communication style can be at odds with farmers' reported preferences. The objective of this study was to investigate how dairy farmers perceived the role of vets in implementing vaccination strategies on their farm. Semi-structured interviews were conducted with 24 dairy farmers from across Britain. The data were analysed using thematic analysis. Analysis revealed that farmers perceive vets to have an important role in facilitating decision-making in all aspects of vaccination, including the aspects of vaccine distribution and advice on implementation. This important role is acknowledged by farmers who have regular veterinary contact, but also farmers with solely emergency veterinary contact. Given this finding, future work should investigate the attitudes of vets towards vaccination and how they perceive their role. Combining this knowledge will enable optimisation of vaccination strategies on British dairy farms. British Veterinary Association.
Schiffelers, Marie-Jeanne W. A.; Blaauboer, Bas J.; Bakker, Wieger E.; Hendriksen, Coenraad F. M.
In April 2013 the mouse antibody serum neutralization test (SNT) was formally incorporated into European Pharmacopoeia monograph 0451 for potency testing of inactivated veterinary rabies vaccines. The SNT is designed to replace the highly variable and pain and distress causing NIH mouse rabies
Lithgow, Karen V; Cameron, Caroline E
Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.
Next generation sequencing technology has become widely available and it offers many new opportunities in vaccine technology. Both human and veterinary medicine has numerous examples of adventitious agents being found in live vaccines. In veterinary medicine a continuing trend is the use of viral ...
Community Perceptions on Integrating Animal Vaccination and Health Education by Veterinary and Public Health Workers in the Prevention of Brucellosis among Pastoral Communities of South Western Uganda
Kansiime, Catherine; Atuyambe, Lynn M.; Asiimwe, Benon B.; Mugisha, Anthony; Mugisha, Samuel; Guma, Victor; Rwego, Innocent B.; Rutebemberwa, Elizeus
Background Brucellosis is a zoonotic disease of veterinary, public health, and economic significance in most developing countries, yet there are few studies that show integrated human and veterinary health care intervention focusing on integration at both activity and actors levels. The aim of our study, therefore, was to explore community perceptions on integration of animal vaccination and health education by veterinary and public health workers in the management of brucellosis in Uganda. Methods This study used a qualitative design where six Focus Group Discussions (FGDs) that were homogenous in nature were conducted, two from each sub-county, one with the local leaders, and another with pastoralists and farmers. Five Key Informant Interviews (KIIs) with two public health workers and three veterinary extension workers from three sub-counties in Kiruhura district, Uganda were conducted. All FGDs were conducted in the local language and tape recorded with consent from the participants. KIIs were in English and later transcribed and analyzed using latent content data analysis method. Results All the groups mentioned that they lacked awareness on brucellosis commonly known as Brucella and its vaccination in animals. Respondents perceived improvement in human resources in terms of training and recruiting more health personnel, facilitation of the necessary activities such as sensitization of the communities about brucellosis, and provision of vaccines and diagnostic tests as very important in the integration process in the communities. The FGD participants also believed that community participation was crucial for sustainability and ownership of the integration process. Conclusions The respondents reported limited knowledge of brucellosis and its vaccination in animals. The community members believed that mass animal vaccination in combination with health education about the disease is important and possible if it involves government and all other stakeholders such
Community Perceptions on Integrating Animal Vaccination and Health Education by Veterinary and Public Health Workers in the Prevention of Brucellosis among Pastoral Communities of South Western Uganda.
Full Text Available Brucellosis is a zoonotic disease of veterinary, public health, and economic significance in most developing countries, yet there are few studies that show integrated human and veterinary health care intervention focusing on integration at both activity and actors levels. The aim of our study, therefore, was to explore community perceptions on integration of animal vaccination and health education by veterinary and public health workers in the management of brucellosis in Uganda.This study used a qualitative design where six Focus Group Discussions (FGDs that were homogenous in nature were conducted, two from each sub-county, one with the local leaders, and another with pastoralists and farmers. Five Key Informant Interviews (KIIs with two public health workers and three veterinary extension workers from three sub-counties in Kiruhura district, Uganda were conducted. All FGDs were conducted in the local language and tape recorded with consent from the participants. KIIs were in English and later transcribed and analyzed using latent content data analysis method.All the groups mentioned that they lacked awareness on brucellosis commonly known as Brucella and its vaccination in animals. Respondents perceived improvement in human resources in terms of training and recruiting more health personnel, facilitation of the necessary activities such as sensitization of the communities about brucellosis, and provision of vaccines and diagnostic tests as very important in the integration process in the communities. The FGD participants also believed that community participation was crucial for sustainability and ownership of the integration process.The respondents reported limited knowledge of brucellosis and its vaccination in animals. The community members believed that mass animal vaccination in combination with health education about the disease is important and possible if it involves government and all other stakeholders such as wildlife authorities
González-Romo, Fernando; Picazo, Juan J
Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.
The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751
Vinten, Claire E K; Cobb, Kate A; Freeman, Sarah L; Mossop, Liz H
Clinical reasoning is a fundamental skill for veterinary clinicians and a competency required of graduates by the Royal College of Veterinary Surgeons. However, it is unknown how veterinary students develop reasoning skills and where strengths and shortcomings of curricula lie. This research aimed to use the University of Nottingham School of Veterinary Medicine and Science (SVMS) as a case study to investigate the development of clinical reasoning among veterinary students. The analysis was framed in consideration of the taught, learned, and declared curricula. Sixteen staff and sixteen students from the SVMS participated separately in a total of four focus groups. In addition, five interviews were conducted with recent SVMS graduates. Audio transcriptions were used to conduct a thematic analysis. A content analysis was performed on all curriculum documentation. It was found that SVMS graduates feel they have a good level of reasoning ability, but they still experience a deficit in their reasoning capabilities when starting their first job. Overarching themes arising from the data suggest that a lack of responsibility for clinical decisions during the program and the embedded nature of the clinical reasoning skill within the curriculum could be restricting development. In addition, SVMS students would benefit from clinical reasoning training where factors influencing "real life" decisions (e.g., finances) are explored in more depth. Integrating these factors into the curriculum could lead to improved decision-making ability among SVMS graduates and better prepare students for the stressful transition to practice. These findings are likely to have implications for other veterinary curricula.
Belshaw, Zoe; Robinson, Natalie J; Dean, Rachel S; Brennan, Marnie L
Dog and cat vaccination consultations are a common part of small animal practice in the United Kingdom. Few data are available describing what happens during those consultations or what participants think about their content. The aim of this novel study was to investigate the attitudes of dog and cat owners and veterinary surgeons towards the content of small animal vaccination consultations. Telephone interviews with veterinary surgeons and pet owners captured rich qualitative data. Thematic analysis was performed to identify key themes. This study reports the theme describing attitudes towards the content of the consultation. Diverse preferences exist for what should be prioritised during vaccination consultations, and mismatched expectations may lead to negative experiences. Vaccination consultations for puppies and kittens were described to have a relatively standardised structure with an educational and preventative healthcare focus. In contrast, adult pet vaccination consultations were described to focus on current physical health problems with only limited discussion of preventative healthcare topics. This first qualitative exploration of UK vaccination consultation expectations suggests that the content and consistency of adult pet vaccination consultations may not meet the needs or expectations of all participants. Redefining preventative healthcare to include all preventable conditions may benefit owners, pets and veterinary surgeons, and may help to provide a clearer structure for adult pet vaccination consultations. This study represents a significant advance our understanding of this consultation type.
Full Text Available Dog and cat vaccination consultations are a common part of small animal practice in the United Kingdom. Few data are available describing what happens during those consultations or what participants think about their content. The aim of this novel study was to investigate the attitudes of dog and cat owners and veterinary surgeons towards the content of small animal vaccination consultations. Telephone interviews with veterinary surgeons and pet owners captured rich qualitative data. Thematic analysis was performed to identify key themes. This study reports the theme describing attitudes towards the content of the consultation. Diverse preferences exist for what should be prioritised during vaccination consultations, and mismatched expectations may lead to negative experiences. Vaccination consultations for puppies and kittens were described to have a relatively standardised structure with an educational and preventative healthcare focus. In contrast, adult pet vaccination consultations were described to focus on current physical health problems with only limited discussion of preventative healthcare topics. This first qualitative exploration of UK vaccination consultation expectations suggests that the content and consistency of adult pet vaccination consultations may not meet the needs or expectations of all participants. Redefining preventative healthcare to include all preventable conditions may benefit owners, pets and veterinary surgeons, and may help to provide a clearer structure for adult pet vaccination consultations. This study represents a significant advance our understanding of this consultation type.
Robinson, Natalie J.; Dean, Rachel S.
Dog and cat vaccination consultations are a common part of small animal practice in the United Kingdom. Few data are available describing what happens during those consultations or what participants think about their content. The aim of this novel study was to investigate the attitudes of dog and cat owners and veterinary surgeons towards the content of small animal vaccination consultations. Telephone interviews with veterinary surgeons and pet owners captured rich qualitative data. Thematic analysis was performed to identify key themes. This study reports the theme describing attitudes towards the content of the consultation. Diverse preferences exist for what should be prioritised during vaccination consultations, and mismatched expectations may lead to negative experiences. Vaccination consultations for puppies and kittens were described to have a relatively standardised structure with an educational and preventative healthcare focus. In contrast, adult pet vaccination consultations were described to focus on current physical health problems with only limited discussion of preventative healthcare topics. This first qualitative exploration of UK vaccination consultation expectations suggests that the content and consistency of adult pet vaccination consultations may not meet the needs or expectations of all participants. Redefining preventative healthcare to include all preventable conditions may benefit owners, pets and veterinary surgeons, and may help to provide a clearer structure for adult pet vaccination consultations. This study represents a significant advance our understanding of this consultation type. PMID:29346332
Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.
Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R
Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.
Rappuoli, Rino; Hanon, Emmanuel
Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.
Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.
Full Text Available Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.
Armitage-Chan, E; Maddison, J; May, S A
Professionalism and professional skills are increasingly being incorporated into veterinary curricula; however, lack of clarity in defining veterinary professionalism presents a potential challenge for directing course outcomes that are of benefit to the veterinary professional. An online continuing education course in veterinary professionalism was designed to address a deficit in postgraduate support in this area; as part of this course, delegates of varying practice backgrounds participated in online discussions reflecting on the implications of professional skills for their clinical practice. The discussions surrounding the role of the veterinary professional and reflecting on strengths and weaknesses in professional skills were analysed using narrative methodology, which provided an understanding of the defining skills and attributes of the veterinary professional, from the perspectives of those involved (i.e. how vets understood their own career identity). The veterinary surgeon was understood to be an interprofessional team member, who makes clinical decisions in the face of competing stakeholder needs and works in a complex environment comprising multiple and diverse challenges (stress, high emotions, financial issues, work-life balance). It was identified that strategies for accepting fallibility, and those necessary for establishing reasonable expectations of professional behaviour and clinical ability, are poorly developed. British Veterinary Association.
... Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for... Valley Fever Virus Utilizing Reverse Genetics,'' US Provisional Application 61/042,987, filed 4/7/2008, entitled ``Recombinant Rift Valley Fever (RVF) Viruses and Method of Use,'' PCT Application PCT/US2008...
Verrinder, Joy M; Phillips, Clive J C
Veterinarians increasingly face animal ethics issues, conflicts, and dilemmas, both in practice and in policy, such as the tension between clients' and animals' interests. Little has been done to measure the capacity of veterinarians to make ethical judgments to prevent and address these issues or to identify the effectiveness of strategies to build this capacity. The objectives of this study were, first, to develop a test to identify the capacity of veterinarians to make ethical decisions in relation to animal ethics issues and, second, to assess students' perceptions of the usefulness of three methods for the development of ethical decision making. The Veterinary Defining Issues Test (VetDIT) was piloted with 88 first-year veterinary students at an Australian university. The veterinary students were at a variety of reasoning stages in their use of the Personal Interest (PI), Maintaining Norms (MN), and Universal Principles (UP) reasoning methods in relation to both human ethics and animal ethics issues and operated at a higher level of reasoning for animal than human ethics. Thirty-eight students assessed three methods for developing ethical decision-making skills and identified these as being helpful in clarifying their positions, clarifying others' positions, increasing awareness of the complexity of making ethical decisions, using ethical frameworks and principles, and improving moral reasoning skills, with two methods identified as most helpful. These methods and the VetDIT have the potential to be used as tools for development and assessment of moral judgment in veterinary education to address animal ethics issues.
Romberg, Judith; Lang, Stefan; Balks, Elisabeth; Kamphuis, Elisabeth; Duchow, Karin; Loos, Daniela; Rau, Henriette; Motitschke, Andreas; Jungbäck, Carmen
Current quality control of inactivated animal vaccines still focuses on the potency of final products in a batch-wise manner. Animal welfare concerns as well as scientific considerations have led to the '3Rs-concept' that comprises the refinement of animal procedures, the reduction of animal numbers, and the replacement of animal models. Although the 3Rs-concept has been widely accepted as a fundamental principle, the number of approved alternatives for in vivo tests is still limited. To promote further progress, the international scientific workshop 'Potency Testing of Veterinary Vaccines: The Way from in vivo to in vitro' was held at the Paul-Ehrlich-Institut in Langen, Germany, on 01-03 December 2010. More than 130 participants from industry, academia and regulatory authorities discussed the current state of the 3Rs-concept, examples of its successful implementation as well as still existing hurdles. Special emphasis was laid on the 'consistency approach' that aims to ensure relevant quality attributes of vaccine batches by in vitro analyses during production rather than by in vivo potency tests on the final product. This report provides an overview of the insights gained, including the recommendations produced at the end of the workshop. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.
Rodríguez-Limas, William A; Pastor, Ana Ruth; Esquivel-Soto, Ernesto; Esquivel-Guadarrama, Fernando; Ramírez, Octavio T; Palomares, Laura A
Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD50) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Objective: This paper sets out to highlight the ongoing need for integrated teaching of business skills in the veterinary curriculum.Background: In response to the changing environment of the veterinary profession, it is important to understand the future needs of veterinary practitioners. While changes to the veterinary curriculum have been made in recent years, they have been highly varied across schools and little evidence is available on how these have improved students’ non-technical skills, knowledge, aptitudes, and attitudes. Evidentiary value: This literature review of 23 papers provides a solid basis for the further development of knowledge on business management issues in veterinary curricula. The impact on practice from our findings is substantial. The role of clinicians in academia is recognised as a primary source of engaging students with business management through their day-to-day teaching. Furthermore, the role of first-opinion vets who take on placement students (known as extra mural studies or ‘EMS’ in the UK cannot be underestimated as they play an essential role in ensuring that students perceive business skills with the same importance as clinical skills.Methods: This research draws on the findings of 23 papers that emerged as relevant from the structured literature search. The search yielded 124 papers but many were excluded because they focused on issues beyond the search strategy, did not report empirical findings so were based largely on discussion and conjecture, were not about the undergraduate veterinary curriculum, were not written in English or were not related to business teaching.Results: Employers of recent graduates highly value business skills, and often base their hiring decision on non-technical skills, rather than clinical skills. While changes to the veterinary curriculum have been made to include more non-technical training by individual veterinary schools, it is unclear how effective these
Alders, R G; Bagnol, B; Young, M P; Ahlers, C; Brum, E; Rushton, J
The challenges and constraints to vaccinating poultry in areas where adequate infrastructure and human resources are lacking are addressed in both a technical and a socioeconomic framework. The key issues discussed are: (1) selection of an appropriate vaccine and vaccination technique, including the advantages and disadvantages of a combined vaccine against highly pathogenic avian influenza (HPAI) and Newcastle disease and addressing the differences between endemic disease and emergency disease control; (2) vaccine conservation and distribution; (3) evaluation of the flocks to be vaccinated in terms of their disease status, immunocompetence and production systems; (4) design of effective information, education and communication materials and methods with and for veterinary and extension staff as well as commercial and smallholder producers and community vaccinators in rural areas; (5) evaluation and monitoring systems for technical and socioeconomic factors that affect vaccination; (6) support and coordination of and by relevant public and private agencies; (7) the role of simultaneous implementation of other control activities in addition to vaccination; (8) the importance of assessing the costs and cost-effectiveness of various approaches to the control of HPAI, including the prevention of other endemic killer diseases and options for cost-sharing; (9) evaluation of the incentives for poultry-holders, vaccinators and vaccine producers to contribute to and participate in effective vaccination campaigns; and (10) policy development and the organizational framework for short- and long-term implementation and communication to decision-makers.
Hubbert, William T.
The program aims at training veterinarians, with interdepartmental faculty participation the rule rather than the exception. Included in the curriculum are: avian medicine, herd health management, veterinary public health, veterinary food hygiene, and regulatory veterinary medicine. (LBH)
Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence
A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.
Moore, D A; Klingborg, D J
Leadership skills are important for many facets of professional life, but no known leadership training programs exist in North American veterinary schools. It was the purpose of this project to develop, deliver, and evaluate a leadership program for first-year veterinary students. Leadership attributes emphasized in the course included effective communication, openness to learning from others, self-awareness, commitment beyond self-interest, motivation, decision making, understanding issue complexity, and team building. The five-day course was delivered to 21 new veterinary students randomly selected just prior to their first-year orientation in the fall of 2000. Participants ranked themselves higher than non-participants in a post-course evaluation on their ability to be effective leaders. Participants reported an increase in self-confidence and a clearer understanding of their leadership roles. Participants also noted new support systems among co-participants and expressed a new ability to consider complex issues more broadly. Most reported that they frequently used enhanced skills in giving and receiving feedback and team building. Other leadership tools identified as valuable included negotiation, group dynamics, a structured approach to problem solving, time management, and an awareness of personal learning style preferences as a means to improve communication.
The Nigerian Veterinary Journal (NVJ) has been in existence since 1971. ... dogs diagnosed with parvovirus enteritis in some veterinary clinics in Nigeria · EMAIL ... Rabies vaccination status among occupationally exposed humans in Nigeria ...
Wolfe, Daniel N; Heppner, D Gray; Gardner, Shea N; Jaing, Crystal; Dupuy, Lesley C; Schmaljohn, Connie S; Carlton, Kevin
Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. © The American Society of Tropical Medicine and Hygiene.
Chellapandi, Paulchamy; Prisilla, Arokiyasamy
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced by this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships with them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems in eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Dozier, Samantha; Brown, Jeffrey; Currie, Alistair
Simple Summary Many vaccines are tested for quality in experiments that require the use of large numbers of animals in procedures that often cause significant pain and distress. Newer technologies have fostered the development of vaccine quality control tests that reduce or eliminate the use of animals, but the availability of these newer methods has not guaranteed their acceptance by regulators or use by manufacturers. We discuss a strategic approach that has been used to assess and ultimately increase the use of non-animal vaccine quality tests in the U.S. and U.K. Abstract In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches. PMID:26486625
YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.
Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309
Full Text Available The article presents medical and social aspects of immune prophylaxis of infectious diseases; the history of vaccines and vaccination is presented, as well as perspectives of development of vaccine prophylaxis.
Martins, Bavari, Zika Vaccine Development 1 Zika Vaccine Development: Flavivirus Foils Martins KAO, Bavari S. The current Zika virus...States government. The rapid response to Zika is perhaps the first of its kind, and it undoubtedly has been made possible by the lessons learned from...the response to the 2014 Ebola virus outbreak in West Africa. However, Zika virus is not Ebola virus. As of February 2016 there were only 296
Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.
Full Text Available Visceral leishmaniasis (VL caused by Leishmania donovani and Leishmania infantum/ chagasi represents the second most challenging infectious disease worldwide, affecting nearly 500,000 people and 60,000 deaths annually. Zoonotic VL (ZVL caused by L. infantum is re-emergent canid zoonoses which represents a complex epidemiological cycle in New world where domestic dogs serve as reservoir host responsible for potentially fatal human infection where dog culling is the only control measure for eliminating reservoir host. Lifelong immunity in human against reinfection has motivated several attempts in developing prophylactic vaccines against the disease but very few have progressed beyond experimental stage. Absence of any licensed vaccine along with high toxicity and increasing resistance to the current chemotherapeutic drugs has further complicated the situation in endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge about pathogenesis, immune response and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine targets, their developmental status and future prospects in a quest for rational vaccine development against VL. In addition, several challenges such as safety issues, a renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing effective vaccines
Full Text Available Treating cancer with vaccines has been a challenging field of investigation since the 1950s. Over the years, the lack of effective active immunotherapies has led to the development of numerous novel strategies. However, the use of therapeutic cancer vaccines may be on the verge of becoming an effective modality. Recent phase II/III clinical trials have achieved hopeful results in terms of overall survival. Yet despite these encouraging successes, in general, very little is known about the basic immunological mechanisms involved in vaccine immunotherapy. Gaining a better understanding of the mechanisms that govern the specific immune responses (i.e., cytotoxic T lymphocytes, CD4 T helper cells, T regulatory cells, cells of innate immunity, tumor escape mechanisms elicited by each of the various vaccine platforms should be a concern of cancer vaccine clinical trials, along with clinical benefits. This review focuses on current strategies employed by recent clinical trials of therapeutic cancer vaccines and analyzes them both clinically and immunologically.
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...
For vaccine production, recombinant antigens must be protective. Identifying protective antigens or candidate antigens is an essential precursor to vaccine development. Even when a protective antigen has been identified, cloning of its gene does not lead directly to vaccine development. The fimbrial protein of Dichelobacter nodosus, the agent of foot-rot in ruminants, was known to be protective. Recombinant vaccines against this infection are ineffective if expressed protein subunits are not assembled as mature fimbriae. Antigenic competition between different, but closely related, recombinant antigens limited the use of multivalent vaccines based on this technology. Recombinant antigens may need adjuvants to enhance response. DNA vaccines, potentiated with genes for different cytokines, may replace the need for aggressive adjuvants, and especially where cellular immunity is essential for protection. The expression of antigens from animal pathogens in plants and the demonstration of some immunity to a disease like rinderpest after ingestion of these, suggests an alternative approach to vaccination by injection. Research on disease pathogenesis and the identification of candidate antigens is specific to the disease agent. The definition of expression systems and the formulation of a vaccine for each disease must be followed by research to establish safety and efficacy. Where vaccines are based on unique gene sequences, the intellectual property is likely to be protected by patent. Organizations, licensed to produce recombinant vaccines, expect to recover their costs and to make a profit. The consequence is that genetically-derived vaccines are expensive. The capacity of vaccines to help animal owners of poorer countries depends not only on quality and cost but also on the veterinary infrastructure where they are used. Ensuring the existence of an effective animal health infrastructure in developing countries is as great a challenge for the developed world as
E.J.M. Rooijakkers; J.H.M. Nieuwenhuijs; A.A. Vermeulen; A.D.M.E. Osterhaus (Albert); G. van Steenis (Bert)
textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and
Martin, Michael; Tummons, John; Ball, Anna; Bird, William
The purpose of this bounded single case study was to explore how an urban high school veterinary program impacted students' affective skill development. The program was unique because students were required to participate in internships with local animal care businesses and care for animals within the school veterinary laboratory. The…
... it requires ultra-cold storage (-196° C), intravenous administration by veterinary health professionals, ... It is expected that by the end of the project, the production process of the new heartwater vaccine will ... Agricultural Research Council.
The Global Alliance for Livestock Veterinary Medicines estimates that every year, ... because antibiotic treatment does not eliminate the bacterium and sanitary ... protective Mccp antigens, and be used either as a live or inactivated vaccine.
Full Text Available In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.
Dozier, Samantha; Brown, Jeffrey; Currie, Alistair
In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.
Liu, Guangjin; Zhu, Jielian; Chen, Kangming; Gao, Tingting; Yao, Huochun; Liu, Yongjie; Zhang, Wei; Lu, Chengping
Vaccination is a widely accepted and effective method to prevent most pathogenic diseases in aquaculture. Various species of tilapia, especially Nile tilapia Oreochromis niloticus, are farmed worldwide because of their high consumer demand. Recently, the tilapia-breeding industry has been hampered by outbreaks of Streptococcus agalactiae infection, which cause high mortality and huge economic losses. Many researchers have attempted to develop effective S. agalactiae vaccines for tilapia. This review provides a summary of the different kinds of S. agalactiae vaccines for tilapia that have been developed recently. Among the various vaccine types, inactivated S. agalactiae vaccines showed superior protection efficiency when compared with live attenuated, recombinant and DNA vaccines. With respect to vaccination method, injecting the vaccine into tilapia provided the most effective immunoprotection. Freund's incomplete adjuvant appeared to be suitable for tilapia vaccines. Other factors, such as immunization duration and number, fish size and challenge dose, also influenced the vaccine efficacy.
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen
This article traces the development of agricultural science at the Onderstepoort Veterinary Institute, near Pretoria, from its founding in 1908 until the 1950s, by which time many enzootic and epizootic diseases had either been eradicated, or were largely controllable through various forms of prophylaxis. The Institute demonstrated the political and economic significance attributed to the pastoral industry in South Africa and the conviction that scientific discoveries could increase output. During this period, researchers explicated the aetiology and provenance of hitherto mysterious diseases such as lamsiekte, geeldikkop and African horsesickness. They developed vaccines, some of which were adopted internationally. The nature of their investigations showed that veterinary science increasingly entailed more than just progress in biomedical procedures. Ecological factors, in particular the nutritional state of the veld, became a priority from the 1920s onwards as veterinarians saw their function as promoting animal health as well as eliminating disease. Dealing with contagious infections also incorporated less welcome, and at times controversial, approaches to disease control. The imposition of pastoral regulations illustrated the expanding powers of the South African state, founded on presumptions of scientific legitimacy. The article also explores the contribution made by African communities and settler farmers to the institutionalisation of veterinary knowledge, as well as the role South African researchers played in the evolution of a colonial, as well as an increasingly international, scientific culture.
Seo, Ho Seong
One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.
Veterinary immunologists have expanded understanding of the immune systems for our companion animals and developed new vaccines and therapeutics. This manuscript summarizes the highlights of the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto,...
Lalsiamthara, Jonathan; Lee, John Hwa
The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella .
Rooijakkers, E.J.M.; Nieuwenhuijs, J.H.M.; Vermeulen, A.A.; Osterhaus, Albert; Steenis, Bert
textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and nucleoprotein (NP) contents were determined in an antigen competition ELISA. The GP content proved to correlate well with the potency found in the mouse potency test (r = 0.95, p < 0.01), whereas no su...
Golden, Olwen; Hanlon, Alison J
Veterinary behaviour medicine should be a foundation subject of the veterinary curriculum because of its wide scope of applications to veterinary practice. Private practitioners are likely to be the primary source of information on animal behaviour for most pet owners, however studies indicate that behavioural issues are not frequently discussed during companion animal consultations and many practitioners lack confidence in dealing with behavioural problems, likely due to poor coverage of this subject in veterinary education.There is a need to identify learning outcomes to support day one competences in veterinary behaviour medicine and these should be informed by practice-based evidence. This study aimed to investigate the nature and frequency of behavioural queries experienced by veterinary professionals in Ireland, the provision of behavioural services at companion animal practices, behaviour referral practices and challenges associated with providing a behaviour service. Two online surveys were developed, one for private veterinary practitioners (PVP) and one for veterinary nurses (VN). Invitations to participate were distributed using contact details from the Premises Accreditation Scheme database on the Veterinary Council of Ireland website. Thirty-eight PVPs and 69 VNs completed the survey. Results indicated that less than half of companion animal practices offer behavioural consults and under a third of practices provide training and socialization events. Over half of the practices surveyed have referred cases to a behavioural specialist.The majority of respondents encountered behavioural queries weekly. Ninety-eight percent reported receiving queries regarding dog behaviour. Toilet training and unruly behaviour were two issues encountered frequently. Behavioural issues in cats were also common. House soiling and destructive behaviour were the problems most frequently encountered by respondents.The two most commonly cited barriers to providing behavioural
Marcos Roberto A. Ferreira
Full Text Available Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that is present in the gastrointestinal tract of healthy humans and animals. This bacterium produces up to 18 toxins. The species is classified into five toxinotypes (A–E according to the toxins that the bacterium produces: alpha, beta, epsilon, or iota. Each of these toxinotypes is associated with myriad different, frequently fatal, illnesses that affect a range of farm animals and humans. Alpha, beta, and epsilon toxins are the main causes of disease. Vaccinations that generate neutralizing antibodies are the most common prophylactic measures that are currently in use. These vaccines consist of toxoids that are obtained from C. perfringens cultures. Recombinant vaccines offer several advantages over conventional toxoids, especially in terms of the production process. As such, they are steadily gaining ground as a promising vaccination solution. This review discusses the main strategies that are currently used to produce recombinant vaccines containing alpha, beta, and epsilon toxins of C. perfringens, as well as the potential application of these molecules as vaccines for mammalian livestock animals.
Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N
The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.
San Miguel, Sandra F.; Parker, Loran Carleton; Adedokun, Omolola A.; Burgess, Wilella D.; Cipriani Davis, Kauline S.; Blossom, Thaddaeus D.; Schneider, Jessica L.; Mennonno, Ann M.; Ruhl, Joseph D.; Veatch, Jennifer H.; Wackerly, Amy J.; Shin, Soo Yeon; Ratliff, Timothy L.
Workforce development strategies to educate, inform, and diversify the veterinary profession of the future must begin with children in elementary school. This manuscript provides a description of the Fat Dogs and Coughing Horses program, which takes a multifaceted approach toward informing young students, beginning in first grade, about the interesting work and career opportunities available in the field of veterinary medicine. The program, a collaboration among Purdue University and Indiana ...
Bulkhanov, R.U.; Butaev, M.K.; Mirzaev, B.Sh.; Ryasnyanskiy, I.V.; Yuldashev, R.Yu.
Full text: The process based on stimulated action of ionized radiation, change of quality of agricultural goods and row materials, biocides including bactericide action of ionized radiation are among the methods of radiation biotechnology, which can be applied in agriculture. We used the bactericide action of ionized radiation in technological process for creation of fundamentally new preparation possessed by by immunogenic properties and named as 'radio vaccine'. This term is well known and frequently used in scientific papers in the field of applied radiobiology. It is well known that physical (thermal) and chemical actions are used for preparation of vaccine for veterinary. It was noted that this process resulted in destruction of antigenic structure of bacteria cells, with are responsible for immunity creation. The possibility of virulence reduction at constant immunogenic properties of microorganism and keeping its antigenic structure can be achieved by using ionized radiation as one of the factor, which influences on bacteria. Taking into account the necessity of vaccine improvement and increase of quantity of associated vaccine one of the most important problems of veterinary science and particle is creation of vaccines of new generation which are characterized by the ability to form immunity against several diseases of agricultural animals. As a result of many-years investigations using gamma rays radiations in UzSRIV (laboratory of radiobiology) the radiation biotechnology of vaccine preparation was developed. These vaccines are necessary for practical application. Radiation biotechnology allows to prepare high-effective mono-, associated and polyvalent radio vaccines against widespread infection diseases of agricultural animals especially cubs (calves, lambs, young pigs). On the basis of developed radiation biotechnology there were prepared the following vaccines: 'Associated radio vaccine against colibacteriosis and salmonellosis of small horned cattle
Hammond, Jennifer A; Hancock, Jason; Martin, Margaret S; Jamieson, Susan; Mellor, Dominic J
The ability to cope with ambiguity and feelings of uncertainty is an essential part of professional practice. Research with physicians has identified that intolerance of ambiguity or uncertainty is linked to stress, and some authors have hypothesized that there could be an association between intolerance of ambiguity and burnout. We describe the adaptation of the TAMSAD (Tolerance of Ambiguity in Medical Students and Doctors) scale for use with veterinary students. Exploratory factor analysis supports a uni-dimensional structure for the Ambiguity tolerance construct. Although internal reliability of the 29-item TAMSAD scale is reasonable (α=.50), an alternative 27-item scale (drawn from the original 41 items used to develop TAMSAD) shows higher internal reliability for veterinary students (α=.67). We conclude that there is good evidence to support the validity of this latter TAVS (Tolerance of Ambiguity in Veterinary Students) scale to study ambiguity tolerance in veterinary students.
Crompton, Peter D; Pierce, Susan K; Miller, Louis H
Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.
Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela
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, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444
Jacqueline M. Miller
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, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.
Gay, C G; Salt, J; Balaski, C
Veterinary pharmaceutical products generated 14.5 billion U.S. Dollars (USD) in worldwide sales in 2000, with biological products contributing 16.2 percent or 2.3 billion USD. The leading biological products were foot-and-mouth disease (FMD) vaccines, with 284 million USD in sales, representing 26.4 percent of the entire livestock biological business. Despite the potential opportunities for the biologicals industry, non-vaccination policies and undefined control and eradication strategies have deterred the private sector from significant investments in the research and development of vaccines against List A diseases. The primary research focus remains vaccines for infectious diseases that have an impact on current domestic herd health management systems. Changing the vaccine paradigm, investing in new technologies, and creating the future by integrating into key alliances with producers and regulatory authorities will be paramount in protecting our poultry and livestock industries against highly infectious diseases and potential acts of bioterrorism.
Seguino, Alessandro; Seguino, Ferruccio; Eleuteri, Antonio; Rhind, Susan M
Veterinary surgeons working on farms and food-processing establishments play a fundamental role in safeguarding both public health and the welfare of animals under their care. An essential part of veterinary public health (VPH) undergraduate training in the UK involves students undertaking placements within abattoirs, a practice that remains vital to the educational experience of future veterinary professionals. However, several issues have adversely affected the ability of students to gain such extramural placements. For this reason, the Virtual Slaughterhouse Simulator (VSS) was developed to strengthen and enhance undergraduate VPH teaching at the Royal (Dick) School of Veterinary Studies, enabling students to explore a realistic abattoir work environment with embedded educational activities. The aim of this research project was to evaluate the VSS as a teaching and learning tool for training and educating veterinary students. Ninety-eight final-year veterinary students engaged with the prototype VSS, followed by assessment of their knowledge and behavior when faced with a "real-life" abattoir situation. Further evaluation of their experiences with the VSS was carried out using questionnaires and focus groups. The results of this investigation show that there is the potential for the VSS to enhance the student learning experience in basic abattoir procedures. This innovative tool provides a visually based learning resource that can support traditional lectures and practical classes and can also be used to stimulate interactive problem-solving activities embedded in the relevant context.
Bioinformatics has advanced the course of research and future veterinary vaccines development because it has provided new tools for identification of vaccine targets from sequenced biological data of organisms. In Nigeria, there is lack of bioinformatics training in the universities, expect for short training courses in which ...
Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena
A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.
Marchioro, Silvana Beutinger; Simionatto, Simone; Dellagostin, Odir
Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), a disease that affects swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of the disease. Research using genome-based approach has the potential to elucidate the biology and pathogenesis of M. hyopneumoniae and contribute to the development of more effective vaccines. Here, we describe the protocol for developing M. hyopneumoniae recombinant vaccines using reverse vaccinology approaches.
Byron, Julie K; Johnson, Susan E; Allen, L Clare V; Brilmyer, Cheryl; Griffiths, Robert P
There is an increasing demand in veterinary education to engage students, teach and reinforce clinical reasoning, and provide access anytime/anywhere to quality learning opportunities. In addition, accrediting bodies are asking for more concrete documentation of essential clinical-skills outcomes. Unfortunately, during the clinical year in a referral hospital setting, students are at the mercy of chance regarding the types of cases they will encounter and the opportunities they will have to participate. Patient- and case-simulation technology is becoming more popular as a way to achieve these objectives in human and veterinary medical education. Many of the current options available to the veterinary medical education community to develop virtual-patient cases are too time-consuming, cost prohibitive, or difficult for the instructor or learner to use. In response, we developed a learning tool, Case Manager, which is low-cost and user-friendly. Case Manager was designed to meet the demands of veterinary education by providing students with an opportunity to cultivate clinical reasoning skills and allowing for real-time student feedback. We launched a pilot test with 37 senior veterinary medical students as part of their Small Animal Internal Medicine clinical rotation. Students reported that Case Manager increased their engagement with the material, improved diagnostic and problem-solving skills, and broadened their exposure to a variety of cases. In addition, students felt that Case Manager was superior to a more traditional, less interactive case presentation format.
Vaccine development to eliminate flaviviral infections has been marked by uneven progress and a large number of setbacks. To date, no single approach has proved successful in leading to vaccine development against a wide range of flaviviruses, but the application of modern techniques to the problem is opening up new ...
Hardham, J M; Lamichhane, C M
Veterinary diagnostic products generated ~$3 billion US dollars in global sales in 2010. This industry is poised to undergo tremendous changes in the next decade as technological advances move diagnostic products from the traditional laboratory-based and handheld immunologic assays towards highly technical, point of care devices with increased sensitivity, specificity, and complexity. Despite these opportunities for advancing diagnostic products, the industry continues to face numerous challenges in developing diagnostic products for emerging and foreign animal diseases. Because of the need to deliver a return on the investment, research and development dollars continue to be focused on infectious diseases that have a negative impact on current domestic herd health, production systems, or companion animal health. Overcoming the administrative, legal, fiscal, and technological barriers to provide veterinary diagnostic products for the National Veterinary Stockpile will reduce the threat of natural or intentional spread of foreign diseases and increase the security of the food supply in the US.
Yee, Pinn Tsin Isabel; Poh, Chit Laa
The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71) and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1) vaccine and virus-like particles (VLPs). The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design. PMID:26729152
The past decennia, veterinary medical education worldwide has gone through some rapid and major developments. Motivation for these developments were, among others, the explosion of (bio) medical knowledge, the related problem of curriculum overload and the mismatch between university and the
This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and
Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency
Mori, Akihiro; Oda, Hitomi; Onozawa, Eri; Shono, Saori; Sako, Toshinori
This study evaluated the accuracy of a newly developed veterinary portable blood glucose meter (PBGM) with hematocrit correction in dogs and cats. Sixty-one dogs and 31 cats were used for the current study. Blood samples were obtained from each dog and cat one to six times. Acceptable results were obtained in error grid analysis between PBGM and reference method values (glucose oxidation methods) in both dogs and cats. Bland-Altman plot analysis revealed a mean difference between the PBGM value and reference method value of -1.975 mg/dl (bias) in dogs and 1.339 mg/dl (bias) in cats. Hematocrit values did not affect the results of the veterinary PBGM. Therefore, this veterinary PBGM is clinically useful in dogs and cats.
Rumbo, Martin; Hozbor, Daniela
Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized.
and Aji, T. G.. 1. 1Faculty of Veterinary Medicine, University of Maiduguri, Nigeria. ... limited nervous, muscle and skeletal systems development ... samples. Colloid area/volume and perimeter: This ..... BANKS, W. J., (1993): Applied Veterinary.
Raffan, Hazel; Guevar, Julien; Poyade, Matthieu; Rea, Paul M
Current methods used to communicate and present the complex arrangement of vasculature related to the brain and spinal cord is limited in undergraduate veterinary neuroanatomy training. Traditionally it is taught with 2-dimensional (2D) diagrams, photographs and medical imaging scans which show a fixed viewpoint. 2D representations of 3-dimensional (3D) objects however lead to loss of spatial information, which can present problems when translating this to the patient. Computer-assisted learning packages with interactive 3D anatomical models have become established in medical training, yet equivalent resources are scarce in veterinary education. For this reason, we set out to develop a workflow methodology creating an interactive model depicting the vasculature of the canine brain that could be used in undergraduate education. Using MR images of a dog and several commonly available software programs, we set out to show how combining image editing, segmentation and surface generation, 3D modeling and texturing can result in the creation of a fully interactive application for veterinary training. In addition to clearly identifying a workflow methodology for the creation of this dataset, we have also demonstrated how an interactive tutorial and self-assessment tool can be incorporated into this. In conclusion, we present a workflow which has been successful in developing a 3D reconstruction of the canine brain and associated vasculature through segmentation, surface generation and post-processing of readily available medical imaging data. The reconstructed model was implemented into an interactive application for veterinary education that has been designed to target the problems associated with learning neuroanatomy, primarily the inability to visualise complex spatial arrangements from 2D resources. The lack of similar resources in this field suggests this workflow is original within a veterinary context. There is great potential to explore this method, and introduce
Cawein, Andrea; Emini, Emilio; Watson, Michael; Dailey, Joanna; Donnelly, John; Tresnan, Dina; Evans, Tom; Plotkin, Stanley; Gruber, William
Despite the success of vaccines in reducing the morbidity and mortality associated with infectious diseases, many infectious diseases, both newly emerging and well known, lack vaccines. The global capability for beginning-to-end vaccine development has become limited, primarily owing to a scarcity of human capital necessary to guide the development of novel vaccines from the laboratory to the marketplace. Here, we identify and discuss the gaps in human capital necessary for robust vaccine development and make recommendations to begin to address these deficiencies. © 2017 New York Academy of Sciences.
Speiser Daniel E
Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.
Baillie, Sarah; Kinnison, Tierney; Forrest, Neil; Dale, Vicki H M; Ehlers, Jan P; Koch, Michael; Mándoki, Mira; Ciobotaru, Emilia; de Groot, Esther; Boerboom, Tobias B B; van Beukelen, Peter
An online professional network for veterinarians, veterinary students, veterinary educationalists, and ICT (Information and Communication Technology) educationalists is being developed under the EU (European Union) Lifelong Learning Programme. The network uses Web 2.0, a term used to describe the new, more interactive version of the Internet, and includes tools such as wikis, blogs, and discussion boards. Focus groups conducted with qualified and student veterinarians within the project's five founding countries (The Netherlands, Germany, United Kingdom, Hungary, Romania) demonstrated that online professional communities can be valuable for accessing information and establishing contacts. Online networks have the potential to overcome common challenges to face-to-face communities-such as distance, cost, and timing-but they have their own drawbacks, such as security and professionalism issues. The Network Of Veterinary ICt in Education (NOVICE) was developed using Elgg, an open-source, free social networking platform, after several software options had been considered. NOVICE aims to promote the understanding of Web 2.0, confidence to use social software tools, and participation in an online community. Therefore, the Web site contains help sections, Frequently Asked Questions, and access to support from ICT experts. Five months after the network's launch (and just over one year into the project) 515 members from 28 countries had registered. Further research will include analysis of a core group's activities, which will inform ongoing support for and development of informal, lifelong learning in a veterinary context.
Arya, Jaya; Prausnitz, Mark R
Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries. Copyright © 2015. Published by Elsevier B.V.
Nascimento, I.P.; Leite, L.C.C. [Centro de Biotecnologia, Instituto Butantan, São Paulo, SP (Brazil)
Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.
Full Text Available Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.
Nascimento, I.P.; Leite, L.C.C.
Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks
San Miguel, Sandra F; Carleton Parker, Loran; Adedokun, Omolola A; Burgess, Wilella D; Cipriani Davis, Kauline S; Blossom, Thaddaeus D; Schneider, Jessica L; Mennonno, Ann M; Ruhl, Joseph D; Veatch, Jennifer H; Wackerly, Amy J; Shin, Soo Yeon; Ratliff, Timothy L
Workforce development strategies to educate, inform, and diversify the veterinary profession of the future must begin with children in elementary school. This article provides a description of the Fat Dogs and Coughing Horses program, which takes a multifaceted approach toward informing young students, beginning in first grade, about the interesting work and career opportunities available in the field of veterinary medicine. The program, a collaboration among Purdue University and Indiana public schools, is supported by a Science Education Partnership Award from the Office of Research Infrastructure Programs, a component of the National Institutes of Health. The overall goal of the program is to provide formal and informal educational opportunities for students, parents, teachers, and the public about the science involved in keeping people and their animals healthy. Examples of health concerns that impact both people and their pets are used to inform and excite children about careers in the health sciences. The program resulted in (1) curricula for students in Grades 1-3, 6, and 9; (2) four children's books and a set of collectible cards which highlight veterinarians, veterinary technicians, and research scientists who work with animals; and (3) four traveling museum-level quality exhibits. Preliminary assessment data has shown that the implementation of the curricula enhanced student science learning and science attitudes and interests. The program provides evidence that partnerships among professionals in veterinary medicine and K-12 education can result in impactful workforce development programs.
Prendergast, Andrew J.
Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge. PMID:25964453
Full Text Available West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.
Foster, Neil; Elsheikha, Hany M
Despite the increasing knowledge of the immunobiology and epidemiology of parasitic helminths of the gastrointestinal system and the cardiorespiratory system, complications arising from infections of animals and humans with these parasites are a major clinical and economic problem. This has been attributed to the high incidence of these parasites, the widespread emergence of multi-drug resistant parasite strains and the lack of effective vaccines. Efforts to develop and produce vaccines against virtually all helminths (with the exception of Dictyocaulus viviparus and some cestode species) have been hindered by the complexity of the host-parasite relationship, and incomplete understanding of the molecular and immune regulatory pathways associated with the development of protective immunity against helminths. Novel genomic and proteomic technologies have provided opportunities for the discovery and characterisation of effector mechanisms and molecules that govern the host-parasite interactions in these two body systems. Such knowledge provided clues on how appropriate and protective responses are elicited against helminths and, thus, may lead to the development of effective therapeutic strategies. Here, we review advances in the immune response to selected helminths of animal health significance, and subsequent vaccine potential. The topics addressed are important for understanding how helminths interact with host immune defences and also are relevant for understanding the pathogenesis of diseases caused by helminths.
Latin America undoubtedly has comparative advantages in the fields of animal production, animal health and the production of food of animal origin. However, countries in Latin America must build on these strengths if the continent is to become more competitive and be able to deal with the complexities of world markets. To do this, Veterinary Services must define their objectives and establish quality standards on which to base their work. For this to occur, the State must create well-defined regulations, establish systems of audit and find ways of working which allow for a high degree of coordination and collaboration between the public and private sectors. This should be done within a framework of a quality assurance system, which allows for responsible accreditation and independent audit and evaluation. The author discusses the approaches of the different countries in the region to animal health, zoonosis, food safety, veterinary drugs control, animal welfare and export-import control. All programmes relating to these issues must be based on technical information gained through epidemiological surveillance, the network of diagnostic laboratories, quarantine systems, risk analysis, identification and traceability of animals and animal products, registration and control of veterinary drugs, and food safety research. In some countries these systems are already being developed. Maintaining good international relations and cooperating with neighbouring countries is always a challenge for official Veterinary Services and international organisations such as the OIE (World organisation for animal health) have a key role to play in facilitating these relationships.
Muma, John B; Mwacalimba, Kennedy K; Munang'andu, Hetron M; Matope, Gift; Jenkins, Akinbowale; Siamudaala, Victor; Mweene, Aaron S; Marcotty, Tanguy
Few studies have explicitly examined the linkages between human health, animal disease control and poverty alleviation. This paper reviews the contribution that veterinary medicine can make to poverty alleviation in sub-Saharan Africa. Our analysis attempts to explore aspects of this contribution under five themes: food production; food safety; impact and control of zoonotic infections; promotion of ecotourism; and environmental protection. While these areas of human activity have, more or less, fallen under the influence of the veterinary profession to varying degrees, we attempt to unify this mandate using a 'One Health' narrative, for the purpose of providing clarity on the linkages between the veterinary and other professions, livestock production and poverty alleviation. Future opportunities for improving health and reducing poverty in the context of developing African countries are also discussed. We conclude that veterinary science is uniquely positioned to play a key role in both poverty reduction and the promotion of health, a role that can be enhanced through the reorientation of the profession's goals and the creation of synergies with allied and related professions.
John B. Muma
Full Text Available Few studies have explicitly examined the linkages between human health, animal disease control and poverty alleviation. This paper reviews the contribution that veterinary medicine can make to poverty alleviation in sub-Saharan Africa. Our analysis attempts to explore aspects of this contribution under five themes: food production; food safety; impact and control of zoonotic infections; promotion of ecotourism; and environmental protection. While these areas of human activity have, more or less, fallen under the influence of the veterinary profession to varying degrees, we attempt to unify this mandate using a 'One Health' narrative, for the purpose of providing clarity on the linkages between the veterinary and other professions, livestock production and poverty alleviation. Future opportunities for improving health and reducing poverty in the context of developing African countries are also discussed. We conclude that veterinary science is uniquely positioned to play a key role in both poverty reduction and the promotion of health, a role that can be enhanced through the reorientation of the profession's goals and the creation of synergies with allied and related professions.
Full Text Available Raju Sunagar, Sudeep Kumar, Brian J Franz, Edmund J Gosselin Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA Abstract: Francisella tularensis (Ft is a gram-negative intercellular pathogen and category A biothreat agent. However, despite 15 years of strong government investment and intense research focused on the development of a US Food and Drug Administration-approved vaccine against Ft, the primary goal remains elusive. This article reviews research efforts focused on developing an Ft vaccine, as well as a number of important factors, some only recently recognized as such, which can significantly impact the development and evaluation of Ft vaccine efficacy. Finally, an assessment is provided as to whether a US Food and Drug Administration-approved Ft vaccine is likely to be forthcoming and the potential means by which this might be achieved. Keywords: Sex bias, media impact, differential protection, cellular immunity, humoral immunity
Fahdel M. Housawi
Full Text Available The epidemiology of orf virus infection in Saudi Arabia (SA has been researched since 1990. The results obtained during this period indicate that the disease is widespread, has great economic impact and that no vaccine has been used against it. The present study compares the immunogenicity and protective efficacy of three locally developed live orf virus vaccines. Two of them differ in their passage history in Vero cell culture and the third was used as a virulent virus in glycerine buffer. To the best of the authors’ knowledge, no similar comparative study has been conducted in the Middle East utilising three types of vaccines prepared from the same virus strain. Selection of the candidate seed orf virus and performance of the quality control tests were as laid out by the OIE for veterinary vaccine production. The vaccine seed virus was a field orf virus isolated from a previous orf outbreak in Saudi Arabia. A simple novel formula was developed to calculate the rate of reduction in the healing time (RHT % in the challenged sheep. This allowed direct comparison of the efficacy of the three types of vaccines employed in the present study. The efficacy of each vaccine was tested on a cohort of local Noemi sheep.
Verrinder, Joy M; Phillips, Clive J C
Little has been done to assess veterinarians' moral judgment in relation to animal ethics issues. Following development of the VetDIT, a new moral judgment measure for animal ethics issues, this study aimed to refine and further validate the VetDIT, and to identify effects of teaching interventions on moral judgment and changes in moral judgment over time. VetDIT-V1 was refined into VetDIT-V2, and V3 was developed as a post-intervention test to prevent repetition. To test these versions for comparability, veterinary and animal science students (n=271) were randomly assigned to complete different versions. The VetDIT discriminates between stages of moral judgment, condensed into three schemas: Personal Interest (PI), Maintaining Norms (MN), and Universal Principles (UP). There were no differences in the scores for MN and UP between the versions, and we equated PI scores to account for differences between versions. Veterinary science students (n=130) who completed a three-hour small-group workshop on moral development theory and ethical decision making increased their use of UP in moral reasoning, whereas students (n=271) who received similar information in a 50-minute lecture did not. A longitudinal comparison of matched first- and third-year students (n=39) revealed no moral judgment development toward greater use of UP. The VetDIT is therefore useful for assessing moral judgment of animal and human ethics issues in veterinary and other animal-related professions. Intensive small-group workshops using moral development knowledge and skills, rather than lectures, are conducive to developing veterinary students' moral judgment.
Sargeant, J. M.; O'Connor, A. M.; Dohoo, I. R.
Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. Our objective was to develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses...... unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. We conducted a consensus meeting with 17 experts in Mississauga, Canada. Experts completed a premeeting survey about whether items in the STROBE statement should...... should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife....
Fowlpox Virus from Backyard Poultry in Plateau State Nigeria: Isolation and Phylogeny of the P4b Gene Compared to a Vaccine Strain. Meseko, C. A.. 1. ; Shittu, I. 1. ; Bwala, D. G.. 2. ; Joannis, T. M.. 1 and Nwosuh, C. I.. 2. 1Regional Laboratory For Animal Influenza and Transboundary Animal Diseases, National Veterinary ...
Maslow, Joel N
The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. Clinical trial design for diseases with high mortality rates and/or high morbidity in the face of a global perception of immediate need and the factors that drive design in the face of a changing epidemiology are presented. Vaccines for EIDs thus present a unique paradigm to standard development precepts. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cacaci, Margherita; Lelli, Rossella Colomba
The role of the veterinarian as a public health officer is intrinsic to the history and the culture of veterinary organization in Italy. The Veterinary service being part of the Health administration since the birth of the Italian State in the XIX Century. In the second half of the last century the birth of the Italian National Health Service confirmed that the function of the Italian veterinary service was to analyze and reduce the risks for the human population connected to the relationship man-animal-environment, animal health, food safety and security. The Italian Veterinary Medicine School curricula, reflected this "model" of veterinarian as well. In the majority of countries in the world, Veterinary Services are organized within the Agriculture Administration with the main function to assure animal health and wellbeing. After the so-called "Mad-cow crisis" the awareness of the direct and essential role of veterinary services in the prevention of human illness has been officially recognized and in the third millennium the old concept of "one health" and "human-animal interface" has gained popularity worldwide.The concept of Veterinary Public Health, has evolved at International level and has incorporated the more than a century old vision of the Italian Veterinary medicine and it is defined as "the sum of the contributions to the physical, mental and social development of people through the knowledge and application of veterinary science" (WHO, Future trends in veterinary public health. Gruppo di lavoro OMS: TE, Italy, 1999, Available from: http://www.who.int/zoonoses/vph/en/ . Last visited 16 Feb 2016, 1999).On the subject of Cooperation, Sustainability and Public Health, the EXPO 2015 event and the activities of international organizations WHO, FAO and World Organization for Animal Health are refocusing at present their worldwide mandate to protect human health and the economy of both the poorest Countries and the developed countries, according to the "new
Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah
Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.
Silva, Ediane B.; Dow, Steven W.
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit
Zade, Jagdish K; Kulkarni, Prasad S; Desai, Sajjad A; Sabale, Rajendra N; Naik, Sameer P; Dhere, Rajeev M
A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis. Copyright © 2014. Published by Elsevier Ltd.
Anna P. Durbin; Stephen S. Whitehead
Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Past...
Voronin, Yegor; Snow, William
To describe and compare the diverse organizational structures and funding mechanisms applied to advance HIV preventive vaccine research and development and to help explain and inform evolving infrastructures and collaborative funding models. On the basis of models that have been tried, improved or abandoned over three decades, the field seems to have settled into a relatively stable set of diverse initiatives, each with its own organizational signature. At the same time, this set of organizations is forging cross-organizational collaborations, which promise to acquire newly emergent beneficial properties. Strong motivation to expedite HIV vaccine R&D has driven a diversity of customized and inventive organizational approaches, largely government and foundation funded. Although no one approach has proven a panacea, the field has evolved into a constellation of often overlapping organizations that complement or reinforce one another. The Global HIV Vaccine Enterprise, a responsive, rapidly evolving loose infrastructure, is an innovative collaboration to catalyze that evolution.
Marciniuk, Kristen; Taschuk, Ryan; Napper, Scott
Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.
Dilly, Marc; Read, Emma K; Baillie, Sarah
Developing competence in clinical skills is important if graduates are to provide entry-level care, but it is dependent on having had sufficient hands-on practice. Clinical skills laboratories provide opportunities for students to learn on simulators and models in a safe environment and to supplement training with animals. Interest in facilities for developing veterinary clinical skills has increased in recent years as many veterinary colleges face challenges in training their students with traditional methods alone. For the present study, we designed a survey to gather information from established veterinary clinical skills laboratories with the aim of assisting others considering opening or expanding their own facility. Data were collated from 16 veterinary colleges in North America and Europe about the uses of their laboratory, the building and associated facilities, and the staffing, budgets, equipment, and supporting learning resources. The findings indicated that having a dedicated veterinary clinical skills laboratory is a relatively new initiative and that colleges have adopted a range of approaches to implementing and running the laboratory, teaching, and assessments. Major strengths were the motivation and positive characteristics of the staff involved, providing open access and supporting self-directed learning. However, respondents widely recognized the increasing demands placed on the facility to provide more space, equipment, and staff. There is no doubt that veterinary clinical skills laboratories are on the increase and provide opportunities to enhance student learning, complement traditional training, and benefit animal welfare.
Milstien, Julie; Belgharbi, Lahouari
Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235
Full Text Available Objective: In the present study, the feasibility of a systematic record of clinical study data from marketing authorisation applications for veterinary medicinal products (VMP and benefits of the selected approach were investigated.Background: Drug registration dossiers for veterinary medicinal products contain extensive data from drug studies, which are not easily accessible to assessors.Evidentiary value: Fast access to these data including specific search tools could facilitate a meaningful use of the data and allow assessors for comparison of test and studies from different dossiers.Methods: First, pivotal test parameters and their mutual relationships were identified. Second, a data model was developed and implemented in a relational database management system, including a data entry form and various reports for database searches. Compilation of study data in the database was demonstrated using all available clinical studies involving VMPs containing the anthelmintic drug Praziquantel. By means of descriptive data analysis possibilities of data evaluation including graphical presentation were shown. Suitability of the database to support the performance of meta-analyses was tentatively validated.Results: The data model was designed to cover the specific requirements arising from study data. A total of 308 clinical studies related to 95 VMPs containing Praziquantel (single agent and combination drugs was selected for prototype testing. The relevant data extracted from these studies were appropriately structured and shown to be basically suitable for descriptive data analyses as well as for meta-analyses.Conclusion: The database-supported collection of study data would provide users with easy access to the continuously increasing pool of scientific information held by competent authorities. It enables specific data analyses. Database design allows expanding the data model to all types of studies and classes of drugs registered in veterinary
The history of parasitology and the teaching of veterinary parasitology in South Africa are reviewed briefly. Courses in veterinary parasitology are presented at the faculties of veterinary science at the University of Pretoria and the Medical University of South Africa as well as at the Pretoria Technicon. At the University of Pretoria, the three disciplines of veterinary parasitology, entomology, helminthology and protozoology, are covered in 330 core lectures; from 13 to 40% of the contact time is devoted to practical classes. Teaching veterinary parasitology is both labour intensive and costly, viz. R1700 (US$570) per student per annum. Such costs are justified by the R148.8 million (US$49.6 million) spent every year in South Africa on anthelmintics, ectoparasiticides and vaccines to control parasites. Veterinary parasitology is a dynamic subject and the curriculum must be revised regularly to incorporate new information. Because the parasite faunas are so diverse no single textbook can satisfy the requirements of the various institutions worldwide which teach the subject, with the result that extensive use is made of notes. In Australia and in Europe, ticks and tick-borne diseases are less important than they are in Africa; consequently insufficient space is devoted to them in textbooks to satisfy the requirements of the subject in African countries. Parasite control under extensive and intensive conditions is dealt with adequately at the University of Pretoria, but increasing emphasis will be given to small-scale farming systems, particularly if alternative food animals are to be kept.
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
... 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...
Avila-Calderón, Eric Daniel; Lopez-Merino, Ahidé; Sriranganathan, Nammalwar; Boyle, Stephen M; Contreras-Rodríguez, Araceli
Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge.
Bottazzi, Maria Elena; Brown, Ami Shah
This article provides an overview of the advances in product development and technology transfer of the vaccine against human hookworm, with particular emphasis on the lessons learned and the challenges of developing a vaccine in the nonprofit sector. The comprehensive approach to vaccine development established by the Human Hookworm Vaccine Initiative (HHVI) identifies key operational and technical aspects that are essential for a successful partnership with a developing country vaccine manufacturer. This article also highlights the importance of a global access roadmap to guide the vaccine development program. The advancement of new products for the control of neglected tropical diseases portends great challenges for global access, including aspects related to vaccine design, product development and manufacture, vaccine introduction and distribution, financing, knowledge dissemination and intellectual property management. With only three vaccines for neglected tropical diseases in clinical trials - hookworm, leishmaniasis and schistosomiasis - we are at the nascent stages of developing vaccines for neglected populations. Product development public-private partnerships, such as the HHVI, continue to show great promise on this front and will eventually provide significant control tools for achieving millennium development goals related to poverty reduction, as well as child and maternal health.
Marilda Carlos Vidotto
Full Text Available The vaccination with DNA is one of the most promising immunization techniques against a pathogens variety and tumors, for which the conventional methods have not been efficient. DNA vaccines are capable to induce immune humoral and cellular response, directed to lymphocytes CD4+ and CD8+, without the necessity of live microorganisms. In spite of the great potential of inducing protective immunity, the DNA vaccine not always has success. The immunity depends on several factors such as the selection of the target gene, construction of the expression vector, frequency and via of administration of the vaccine, amount of DNA, location of the antigen codified by the plasmid and age, health and species of vaccinated animals. This revision shows the development of some vaccines of DNA for diseases of interest in the veterinary and human medicine.A vacinação com DNA é uma das mais promissoras técnicas de imunização contra uma variedade de patógenos e tumores, para os quais os métodos convencionais não tem sido eficientes. Vacinas de DNA são capazes de induzir resposta imune humoral e celular, tanto para resposta de linfócitos CD4+ quanto CD8+, sem a necessidade de microrganismos vivos. Apesar do grande potencial de induzir imunidade protetora, a vacina de DNA nem sempre apresenta bons resultados. A imunidade depende de vários fatores como a seleção do gene alvo, construção do vetor de expressão, freqüência e via de administração da vacina, quantidade de DNA, localização do antígeno codificado pelo plasmídio e idade, saúde e espécies de animais vacinados. Esta revisão relata o desenvolvimento de algumas vacinas de DNA para doenças de interesse na medicina veterinária e humana.
Kraft, S.L.; Hoskinson, J.J.; Mussman, J.M.; Michaels, W.E.; Mclaughlin, R.; Gaughan, E.M.; Roush, J.K.
Three computerized multimedia programs on large and small animal veterinary orthopedic radiology were developed and implemented for the radiology curriculum as an alternative to traditional film-based laboratory learning. Programs utilized ''hot words'' (colored text words that displayed an overlaid image label that highlighted lesions) and interactive quizzes which responded appropriately to selected answers. ''Hot words'' helped students develop confidence in accurate lesion detection and the interactive quizzes transformed learning from a passive to an active process. Multiple examples were provided for reinforcement and concepts were incorporated from other clinical disciplines for curriculum integration. Programs were written using a presentation software program, Toolbook for DOS based platform, and contained radiographic images made by laser-scanning digitization. Multiple students could simultaneously access the programs through a network server. These pilot programs were implemented successfully and computerized multimedia presentation proved to be well suited to teaching radiology. Development of the programs required attention to a number of hardware, software, time and cost factors
Since eventual success depends on the vaccine's acceptability by livestock keepers, the project involves them in field-testing and assesses their willingness to pay for the vaccine. The project also ... Outputs. Studies. Developing vaccines for animals, the case of Contagious Bovine Pleuropneumonia (CBPP) in Africa. 53232.
Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.
Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun
Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.
Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim
The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.
Focus and Scope. The Tanzania Veterinary Journal (The Tropical Veterinarian) is a biannual Journal, which publishes original contribution to knowledge on Veterinary Science, Animal Science and Production, and allied sciences including new techniques and developments in Veterinary Medicine. The target readers of the ...
Milstien, Julie; Schmitt, Sarah
Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018
Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.
Mistilis, Matthew; Bommarius, Andreas S; Prausnitz, Mark R.
The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and HEPES buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane led to increased stability compared to drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for six months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain. PMID:25448542
Lairmore, Michael D; Oglesbee, Michael; Weisbrode, Steve E; Wellman, Maxey; Rosol, Thomas; Stromberg, Paul
Recent reports project a deficiency of veterinary pathologists, indicating a need to train highly qualified veterinary pathologists, particularly in academic veterinary medicine. The need to provide high-quality research training for veterinary pathologists has been recognized by the veterinary pathology training program of the Ohio State University (OSU) since its inception. The OSU program incorporates elements of both residency training and graduate education into a unified program. This review illustrates the components and structure of the training program and reflects on future challenges in training veterinary pathologists. Key elements of the OSU program include an experienced faculty, dedicated staff, and high-quality students who have a sense of common mission. The program is supported through cultural and infrastructure support. Financial compensation, limited research funding, and attractive work environments, including work-life balance, will undoubtedly continue to be forces in the marketplace for veterinary pathologists. To remain competitive and to expand the ability to train veterinary pathologists with research skills, programs must support strong faculty members, provide appropriate infrastructure support, and seek active partnerships with private industry to expand program opportunities. Shortages of trained faculty may be partially resolved by regional cooperation to share faculty expertise or through the use of communications technology to bridge distances between programs. To foster continued interest in academic careers, training programs will need to continue to evolve and respond to trainees' needs while maintaining strong allegiances to high-quality pathology training. Work-life balance, collegial environments that foster a culture of respect for veterinary pathology, and continued efforts to reach out to veterinary students to provide opportunities to learn about the diverse careers offered in veterinary pathology will pay long
Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.
Jessen, Leon Eyrich
Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...... immunity with multiple infections. Placental malaria (PM) is caused by P. falciparum sequestering in the placenta of pregnant women due to the presence of novel receptors in the placenta. An estimated 200,000 infants die a year as a result of PM. In 2004 the specific protein responsible...... and development in the field of placental malaria vaccine development....
Feng, Zhi-Xin; Wei, Yan-Na; Li, Gui-Lan; Lu, Xiao-Ming; Wan, Xiu-Feng; Pharr, G Todd; Wang, Zhan-Wei; Kong, Meng; Gan, Yuan; Bai, Fang-Fang; Liu, Mao-Jun; Xiong, Qi-Yan; Wu, Xu-Su; Shao, Guo-Qing
Mycoplasma hyopneumoniae (M. hyopneumoniae) causes a chronic respiratory disease with high morbidity and low mortality in swine, and has been presented as a major cause of growth retardation in the swine industry. Aerosol vaccination presents a needle free, high throughput, and efficient platform for vaccine delivery, and has been widely applied in poultry vaccination. However, aerosol vaccines have rarely been used in swine vaccination primarily because the long and curving respiratory track of swine presents a barrier for vaccine particle delivery. To develop an effective M. hyopneumoniae aerosol vaccine, three major barriers need to be overcome: to optimize particle size for aerosol delivery, to maintain the viability of mycoplasma cells in the vaccine, and to optimize the environmental conditions for vaccine delivery. In this study, an aerosol mycoplasma vaccine was successfully developed based on a conventional live attenuated M. hyopneumoniae vaccine. Specifically, the Pari LCD nebulizer was used to produce an aerosol vaccine particle size less than 5 μm; and a buffer with 5% glycerol was developed and optimized to prevent inactivation of M. hyopneumoniae caused by aerosolization and evaporation. Before nebulization, the room temperature and relative humidity were control to 20-25 °C and 70-75%, respectively, which helped maintain the viability of aerosol vaccine. Animal experiments demonstrated that this newly developed aerosol vaccine was effectively delivered to swine low respiratory track, being confirmed by nested-PCR, in situ hybridization and scanning electron microscope. Moreover, M. hyopneumoniae specific sIgA secretion was detected in the nasal swab samples at 14 days post-immunization. To our knowledge, this is the first report on a live M. hyopneumoniae aerosol vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.
Full Text Available Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines.
Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.
Liang, Huabin; Lee, Min; Jin, Xia
Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.
Pichichero, Michael E
The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.
Colgan, P.; Harrison, D.; Moore, W.
Under the NSW Radiation Control Act 1990, radiation apparatus used for diagnostic medical, dental and veterinary purposes will be required to become registered. The inspection required prior to registration will be conducted by a Consulting Radiation Expert who has been accredited by the Environment Protection Authority (EPA) as being competent in the field of quality assurance assessment of radiation apparatus used for diagnostic medical, dental and veterinary purposes. When regulating any activity in NSW, there is a requirement to undertake a regulatory impact statement of the proposed regulation. In addition, the introduction of any accompanying guideline requires a cost-benefit analysis. Costs may include enforcement, administrative and compliance activities. The calculation of benefit relies heavily on the improvement in apparatus performance (and hence dose reduction) that can be obtained with the introduction of a mandatory practice such as apparatus registration. This paper discusses the development of the registration guideline for NSW, including a summary of the public comments received. It further discusses the methodology and data used for the accompanying cost-benefit analysis. Information in this paper is presented in three parts: EPA field survey, cost analysis, and benefit analysis. For NSW it was estimated that the introduction of registration of these apparatus, over a two year period, would result in early replacement and repair costs (present values) to the medical industry of between $5.7 and $11.0 million, with an additional $2.5 million in EPA enforcement costs. The introduction of the proposed system of registration is expected to result in an estimated savings in quantifiable health detriment costs to NSW of between $11.8 and $17.7 million, and reduce the risk of radiation induced mortality. (authors)
Reza Pilehchian Langroudi
Full Text Available Context: The genus Clostridium, which consists of spore-forming anaerobes, can cause different diseases in domestic animals and human and some of them are serious and fatal. According to the increasing economic value of the meat and milk-producing animals, the importance of a certain number of such diseases in Iran is unquestionable. Evidence Acquisition: In Iran, and probably in other Near East countries, much attention was formerly paid to control more serious contagious diseases, such as rinderpest, anthrax, etc. resulting in the negligence of diseases such as enterotoxaemia. The epizootiological position has now changed whereby some of the contagious diseases are eradicated or are being methodically controlled.Now it is time to care about the other problems such as clostridial diseases, which threaten the health of the sheep and cattle. It is impossible to eradicate these infectious microorganisms, since they are normally found in the soil and the intestinal contents of apparently healthy animals. Therefore, it is necessary to resort to vaccination which in some cases has given encouraging results. To avoid the losses from such infections it is necessary to have the best possible vaccination information, methodically and regularity of the susceptible animals. Conclusions: This review refers to the veterinary aspects of the anaerobic clostridial diseases and vaccine development concerning the works carried out in Iran and especially at the Razi Serum and Vaccine Research Institute in the last eight decades.
Anna P. Durbin
Full Text Available Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.
Durbin, Anna P; Whitehead, Stephen S
Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.
Khamesipour, Ali; Rafati, Sima; Davoudi, Noushin; Maboudi, Fereidoun; Modabber, Farrokh
A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.
Lee, John S; Hadjipanayis, Angela G; Parker, Michael D
.... DNA vectors, live-attenuated viruses and bacteria, recombinant proteins combined with adjuvant, and viral- or bacterial-vectored vaccines have been developed as countermeasures against many potential...
Bresalier, Michael; Worboys, Michael
This paper examines the successful campaign in Britain to develop canine distemper vaccine between 1922 and 1933. The campaign mobilized disparate groups around the common cause of using modern science to save the nation's dogs from a deadly disease. Spearheaded by landed patricians associated with the country journal The Field, and funded by dog owners and associations, it relied on collaborations with veterinary professionals, government scientists, the Medical Research Council (MRC) and the commercial pharmaceutical house the Burroughs Wellcome Company (BWC). The social organization of the campaign reveals a number of important, yet previously unexplored, features of interwar science and medicine in Britain. It depended on a patronage system that drew upon a large base of influential benefactors and public subscriptions. Coordinated by the Field Distemper Fund, this system was characterized by close relationships between landed elites and their social networks with senior science administrators and researchers. Relations between experts and non-experts were crucial, with high levels of public engagement in all aspects of research and vaccine development. At the same time, experimental and commercial research supported under the campaign saw dynamic interactions between animal and human medicine, which shaped the organization of the MRC's research programme and demonstrated the value of close collaboration between veterinary and medical science, with the dog as a shared object and resource. Finally, the campaign made possible the translation of 'laboratory' findings into field conditions and commercial products. Rather than a unidirectional process, translation involved negotiations over the very boundaries of the 'laboratory' and the 'field', and what constituted a viable vaccine. This paper suggests that historians reconsider standard historical accounts of the nature of patronage, the role of animals, and the interests of landed elites in interwar British
Eric Daniel Avila-Calderón
Full Text Available Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge.
Avila-Calder?n, Eric Daniel; Lopez-Merino, Ahid?; Sriranganathan, Nammalwar; Boyle, Stephen M.; Contreras-Rodr?guez, Araceli
Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge. CONACYT CB-2011-01, 169259 SIP-IPN 20110891, 20134610 ICYTDF-IPN (Project of Investiga...
Kumar, Sanjai; Epstein, Judith E; Richie, Thomas L; Nkrumah, Francis K; Soisson, Lorraine; Carucci, Daniel J; Hoffman, Stephen L
Scientists from several organizations worldwide are working together to develop a multistage, multigene DNA-based vaccine against Plasmodium falciparum malaria. This collaborative vaccine development effort is named Multi-Stage DNA-based Malaria Vaccine Operation. An advisory board of international experts in vaccinology, malariology and field trials provides the scientific oversight to support the operation. This article discusses the rationale for the approach, underlying concepts and the pre-clinical development process, and provides a brief outline of the plans for the clinical testing of a multistage, multiantigen malaria vaccine based on DNA plasmid immunization technology.
Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A
Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.
N. R. Bergquist
Full Text Available Mounting evidence for acquired immunity to schistosomiasis in humans supports the case for immunological intervention. On the other hand, rapid reinfection poses a threat to younger age groups due to the slow maturation of natural resistance. However, rational approaches, based on advances in immunology and molecular biology, have substantially increased the odds of producing an effective vaccine. Since the parasite cannot replicate in the human host and serious morbidity generally occurs only after a relatively long period of heavy worm burden, complete protection against infection is not essential. The chances of success would increase if more than one of the various host/parasite interphases were targeted, for example reducing morbidity through decreased worm loads as well as through suppression of egg production. Several promising schistosome antigens have now reached an advanced phase of development and are currently undergoing independent confirmatory testing according to a standardized protocol. A few molecules are being contemplated for scaled-up production but, so far, only one has reached the stage of industrial manufacture and safety testing. Since schistosomiasis cannot realistically be controlled by a single approach, vaccination is envisaged to be implemented in conjunction with other means of control, notably chemotherapy.
Czerkinsky, Cecil; Holmgren, Jan
Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited knowledge regarding the properties of the gut immune system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; -lack of correlates/surrogates of mucosal immune protection; and -limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Czerkinsky, Cecil; Holmgren, Jan
Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: —limited knowledge regarding the properties of the gut immune system during early life;—lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines;—lack of correlates/surrogates of mucosal immune protection; and—limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries.There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. PMID:25964464
Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi
The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.
Coe, Jason B; Weijs, Cynthia A; Muise, Amy; Christofides, Emily; Desmarais, Serge
Social media is an increasingly common form of communication, with Facebook being the preferred social-networking site among post-secondary students. Numerous studies suggest post-secondary students practice high self-disclosure on Facebook. Research evaluating veterinary students' use of social media found a notable proportion of student-posted content deemed inappropriate. Lack of discretion in posting content can have significant repercussions for aspiring veterinary professionals, their college of study, and the veterinary profession they represent. Veterinarians-in-training at three veterinary colleges across Canada were surveyed to explore their use of and attitude toward the social networking site, Facebook. Students were invited to complete an online survey with questions relating to their knowledge of privacy in relation to using Facebook, their views on the acceptability of posting certain types of information, and their level of professional accountability online. Linear regression modeling was used to further examine factors related to veterinary students' disclosure of personal information on Facebook. Need for popularity (pFacebook. Understanding veterinary students' use of and attitudes toward social media, such as Facebook, reveals a need, and provides a basis, for developing educational programs to address online professionalism. Educators and administrators at veterinary schools may use this information to assist in developing veterinary curricula that addresses the escalating issue of online professionalism.
Full Text Available This paper illustrates and discusses the key issues of the geographical information system (GIS developed by the Unit of Veterinary Epidemiology of the Veneto region (CREV, defined according to user needs, spatial data (availability, accessibility and applicability, development, technical aspects, inter-institutional relationships, constraints and policies. GeoCREV, the support system for decision-making, was designed to integrate geographic information and veterinary laboratory data with the main aim to develop a sub-national, spatial data infrastructure (SDI for the veterinary services of the Veneto region in north-eastern Italy. Its implementation required (i collection of data and information; (ii building a geodatabase; and (iii development of a WebGIS application. Tools for the management, collection, validation and dissemination of the results (public access and limited access were developed. The modular concept facilitates the updating and development of the system according to user needs and data availability. The GIS management practices that were followed to develop the system are outlined, followed by a detailed discussion of the key elements of the GIS implementation process (data model, technical aspects, inter-institutional relationship, user dimension and institutional framework. Problems encountered in organising the non-spatial data and the future work directions are also described.
Ferrè, Nicola; Mulatti, Paolo; Mazzucato, Matteo; Lorenzetto, Monica; Trolese, Matteo; Pandolfo, Dario; Vio, Piero; Sitta, Guido; Marangon, Stefano
This paper illustrates and discusses the key issues of the geographical information system (GIS) developed by the Unit of Veterinary Epidemiology of the Veneto region (CREV), defined according to user needs, spatial data (availability, accessibility and applicability), development, technical aspects, inter-institutional relationships, constraints and policies. GeoCREV, the support system for decision-making, was designed to integrate geographic information and veterinary laboratory data with the main aim to develop a sub-national, spatial data infrastructure (SDI) for the veterinary services of the Veneto region in north-eastern Italy. Its implementation required (i) collection of data and information; (ii) building a geodatabase; and (iii) development of a WebGIS application. Tools for the management, collection, validation and dissemination of the results (public access and limited access) were developed. The modular concept facilitates the updating and development of the system according to user needs and data availability. The GIS management practices that were followed to develop the system are outlined, followed by a detailed discussion of the key elements of the GIS implementation process (data model, technical aspects, inter-institutional relationship, user dimension and institutional framework). Problems encountered in organising the non-spatial data and the future work directions are also described.
Frazzoli, C; Mantovani, A
The modern concept of zoonosis considers any detriment to the health and/or quality of human life resulting from relationships with (other) vertebrate or edible or toxic invertebrate animals. Whereas exposure to toxicants through foods of animal origin (a.o.) is a well-established issue, hereby we discuss it as novel zoonoses, from the standpoints of health implications as well as similarities and differences with classical zoonoses caused by biological agents. Novel toxicant-related zoonoses are linked with new issues in food safety, such as the environment-feed-food chain. In fact, the potential effect of the combined and repeated exposure to dietary toxicants is generally long-term and not readily discernible. Endocrine disrupting chemicals in staple foods of a.o. are discussed as a telling example of a food safety issue summing up critical points covered by the definition of sustainable development, also implicating health risks for generations to come. We suggest some critical points to implement the veterinary public health action in sustainable food safety, such as enhancement of Hazard Analysis and Critical Control Points systems for toxicological risk management. © 2010 Blackwell Verlag GmbH.
Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung; Hur, Sun Jin
This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.
Full Text Available The use of antimicrobial agents is the key risk factor for the development and spread of antimicrobial resistance. It is therefore generally recognized that data on the usage of antimicrobial agents in food-producing animals are essential for identifying and quantifying the risk of developing and spreading of antimicrobial resistance in the food-chain. According to the WHO guidelines, the Anatomical Therapeutic Chemical system for the classification of veterinary medicines (ATC-vet is widely recognized as a classification tool. The aim of this work is to analyze the list of registered veterinary medicinal products in R. Macedonia and to evaluate the quality and practical use of this list according to the ATC-vet classification in order to identify the risk of developing and spreading of antimicrobial resistance.
Shin, Min-Kyoung; Yoo, Han Sang
In veterinary vaccinology, the oral route of administration is an attractive alternative compared to the commonly used parenteral route. Yeasts have a number of properties that make them potential live delivery systems for oral vaccination purposes such as their high expression levels, their GRAS status, adjuvant properties, and post-translational modification possibilities. Consequently, yeasts have been employed for the expression of heterologous genes and for the production of therapeutic proteins. Yeast-based vaccines are reviewed with regard to their ability to express and produce antigens from pathogens for veterinary use. Many of these vaccines have been shown to elicit protective immune responses following oral immunization in animals. Ultimately, yeast-based oral vaccines may offer a potential opportunity for the development of novel ideal vaccines in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background Recommendations from the World Health Organization (WHO are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. Methods The decision-making processes for one malaria intervention and four vaccines were classified through (1 consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP and Immunization, Vaccines and Biologicals Department (IVB; (2 analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3 interviews with staff of partnerships working toward new vaccine availability; and (4 review and analyses of evidence informing key policy decisions. Case description WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib, pneumococcal conjugate vaccine (PCV, rotavirus vaccine (RV, and human papillomavirus vaccine (HPV, five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Discussion and evaluation Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and
Ahmed, S. Sohail; Black, Steve; Ulmer, Jeffrey
Summary This minireview will provide a perspective on new developments and concepts related to biomarker applications for vaccines. In the context of preventive vaccines, biomarkers have the potential to predict adverse events in select subjects due to differences in genetic make‐up/underlying medical conditions or to predict effectiveness (good versus poor response). When expanding them to therapeutic vaccines, their utility in identification of patients most likely to respond favourably (or avoid potentially negative effects of treatment) becomes self‐explanatory. Despite the progress made so far on dissection of various pathways of biological significance in humans, there is still plenty to unravel about the mysteries related to the quantitative and qualitative aspects of the human host response. This review will provide a focused overview of new concepts and developments in the field of vaccine biomarkers including (i) vaccine‐dependent signatures predicting subject response and safety, (ii) predicting therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic make‐up of the host that may modulate subject‐specific adverse events or affect the quality of immune responses, and (iv) the topic of volunteer stratification as a result of biomarker screening (e.g. for therapeutic vaccines but also potentially for preventive vaccines) or as a reflection of an effort to compare select groups (e.g. vaccinated subjects versus patients recovering from infection) to enable the discovery of clinically relevant biomarkers for preventive vaccines. PMID:21895991
Lopez, Anna Lena; Gonzales, Maria Liza Antoinette; Aldaba, Josephine G; Nair, G Balakrish
Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed.
sub-Saharan Africa. CBPP kills up to 50% of infected animals, when newly introduced into a population, and many ... animal and human diseases. While vaccines for CBPP are available, they have several ... project involves them in field testing and assesses their willingness to pay for the vaccine. The project also examines.
Jiang, Victoria; Jiang, Baoming; Tate, Jacqueline; Parashar, Umesh D; Patel, Manish M
The World Health Organization estimates that rotavirus diarrhea results in approximately half a million deaths and approximately 2.4 million hospitalizations in developing countries each year. Two live oral rotavirus vaccines, RotaTeq® (RV 5; Merck) and Rotarix® (RV 1; GlaxoSmithKline) with good efficacy against severe rotavirus disease and a reassuring safety profile could substantially impact the burden of rotavirus disease. In April 2009, WHO provided a recommendation for global introducti...
Cerny, E H; Lévy, R; Mauel, J; Mpandi, M; Mutter, M; Henzelin-Nkubana, C; Patiny, L; Tuchscherer, G; Cerny, T
Nicotine is the main culprit for dependence on tobacco-containing products, which in turn are a major etiologic factor for cardiovascular diseases and cancer. This publication describes a vaccine, which elicits antibodies against nicotine. The antibodies in the blood stream intercept the nicotine molecule on its way to its receptors and greatly diminish the nicotine influx to the brain shortly after smoking. The nicotine molecule is chemically linked to cholera toxin B as a carrier protein in order to induce antibodies. The potential to elicit antibodies after subcutaneous as well as intranasal immunization is evaluated. In order to simulate realistic conditions, nicotine pumps delivering the nicotine equivalent of 5 packages of cigarettes for 4 weeks are implanted into the mice 1 week prior to vaccination. The protective effect of the vaccine is measured 5 weeks after vaccination by comparing the influx of radiolabeled nicotine in the brains of vaccinated and non-vaccinated animals 5 min after challenge with the nicotine equivalent of 2 cigarettes. The polyclonal antibodies induced by the vaccine show a mean avidity of 1.8 x 10(7) l/Mol. Subcutaneous immunization elicits high antibody levels of the IgG class, and significant IgA antibody levels in the saliva of vaccinated mice can be found after intranasal vaccination. The protective effect also in the animals with implanted nicotine pumps is significant: less than 10% of radiolabeled nicotine found in the brains of non-vaccinated animals can be found in the brains of vaccinated animals. These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year
Sargeant, J. M.; O'Connor, A. M.; Dohoo, I. R.
and biostatisticians, many of whom hold or have held editorial positionswith relevant journals.Methods: Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 itemsof the STROBE statement should be modified and if items should be added to address unique issues relatedto observational......Background: The reporting of observational studies in veterinary research presents many challenges thatoften are not adequately addressed in published reporting guidelines.Objective: To develop an extension of the STROBE (Strengthening the Reporting of Observational Studiesin Epidemiology......) statement that addresses unique reporting requirements for observational studies inveterinary medicine related to health, production, welfare, and food safety.Design: A consensus meeting of experts was organized to develop an extension of the STROBE statementto address observational studies in veterinary...
Hemorrhagic septicemia is caused by gram-negative bacterium of Pasteurella multocida (P. multocida) strains. Most of the current vaccines against P. multocida have shortcomings. Presently, there is increasing efforts towards construction of recombinant clone for vaccine development against P. multocida. In this review an ...
ABSTRACT. Hemorrhagic septicemia is caused by gram-negative bacterium of Pasteurella multocida (P. multocida) strains. Most of the current vaccines against P. multocida have shortcomings. Presently, there is increasing efforts towards construction of recombinant clone for vaccine development against P. multocida.
Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines. Expert opinion: At present, around 13 candidate vaccines for TB are in the clinical phase of evaluation; however, there is still no substitute for the BCG vaccine. One major impediment to developing an effective vaccine is our lack of understanding of several of the mechanisms associated with infection and the immune response against TB. However, the recent implementation of an entirely new set of technological advances will facilitate the proposal of new candidates. Finally, development of a new vaccine will require a major coordination of effort in order to achieve its effective administration to the people most in need of it.
Their work has set the stage for commercial development of a sub-unit vaccine. ... The sub-unit vaccine will be cost-effective, easy to produce, and safe. How it will make a ... IDRC invites applications for the IDRC Doctoral Research Awards.
Sargeant, J. M.; O'Connor, A. M.; Dohoo, I. R.
The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies...... and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and whether items should be added to address unique issues related to observational...... studies in animal species with health, production, welfare or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine...
Crowther, Emma; Baillie, Sarah
Case-based learning (CBL) has been introduced as part of a major review of the veterinary curriculum at the University of Bristol. The initial aim was to improve integration between all first year subjects, i.e., basic science disciplines (anatomy, physiology, and biochemistry), animal management, and professional studies, while highlighting the…
He Jiang; Huang Min; Chen Hao; Wu Ling; Gao Peng; Wang Yan; Lei Qing
Irradiation technology is a new processing technology, It was widely used in food, medicines and medical supplies, chemical and other industries. In this paper, illustrated their applications in the degradation of pesticides, veterinary drugs and mycotoxins aspects residual pollution in food. Analysis of residual contaminants in food irradiation control study limitations and look forward to the prospect of food irradiation technology. (authors)
Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A
The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: email@example.com.
Petrulio, Christian A; Kaufman, Howard L
PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.
Kumar, Arun; Meldgaard, Trine Sundebo; Bertholet, Sylvie
Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses....... Frequent genetic shift and drift among influenzavirus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could...... provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly...
Jones, Ronald N; Pfaller, Michael A; Rhomberg, Paul R; Walter, Donald H
Tiamulin is a pleuromutilin derivative used in veterinary practice for the control and specific therapy of infections in swine. This report summarizes studies to establish standardized susceptibility testing methods, interpretive criteria, and reagent details for use in veterinary methods recently developed by the National Committee for Clinical Laboratory Standards (NCCLS) (standards M31-A and M37-A, NCCLS, Wayne, Pa., 1999). A total of 636 fastidious and nonfastidious animal and human pathogens were processed by using media and procedures described by the NCCLS. Tiamulin disk diffusion tests used a 30-microg disk concentration, and the proposed MIC breakpoints corresponding to levels achievable in animal target tissues (lung) were or =32 microg/ml for resistance. Correlate zone diameters for specific nonfastidious species were as follows: for Pasteurella multocida and staphylococci tested on Mueller-Hinton agar, susceptibility at > or =19 mm and resistance at or =16 mm and resistance at or =9 mm) was suggested for veterinary fastidious medium broth and enriched chocolate Mueller-Hinton agar. Absolute categorical agreement between NCCLS dilution and disk diffusion test results with these criteria ranged from 90.5 to 96.2%. Tiamulin susceptibility testing methods appear to be accurate in their categorical classification for indicated species, and their availability will allow immediate testing of animal isolates to guide therapy via appropriate levels of dosing and to monitor the development of resistance for agents in this unique class.
When graduating from veterinary school, veterinary professionals must be ready to enter the complex veterinary profession. Therefore, one of the major responsibilities of any veterinary school is to develop training programmes that support students’ competency development on the trajectory from
Wheelton, R.; McCaffery, A.
This brief article discusses radiation protection for diagnostic radiography in veterinary practices. It includes aspects such as a radiation protection adviser, personal dosimetry but in particular a Veterinary Monitoring Service, developed by the NRPB, which offers veterinary practitioners the convenience of making simple but essential measurements for themselves using photographic films contained in a 'vet pack' to determine the operating condition of their X-ray machine. (U.K.)
Johnston, Christine; Gottlieb, Sami L; Wald, Anna
Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.
Licensed live vaccines (polio, MMR) - Radiation- attenuated sporozoites - Genetically- attenuated sporozoites 2011 MHS Conference Whole Organism...Not sufficiently attenuated Seattle Biomedical , Gates Foundation, WEHI and USMMVP 2011 MHS Conference Subunit approach- RTS,S Vaccine RTS,S is...Ad Boost DNA plasmids [Prime] – Encoding malaria proteins CSP and AMA1 Adenovirus 5 ( attenuated )[Boost] – Encoding malaria proteins CSP and AMA1
Mani, Sachin; Wierzba, Thomas; Walker, Richard I
Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge-rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins). Copyright © 2016 World Health Organization
Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A
While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available The field of vaccinology was born from the observations by the fathers of vaccination, Edward Jenner and Louis Pasteur, that a permanent, positive change in the way our bodies respond to life-threatening infectious diseases can be obtained by specific challenge with the inactivated infectious agent performed in a controlled manner, avoiding the development of clinical disease upon exposure to the virulent pathogen. Many of the vaccines still in use today were developed on an empirical basis, essentially following the paradigm established by Pasteur, “isolate, inactivate, and inject” the disease-causing microorganism, and are capable of eliciting uniform, long-term immune memory responses that constitute the key to their proven efficacy. However, vaccines for pathogens considered as priority targets of public health concern are still lacking. The literature tends to focus more often on vaccine research problems associated with specific pathogens, but it is increasingly clear that there are common bottlenecks in vaccine research, which need to be solved in order to advance the development of the field as a whole. As part of a group of articles, the objective of the present report is to pinpoint these bottlenecks, exploring the literature for common problems and solutions in vaccine research applied to different situations. Our goal is to stimulate brainstorming among specialists of different fields related to vaccine research and development. Here, we briefly summarize the topics we intend to deal with in this discussion.
Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith
Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.
This paper discusses the movement toward self-sufficiency in vaccine supply in developing countries (and countries in transition to new economic and political systems) and explains special supply concerns about vaccine as a product class. It traces some history of donor support and programmes aimed at self-financing, then continues with a discussion about self-sufficiency in terms of institutional capacity building. A number of deficiencies commonly found in vaccine procurement and supply in low- and middle-income countries are characterized, and institutional strengthening with procurement technical assistance is described. The paper also provides information about a vaccine procurement manual being developed by the United States Agency for International Development (USAID) and the World Health Organization (WHO) for use in this environment. Two brief case studies are included to illustrate the spectrum of existing capabilities and different approaches to technical assistance aimed at developing or improving vaccine procurement capability. In conclusion, the paper discusses the special nature of vaccine and issues surrounding potential integration and decentralization of vaccine supply systems as part of health sector reform.
Full Text Available Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV serotypes 1–4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector control the only method of prevention. A particular challenge with DENV is that a successful vaccine has to be effective against all four serotypes without predisposing for antibody-mediated enhanced disease. In this review, we discuss the current lead vaccine candidates in clinical trials, as well as some second-generation vaccine candidates undergoing preclinical evaluation. In addition, we discuss DENV epidemiology, clinical disease and strategies used for Flavivirus antivirals in the past, the development of new DENV therapeutics, and their potential usefulness for prophylaxis and treatment.Keywords: tetravalent dengue vaccine, live attenuated vaccine, purified inactivated vaccine, DNA vaccine, antibody-dependent enhancement, antivirals
Mohan, Teena; Verma, Priyanka; Rao, D Nageswara
The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.
Full Text Available Infectious bronchitis (IB is an acute highly contagious viral respiratory disease of poultry caused by coronavirus. The disease causes high mortality in young chicks, reduce body weight gain in broilers and remarkable drop in egg production. IB can only be controlled by vaccination, but due to the antigenic variation among serotypes of IB viruses, the effective IB vaccine should be prepared from local isolates. The aim of this research is to develop inactivated IB vaccine derived from local IB isolates. Local isolates of IB viruses designated as I-37, I-269 and PTS-III were propagated respectively in specific pathogen free (SPF chicken eggs, the viruses then were inactivated by formaline at final concentration of 1:1,000. Subsequently, the inactivated viruses were mixed and emulsified in oil emulsion adjuvant with sorbitant mono-oleic as an emulsifier. The vaccine then was tested for its safety, potency and efficacy in broiler chickens. Birds inoculated twice with a two-week interval by inactivated vaccine did not show any adverse reaction, either systemic or local reaction. The inoculated birds developed antibody responses with high titre, while antibody of the control birds remain negative. In addition, efficacy test which was conducted in broilers demonstrated that birds vaccinated by live-commercial vaccine and boosted three weeks later by Balitvet inactivated vaccine showed high level of antibody production which provided high level of protection against challenged virus (76% against I-37, 92% against I-269 and 68% against PTS-III challenge viruses. From this study, it can be concluded that inactivated local IB vaccine is considered to be safe, potent and efficacious. The vaccine stimulates high titre of antibody responses, which provide high level of protection against challenged viruses.
Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.
Milstien, Julie B; Kaddar, Miloud; Kieny, Marie Paule
Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.
Isabel N. Kantor
Full Text Available Dengue (DENV, zika (ZIKV and chikungunya (CHIKV, three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.
Kantor, Isabel N
Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.
Kimura, Kiminori; Kohara, Michinori
Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.
Apr 6, 2018 ... Home · Resources · Publications. Development of 2 multivalent RVF vaccines for improved uptake in cattle and in small ruminants ... concern in recent years, with an increasing number of human cases recorded in Mauritania, ...
The Nanotechnology Characterization Laboratory (NCL) is collaborating with the Army to develop a candidate vaccine against botulism. Under a collaboration agreement between the National Cancer Institute and the U.S. Army Medical Research Institute of
Tissera, Marion S; Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L; Lyras, Dena; Kirkwood, Carl D; Buttery, Jim P
Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.
Kaatari, S.; Turaga, P.; Wiens, G.
This document is the executive summary and background review for the final report of ''Development of a Vaccine for Bacterial Kidney Disease in Salmon''. A description of the disease is provided, with microbiological characterization of the infective agent. A brief discussion of attempts to eradicate the disease is included. Recent progress in vaccine development and attempts to control the disease through pharmacological means are described, along with potential ways to break the cycle of infection. 80 refs
Xu, Zhi-Yi; Wang, Xuan-Yi
Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971
Gerretsen, Hannah E; Sande, Charles J
2017 will mark the 60 th anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Willis, Natalie; Hill, Sophie; Kaufman, Jessica; Lewin, Simon; Kis-Rigo, John; De Castro Freire, Sara Bensaude; Bosch-Capblanch, Xavier; Glenton, Claire; Lin, Vivian; Robinson, Priscilla; Wiysonge, Charles S
Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality. However, childhood vaccination coverage remains sub-optimal in many settings. While communication is a key feature of vaccination programmes, we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage. Developing a classification system (taxonomy) organised into conceptually similar categories will aid in: understanding the relationships between different types of communication interventions; facilitating conceptual mapping of these interventions; clarifying the key purposes and features of interventions to aid implementation and evaluation; and identifying areas where evidence is strong and where there are gaps. This paper reports on the development of the 'Communicate to vaccinate' taxonomy. The taxonomy was developed in two stages. Stage 1 included: 1) forming an advisory group; 2) searching for descriptions of interventions in trials (CENTRAL database) and general health literature (Medline); 3) developing a sampling strategy; 4) screening the search results; 5) developing a data extraction form; and 6) extracting intervention data. Stage 2 included: 1) grouping the interventions according to purpose; 2) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback; 3) conducting a targeted search of grey literature to supplement the taxonomy; 4) finalising the taxonomy based on the input provided. The taxonomy includes seven main categories of communication interventions: inform or educate, remind or recall, teach skills, provide support, facilitate decision making, enable communication and enhance community ownership. These categories are broken down into 43 intervention types across three target groups: parents or soon-to-be-parents; communities, community
Hughes, K L
The geographic isolation of Australasia has played a significant role in preventing the introduction of exotic diseases or in limiting the spread of many diseases which entered after settlement. Some infections such as psoroptic mange, tuberculosis and brucellosis became widely dispersed and some were ultimately to require novel methods to curtail them, e.g. greater use of rail and road transportation to convey stock, improved methods to locate and muster livestock in bush terrain (helicopters), improved diagnostic tests and the introduction of effective methods for tracing diseases found at abattoirs to the farms of origin. From the 1860s to the 1880s, there were such high mortalities from anthrax in Australia that a business syndicate associated with the Pasteur Institute established a laboratory in Sydney to produce anthrax vaccine from 1890 to 1898. The two-dose vaccine developed by Pasteur was unable to compete with a single dose spore vaccine later pioneered locally by Gunn and McGarvie-Smith. The most important achievements in veterinary public health in Australasia have been the successful eradication of brucellosis, the virtual eradication of hydatid disease in New Zealand and Tasmania, the substantial progress made in the eradication of tuberculosis from all but small regions of Australasia, and the development of a commercial vaccine to prevent Q fever in humans.
Heppell, Joël; Lorenzen, Niels; Armstrong, Neil K.
Disease control is one of the major concerns in the aquaculture industry. However, there are no vaccines available for the prevention of many piscine infectious diseases, especially those of viral and parasitic origin. DNA-based vaccination could circumvent several problems associated with tradit......Disease control is one of the major concerns in the aquaculture industry. However, there are no vaccines available for the prevention of many piscine infectious diseases, especially those of viral and parasitic origin. DNA-based vaccination could circumvent several problems associated...... with traditional methods of immunization, but little is known on its efficacy in fish. The luciferase and lacZ reporter genes were used to characterize expression of plasmid-encoded genes in rainbow trout and zebra fish injected intramuscularly. For a given dose of DNA, the luciferase activity was higher in fish...... than in mouse muscle. The enzyme activity in fish peaked with 1 μg of DNA and remained constant for over 12 weeks, but it was not limited to the injected muscle since luciferase activity was also detected in the gills. Thin sections of rainbow trout muscle injected with the lacZ reporter gene showed...
Kirshin, V.A.; Belov, A.D.; Budarkov, V.A.; Prochazka, Z.
The monograph summarizes the authors' experience and data from Soviet and foreign scientific literature. It consists of the following chapters: radioactive sources; utilization of ionizing radiation and radioactive isotopes; biological effects of ionizing radiation; radiation sickness in animals; combined post-irradiation syndromes; prophylaxis of radiation injury; therapy of irradiated animals; and veterinary radiation hygiene control of the environment, fodder, animals and animal products. (P.A.)
Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra
Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Kuhlmann-Gottke, Johanna; Duchow, Karin
At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.
Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A
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...
Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.
Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426
Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L
Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.
Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika
The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.
Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il
Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.
Gruber, Joann F; Hille, Darcy A; Liu, G Frank; Kaplan, Susan S; Nelson, Micki; Goveia, Michelle G; Mast, T Christopher
Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries. An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status. African children receiving the first dose at efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries. Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.
Kustritz, Margaret V Root; Nault, André J
Veterinary education has traditionally focused on clinical skills. Success as a practicing veterinarian, however, also depends on good communication skills, emotional intelligence, and other "soft" skills that can lead to greater employee and employer satisfaction and increased practice revenue. The University of Minnesota has approached this curricular need by convening a task force and creating a series of courses aimed at improving leadership skills, teamwork, and verbal and written communication; managing conflict; and understanding ethics and personal finance. This article describes the evolution and structure of these soft-skill classes and the challenges in securing faculty and student buy-in essential for success.
Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P
Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Mackiewicz, Jacek; Mackiewicz, Andrzej
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.
Lydia M. Roberts
Full Text Available Francisella tularensis is an intracellular bacterium that causes the disease tularemia. There are several subspecies of F. tularensis whose ability to cause disease varies in humans. The most virulent subspecies, tularensis, is a Tier One Select Agent and a potential bioweapon. Although considerable effort has made to generate efficacious tularemia vaccines, to date none have been licensed for use in the United States. Despite the lack of a tularemia vaccine, we have learned a great deal about the adaptive immune response the underlies protective immunity. Herein, we detail the animal models commonly used to study tularemia and their recapitulation of human disease, the field's current understanding of vaccine-mediated protection, and discuss the challenges associated with new vaccine development.
Paulsen, Lynn Mulcahy
A one-semester, two-credit course is described that was developed cooperatively by the colleges of pharmacy and veterinary medicine at Washington State University to help resolve an acute shortage of clinical pharmacologists in veterinary medicine and veterinary medical education. Course procedures, content, and evaluation are outlined (MSE)
Roest, H.I.J.; Engelsma, M.Y.; Weesendorp, E.; Bossers, A.; Elbers, A.R.W.
In veterinary molecular diagnostics, samples originating from animals are tested. Developments in the farm animals sector and in our societal attitude towards pet animals have resulted in an increased demand for fast and reliable diagnostic techniques. Molecular diagnostics perfectly matches this
Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong
Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.
Gelberg, H B; Gelberg, S
It is important for veterinary administrators to apply knowledge bases from other fields to their own unique administrative needs. For example, although some resources are written for business managers, the discussions of four key management competency areas, guidelines for mastering these skills, organizational assessment tools, and other self-help tools may provide interesting food-for-thought for veterinary administrators.(76) In developing their own administrative styles, administrators should seek to apply those principles that seem to intuitively fit with their personal research styles, work situations, managerial styles, administrative preferences, and unique organizational culture. Through strengthening their liaisons with community and university business programs, counseling agencies, employee assistance programs, and psychology researchers, administrators can continue to be exposed to and benefit from new paradigms for consideration in veterinary medical environments. Through these liaisons, the unique needs of veterinary medical environments are also communicated to individuals within the fields of psychology and business, thus stimulating new research that specifically targets veterinary medical environment leadership issues. Each field has unique contributions to help veterinary administrators work toward creating veterinary medical environments that are creative, energetic, visionary, pragmatic, and highly marketable in order to help administrators recruit and nurture the best and brightest veterinary researchers, teachers, and clinicians.
Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas
Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...
Full Text Available Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.Methods: Scientific databases, including MEDLINE (via PubMed and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.
Cameron, Caroline E; Lukehart, Sheila A
Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community's accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding
Over the past two decades pharmaceutical industry interest in the development of vaccines against infectious diseases has grown. At the same time various partnerships and mechanisms have been established in order to reconcile the interests of private industry with the needs of public health systems
Full Text Available Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression, are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.
Nogales, Aitor; Martínez-Sobrido, Luis
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504
Permar, Sallie R.; Plotkin, Stanley A.
ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice. PMID:29046308
Amith, Muhammad; Gong, Yang; Cunningham, Rachel; Boom, Julie; Tao, Cui
To construct a comprehensive vaccine information ontology that can support personal health information applications using patient-consumer lexicon, and lead to outcomes that can improve patient education. The authors composed the Vaccine Information Statement Ontology (VISO) using the web ontology language (OWL). We started with 6 Vaccine Information Statement (VIS) documents collected from the Centers for Disease Control and Prevention (CDC) website. Important and relevant selections from the documents were recorded, and knowledge triples were derived. Based on the collection of knowledge triples, the meta-level formalization of the vaccine information domain was developed. Relevant instances and their relationships were created to represent vaccine domain knowledge. The initial iteration of the VISO was realized, based on the 6 Vaccine Information Statements and coded into OWL2 with Protégé. The ontology consisted of 132 concepts (classes and subclasses) with 33 types of relationships between the concepts. The total number of instances from classes totaled at 460, along with 429 knowledge triples in total. Semiotic-based metric scoring was applied to evaluate quality of the ontology.
Kinnison, Tierney; Lumbis, Rachel; Orpet, Hilary; Welsh, Perdi; Gregory, Sue; Baillie, Sarah
Interprofessional education (IPE) has received little attention in veterinary education even though members of the veterinary and nursing professions work closely together. The present study investigates veterinary and veterinary nursing students' and practitioners' experiences with interprofessional issues and the potential benefits of IPE. Based on stakeholder consultations, two teaching interventions were modified or developed for use with veterinary and veterinary nursing students: Talking Walls, which aimed to increase individuals' understanding of each other's roles, and an Emergency-Case Role-Play Scenario, which aimed to improve teamwork. These interventions were piloted with volunteer veterinary and veterinary nursing students who were recruited through convenience sampling. A questionnaire (the Readiness for Interprofessional Learning Scale [RIPLS]) was modified for use in veterinary education and used to investigate changes in attitudes toward IPE over time (pre-intervention, immediately post-intervention, and four to five months afterward). The results showed an immediate and significant positive change in attitude after the intervention, highlighting the students' willingness to learn collaboratively, their ability to recognize the benefits of IPE, a decreased sense of professional isolation, and reduced hierarchical views. Although nearly half of the students felt concerned about learning with students from another profession before the intervention, the majority (97%) enjoyed learning together. However, the positive change in attitude was not evident four to five months after the intervention, though attitudes remained above pre-intervention levels. The results of the pilot study were encouraging and emphasize the relevance and importance of veterinary IPE as well as the need for further investigation to explore methods of sustaining a change in attitude over time.
Harry L. T. Mobley
Full Text Available Urinary tract infection (UTI is the second most common infection in humans after those involving the respiratory tract. This results not only in huge annual economic costs, but in decreased workforce productivity and high patient morbidity. Most infections are caused by uropathogenic Escherichia coli (UPEC. Antibiotic treatment is generally effective for eradication of the infecting strain; however, documentation of increasing antibiotic resistance, allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent recurrent infections represent significant barriers to treatment. As a result, approaches to prevent UTI such as vaccination represent a gap that must be addressed. Our laboratory has made progress toward development of a preventive vaccine against UPEC. The long-term research goal is to prevent UTIs in women with recurrent UTIs. Our objective has been to identify the optimal combination of protective antigens for inclusion in an effective UTI vaccine, optimal adjuvant, optimal dose, and optimal route of delivery. We hypothesized that a multi-subunit vaccine elicits antibody that protects against experimental challenge with UPEC strains. We have systematically identified four antigens that can individually protect experimentally infected mice from colonization of the bladder and/or kidneys by UPEC when administered intranasally with cholera toxin (CT as an adjuvant. To advance the vaccine for utility in humans, we will group the individual antigens, all associated with iron acquisition (IreA, Hma, IutA, FyuA, into an effective combination to establish a multi-subunit vaccine. We demonstrated for all four vaccine antigens that antigen-specific serum IgG represents a strong correlate of protection in vaccinated mice. High antibody titers correlate with low colony forming units (CFUs of UPEC following transurethral challenge of vaccinated mice. However, the contribution of cell-mediated immunity cannot
Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng
The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.
¹Department of Veterinary Anatomy, Faculty of Veterinary Medicine, ABU Zaria, Nigeria, ²Department of. Veterinary Physiology ... dogs, AGRs have a highly sensitive sense of smell. The rats ..... Gonadal Axis and thyroid Activity in. Male rats.
Schoenfeld-Tacher, Regina M; Kogan, Lori R
Given the unique nature of programs in professional veterinary medicine (PVM), the increasing numbers of students requesting accommodations for emotional support animals (ESAs) in higher education settings is of growing interest to student affairs and administrative staff in PVM settings. Since the legislation pertaining to this type of support animal differs from the laws governing disability service animals, colleges and universities now need to develop new policies and guidelines. Representatives from a sample of 28 PVM programs completed a survey about the prevalence of student requests for ESAs and service animals. PVM associate deans for academic affairs also reported their perceptions of this issue and the challenges these requests might pose within veterinary teaching laboratories and patient treatment areas. Responses indicated that approximately one third of PVM programs have received requests for ESAs (32.1%) in the last 2 years, 17.9% have had requests for psychiatric service animals, and 17.9% for other types of service animals. Despite this, most associate deans reported not having or not being aware of university or college policies pertaining to these issues. Most associate deans are interested in learning more about this topic. This paper provides general recommendations for establishing university or PVM program policies.
Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.
Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith
Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.
Rusnak, Janice M; Smith, Leonard A
Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.
Full Text Available Graham J Belsham, Anette Bøtner National Veterinary Institute, Technical University of Denmark, Kalvehave, Denmark Abstract: Foot-and-mouth disease remains one of the world's most economically important diseases of livestock. It is caused by foot-and-mouth disease virus, a member of the picornavirus family. The virus replicates very rapidly and can be efficiently transmitted between hosts by a variety of routes. The disease has been effectively controlled in some parts of the world but remains endemic in many others, thus there is a constant risk of introduction of the disease into areas that are normally free of foot-and-mouth disease with potentially huge economic consequences. To reduce the need for large-scale culling of infected, and potentially infected, animals there has been significant effort to develop new vaccines against this disease which avoid some, or all, of the deficiencies of current vaccines. A major focus has been on the use of systems that express the structural proteins of the virus that self-assemble to generate “empty capsid” particles which share many features with the intact virus but lack the ribonucleic acid genome and are therefore non-infectious. Such particles can be “designed” to improve their stability or modify their antigenicity and can be produced without “high containment” facilities. The development and use of such improved vaccines should assist in the global efforts to control this important disease. Keywords: picornavirus, diagnostic assays, virus structure, infection, immune responses
Computers have been used to automate complex and repetitive tasks in veterinary hospitals since the 1960s. Early systems were expensive, but their use was justified because they performed jobs which would have been impossible or which would have required greater resources in terms of time and personnel had they been performed by other methods. Systems found in most veterinary hospitals today are less costly, magnitudes more capable, and often underused. Modern multitasking operating systems and graphical interfaces bring many opportunities for automation. Commercial and custom programs developed and used in a typical multidoctor mixed species veterinary practice are described.
Full Text Available Henricus LBM (Eric Klaasen,1 Ben Adler2 1Global Companion Animals Research and Development, Merck Sharp and Dohme Animal Health, Boxmeer, the Netherlands; 2Department of Microbiology, Monash University, Clayton, VIC, Australia Abstract: Leptospirosis is a global infection of humans and animals caused by pathogenic Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from wild and domestic animals. It is also a significant cause of morbidity, mortality, and economic loss in production and companion animals. Leptospirosis in dogs is prevalent worldwide and as well as a cause of canine disease, it presents a zoonotic risk to human contacts. Canine leptospirosis does not differ greatly from the syndromes seen in other animal species, with hepatic, renal, and pulmonary involvement being the main manifestations. While the pathogenesis of disease is well documented at the whole animal level, the cellular and molecular basis remains obscure. Killed, whole-cell bacterin vaccines are licensed worldwide and have not changed greatly over the past several decades. Vaccine-induced immunity is restricted to serologically related serovars and is generally short-lived, necessitating annual revaccination. The appearance of new serovars as causes of canine leptospirosis requires constant epidemiological surveillance and tailoring of vaccines to cover emerging serovars. At the present time, there is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable future. Keywords: canine leptospirosis, vaccines, diagnosis, epidemiology, pathogenesis
Stephanie F James
Full Text Available Objective: To describe an elective course on immunology and vaccines for pharmacy students that extends beyond basic immunization training. Design: A three credit-hour Immunology and Vaccines elective was developed and taught by an immunologist, policy research expert, and pharmacist. The learning objectives of the course included: understanding how the immune system works with vaccines to provide protection against infectious diseases, the history and policies involved in immunization practice, and how to counsel the vaccine hesitant individual. Classes were conducted using a variety of formats; group projects, lectures, films, literature reviews and guest speakers. An end-of-course evaluation was used to gauge student opinion on course value. Students were evaluated by four exams and a final group presentation. Conclusion: Students indicated that this course was valuable to their future pharmacy careers and provided insight into why people choose not to vaccinate and how they could use the course insight to properly educate such individuals. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties Type: Note
Gera, Prachi; Gupta, Ankit; Verma, Priyanka; Singh, Joginder; Gupta, Jeena
With the increasing rate of Ebola virus appearance, with multiple natural outbreaks of Ebola hemorrhagic fever, it is worthy of consideration as bioweapon by anti-national groups. Further, with the non-availability of the vaccines against Ebola virus, concerns about the public health emerge. In this regard, this review summarizes the structure, genetics and potential of Ebola virus to be used as a bioweapon. We highlight the recent advances in the treatment strategies and vaccine development against Ebola virus. The understanding of these aspects might lead to effective treatment practices which can be applied during the future outbreaks of Ebola.
Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub
Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.
Zhuang, Xiaodong; Bicknell, Roy
A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.
Bellver Capella, Vincente
Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.
Syaifudin, M.; Tetriana, D.; Darlina; Nurhayati, S.
Malaria, a plasmodial disease, causes more than one million deaths per year and has a significant public health impact. Improved access to prompt treatment with effective antimalarial drugs need to be conducted for prevention of infection in high risk groups. However, the parasite as causal agent has exhibited a potential danger of wide-spread resistances. This warning has directed attention to the study of alternative methods of protection against the disease, among them is to do the immunization. A deeper understanding of the nature and regulation of protective immune mechanisms against this parasite will facilitate the development of much needed vaccines. Developing a malaria vaccine remains an enormous scientific, technical, and financial challenge. Currently a vaccine is not fully available. Among the practical applications of radiobiological techniques that may be of considerable interest for public health is the use of ionizing radiation in the preparation of vaccines. Convincing data were reported that sporozoites of Plasmodium berghei irradiated with X- or gamma-rays, provide an antigenic stimulus effective to induce a protective immune response in mice and rats against subsequent sporozoite infection. Irradiated parasites are better immunogens than killed ones and although non-infective they are still metabolically active, as shown by continued protein and nucleic acid synthesis. There is a substantial number of data from human studies demonstrating that sporozoites attenuated by radiation are potent inducer of protective immunity and that they are safe and do not give rise to the asexual erythrocytic infections that cause malaria. This vaccine is relatively inexpensive to produce, easy to store, and transportable without refrigeration. A long-term effort and commitment to providing resources must be maintained and increased to achieve the goal of a malaria vaccine candidate where ionizing radiation as a tool to prepare is seemingly feasible. (author)
Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.
By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed
Lee, John S; Hadjipanayis, Angela G; Parker, Michael D
... agents of bioterrorism or biowarfare. The use of viruses, for example adenovirus, vaccinia virus, and Venezuelan equine encephalitis virus, as vaccine-vectors has enabled researchers to develop effective means for countering the threat of bioterrorism and biowarfare. An overview of the different viral vectors and the threats they counter will be discussed.
State-of-the-art technologies developed in two laboratories will be combined: nanotechnology and a new adjuvant. These approaches will allow simple production of nanoparticles that do not require any special containment, as opposed to traditional vaccines produced in embryonated eggs. This project is a collaboration ...
Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha
DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.
Development of myiasis vaccine: In vitro detection of immunoprotective responses of peritrophic membrane protein, first instar larva Ll supernatant and pellet antigen of fly Chrysomyia bezziana in sheep
Full Text Available Myiasis control by means of individual treatment of animals which are mainly rised extensively is time consumed and expensive. The alternative way to control this disease by vaccination is considered effective and economically accepted. However the expected vaccine is now still being developed under a collaborative project between CSIRO, Inter-University Centre on Biotechnology-ITB and Research Institute for Veterinary Science and funded by ACIAR. There are several antigens have been identified as vaccine candidates and an in vitro bioassay technique has been developed for assessing the immunoresponses of vaccine in sheep. Three antigens were used for vaccines in this study, these included protein peritrophic membrane (PM, soluble extract (SE and pellet extract (PE of 1st instar larvae of Chrysomya bezziana. Twenty four experimental sheep were divided into 4 groups of 6 animals, 3 groups of animals were injected with PM, SE and PE vaccines with the dose rate of 0.5 g PM/head, 0.8 g PE/head and 4.2 ml LE/head respectively, and the other one group was injected with 4 ml PBS/head as a control group. Vaccination with the same dose was repeated 4 weeks after the 1st vaccination as a booster, and 2 weeks after the booster the sheep were challenged with live larvae, 3 days after challenge animals were killed. Sera were collected at the day of vaccination, 4 weeks after vaccination, 2 weeks after booster, and 3 days after challenge. An in vitro bioassay technique was conducted by culturing 1st instar larvae on five media containing sera collected from each experimental animal. The effects of sera on cultivated larvae were assessed by means of larval weight and larval mortality rate. The results indicated that the growth rate and survival of cultivated larvae in media containing anti-PM sera were significantly lower (P<0.01 compared to the larvae cultivated on media with sera on the day of vaccination. The larval weight depression by anti- PM sera
The Ebola epidemic that occurred in West Africa between 2013-2016 significantly accelerated the research and development of Ebola vaccines. Few dozens of clinical trials have been recently conducted leading to opportunities to test several new vaccine candidates. Other vaccines are still in early development phases (table 1). This paper provides an overview of the new developments in that area.
Mansilla, Florencia C; Capozzo, Alejandra V
Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of reproductive loss in cattle and neuromuscular disease in dogs. Bovine neosporosis has a great economic impact in both meat and dairy industries, related to abortion, premature culling and reduced milk yields. Although many efforts have been made to restrain bovine neosporosis, there are still no efficacious control methods. Many vaccine-development studies focused in the apicomplexan proteins involved in the adhesion and invasion of the host cell. Among these proteins, profilins have recently emerged as potential vaccine antigens or even adjuvant candidates for several diseases caused by apicomplexan parasites. Profilins bind Toll-like receptors 11 and 12 initiating MyD88 signaling, that triggers IL-12 and IFN-γ production, which may promote protection against infection. Here we summarized the state-of-the-art of novel vaccine development based on apicomplexan profilins applied as antigens or adjuvants, and delved into recent advances on N. caninum vaccines using profilin in the mouse model and in cattle. Copyright © 2017 Elsevier Inc. All rights reserved.
Nyamathi, Adeline M; Fahey, John L; Sands, Heather; Casillas, Adrian M
Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.
Weese, J Scott; Jack, Douglas C
Needlestick injuries are an inherent risk of handling needles during the course of veterinary practice. While significant effort has been expended to reduce needlestick injuries in human medicine, a relatively lax approach seems to be prevalent in veterinary medicine. It appears that needlestick injuries are very common among veterinary personnel and that serious adverse effects, while uncommon, do occur. Clients may also receive injuries in clinics during the course of animal restraint, and at home following prescription of injectable medications or fluids. Because of occupational health, personal health, and liability concerns, veterinary practices should review the measures they are taking to reduce the likelihood of needlestick injuries and develop written needlestick injury avoidance protocols.
Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong
China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843
Wiegers, Ann L
Third-party accreditation is a valuable tool to demonstrate a laboratory's competence to conduct testing. Accreditation, internationally and in the United States, has been discussed previously. However, accreditation is only I part of establishing data credibility. A validated test method is the first component of a valid measurement system. Validation is defined as confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. The international and national standard ISO/IEC 17025 recognizes the importance of validated methods and requires that laboratory-developed methods or methods adopted by the laboratory be appropriate for the intended use. Validated methods are therefore required and their use agreed to by the client (i.e., end users of the test results such as veterinarians, animal health programs, and owners). ISO/IEC 17025 also requires that the introduction of methods developed by the laboratory for its own use be a planned activity conducted by qualified personnel with adequate resources. This article discusses considerations and recommendations for the conduct of veterinary diagnostic test method development, validation, evaluation, approval, and transfer to the user laboratory in the ISO/IEC 17025 environment. These recommendations are based on those of nationally and internationally accepted standards and guidelines, as well as those of reputable and experienced technical bodies. They are also based on the author's experience in the evaluation of method development and transfer projects, validation data, and the implementation of quality management systems in the area of method development.
Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.
Kaslow, David C
Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.
...] The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop AGENCY: Food and... Evaluation of Next-Generation Smallpox Vaccines.'' The purpose of the public workshop is to identify and discuss the key issues related to the development and evaluation of next-generation smallpox vaccines. The...
Cunningham, Anthony L; Garçon, Nathalie; Leo, Oberdan; Friedland, Leonard R; Strugnell, Richard; Laupèze, Béatrice; Doherty, Mark; Stern, Peter
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning: 1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age. 2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection. 3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production. 4. Vaccine preclinical
Despite of growing oncology pipeline, cancer vaccines contribute only to a minor share of total oncology-attributed revenues. This is mainly because of a limited number of approved products and limited sales from products approved under compassionate or via early access entry in smaller and less developed markets. However revenue contribution from these products is extremely limited and it remains to be established whether developers are breaking even or achieving profitability with existing sales. Cancer vaccine field is well recognized for high development costs and risks, low historical rates of investment return and high probability of failures arising in ventures, partnerships and alliances. The cost of reimbursement for new oncology agents is not universally acceptable to payers limiting the potential for a global expansion, market access and reducing probability of commercial success. In addition, the innovation in cancer immunotherapy is currently focused in small and mid-size biotech companies and academic institutions struggling for investment. Existing R&D innovation models are deemed unsustainable in current "value-for-money" oriented healthcare environment. New business models should be much more open to collaborative, networked and federated styles, which could help to outreach global, markets and increase cost-efficiencies across an entire value chain. Lessons learned from some developing countries and especially from South Korea illustrate that further growth of cancer vaccine industry will depends not only on new business models but also will heavily rely on regional support and initiatives from different bodies, such as governments, payers and regulatory bodies.
Gavin C. Bowick
Full Text Available Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.
Ruch-Gallie, R; Moroff, S; Lappin, M R
Canine adenovirus 2, parainfluenza, and Bordetella bronchiseptica cause respiratory disease in dogs, and each has a modified live intranasal vaccine available. Molecular diagnostic assays to amplify specific nucleic acids are available for each of these agents. If positive molecular diagnostic assay results are common after vaccination, the positive predictive value of the diagnostic assays for disease would be decreased. To determine the impact of administration of commercially available modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza vaccine has on the results of a commercially available PCR panel. Eight puppies from a research breeding facility negative for these pathogens. Blinded prospective pilot study. Puppies were vaccinated with a single dose of modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza and parenteral dose of adenovirus 2, canine distemper virus, and parvovirus. Nasal and pharyngeal swabs were collected on multiple days and submitted for PCR assay. Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination. Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild-type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Full Text Available Diarrheal diseases are one of the major causes of mortality among children under five years old and intestinal pathogenic Escherichia coli (InPEC plays a role as one of the large causative groups of these infections worldwide. InPECs contribute significantly to the burden of intestinal diseases, which are a critical issue in low- and middle-income countries (Asia, Africa and Latin America. Intestinal pathotypes such as enteropathogenic E. coli (EPEC and enterotoxigenic E. coli (ETEC are mainly endemic in developing countries, while ETEC strains are the major cause of diarrhea in travelers to these countries. On the other hand, enterohemorrhagic E. coli (EHEC are the cause of large outbreaks around the world, mainly affecting developed countries and responsible for not only diarrheal disease but also severe clinical complications like hemorrhagic colitis and hemolytic uremic syndrome (HUS. Overall, the emergence of antibiotic resistant strains, the annual cost increase in the health care system, the high incidence of traveler diarrhea and the increased number of HUS episodes have raised the need for effective preventive treatments. Although the use of antibiotics is still important in treating such infections, non-antibiotic strategies are either a crucial option to limit the increase in antibiotic resistant strains or absolutely necessary for diseases such as those caused by EHEC infections, for which antibiotic therapies are not recommended. Among non-antibiotic therapies, vaccine development is a strategy of choice but, to date, there is no effective licensed vaccine against InPEC infections. For several years, there has been a sustained effort to identify efficacious vaccine candidates able to reduce the burden of diarrheal disease. The aim of this review is to summarize recent milestones and insights in vaccine development against InPECs.
Shigella species Dengue Salmonella Filoviruses Listeria monocytogenes Ebola Campylobacter jejuni Marburg Yersinia entercolitica Viruses (Caliciviruses...Orthopoxvirus genus containing the monkey - J.S. Lee et al. / Advanced Drug Delivery Reviews 57 (2005) 1293–1314 1297 Approved for public release. Distribution...four monkeys vaccinated with V-LSGPC produced antibodies specific for LSV. After challenge, the four monkeys developed a febrile illness with low
An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.
Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.
Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia
The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bonnie M Slike
Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.
Al-Awadhi, Aydah; Murray, James Lee; Ibrahim, Nuhad K
Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumour proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumour cells, which led to the development of various vaccines against the HER2 antigen. This manuscript discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings. This article is protected by copyright. All rights reserved. © 2018 UICC.
Veterinary Pathology, Faculty of Veterinary Medicine, University of Ilorin, Ilorin ... One of these mutations led to an amino acid exchange at position 544 ... organs such as comb, wattle, brain, heart, .... congestion in various tissues and edema of.
... free client handout to share with them. Compounding Veterinary Compounding FDA has withdrawn its draft guidance for ... new guidance, the AVMA is working to ensure veterinary access and animal health are protected. NEWS & ALERTS ...
2Department of Veterinary Medicine, University of Nigeria, Nsukka. 3Veterinary. Teaching ... salivation, cornea opacity, haematuria and convulsion were observed in 20, 8, 2, 4, 1 and 3 of the patients ... intravenous fluid administration either for.
Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel
Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.
Krzeminski, M.; Lass, P.; Teodorczyk, J.; Krajka, J.
The veterinary use of radionuclide techniques dates back to the mid-sixties, but its more extensive use dates back to the past two decades. Veterinary nuclear medicine is focused mainly on four major issues: bone scintigraphy - with the majority of applications in horses, veterinary endocrinology - dealing mainly with the problems of hyperthyreosis in cats and hyperthyreosis in dogs, portosystemic shunts in small animals and veterinary oncology, however, most radionuclide techniques applied to humans can be applied to most animals. (author)
He, Yongqun; Racz, Rebecca; Sayers, Samantha; Lin, Yu; Todd, Thomas; Hur, Junguk; Li, Xinna; Patel, Mukti; Zhao, Boyang; Chung, Monica; Ostrow, Joseph; Sylora, Andrew; Dungarani, Priya; Ulysse, Guerlain; Kochhar, Kanika; Vidri, Boris; Strait, Kelsey; Jourdian, George W; Xiang, Zuoshuang
The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.
Hetron Mweemba Munang’andu
Full Text Available Aquaculture is one of the most rapidly expanding farming systems in the world. Its rapid expansion has brought with it several pathogens infecting different fish species. As a result, there has been a corresponding expansion in vaccine development to cope with the increasing number of infectious diseases in aquaculture. The success of vaccine development for bacterial diseases in aquaculture is largely attributed to empirical vaccine designs based on inactivation of whole cell (WCI bacteria vaccines. However, an upcoming challenge in vaccine design is the increase of intracellular bacterial pathogens that are not responsive to WCI vaccines. Intracellular bacterial vaccines evoke cellular mediated immune (CMI responses that “kill” and eliminate infected cells, unlike WCI vaccines that induce humoral immune responses whose protective mechanism is neutralization of extracellular replicating pathogens by antibodies. In this synopsis, I provide an overview of the intracellular bacterial pathogens infecting different fish species in aquaculture, outlining their mechanisms of invasion, replication, and survival intracellularly based on existing data. I also bring into perspective the current state of CMI understanding in fish together with its potential application in vaccine development. Further, I highlight the immunological pitfalls that have derailed our ability to produce protective vaccines against intracellular pathogens for finfish. Overall, the synopsis put forth herein advocates for a shift in vaccine design to include CMI-based vaccines against intracellular pathogens currently adversely affecting the aquaculture industry.
of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...
...] Data Standards for Electronic Interstate Certificates of Veterinary Inspection AGENCY: Animal and Plant... data standards required to generate an official interstate certificate of veterinary inspection (ICVI... interstate certificate of veterinary inspection (ICVI). The standards were developed with the National...
...] Draft Guidelines on Pharmacovigilance of Veterinary Medicinal Products: Electronic Standards for... Requirements for the Registration of Veterinary Medicinal Products (VICH) has developed a draft guideline titled ``Pharmacovigilance of Veterinary Medicinal Products: Electronic Standards for Transfer of Data...
Parida, S.; Walsh, E.P.; Anderson, J.; Baron, M.D.; Barrett, T.
Rinderpest is an economically devastating disease of cattle (cattle plague), but a live-attenuated vaccine has been very successfully used in a global rinderpest eradication campaign. As a consequence, the endemic focus of the virus has been reduced to an area in eastern Africa known as the Kenya-Somali ecosystem. Although the vaccine is highly effective, it has a drawback in that vaccinated animals are serologically indistinguishable from those that have recovered from natural infection. In the final stages of the eradication campaign, when vaccination to control the spread of disease will only be used in emergencies to contain an outbreak, a marker vaccine would be a very useful tool to monitor possible wild virus spread outside the vaccination area. Marker vaccines for rinderpest, and other viruses with negative-sense RNA genomes, can now be produced using reverse genetics, and the development of such marker vaccines for rinderpest virus is described. (author)
Full Text Available ABSTRACT The study was conducted based on the information collected on rural properties in the state of Goiás, during practical classes of Surgical Clinic in Large Animals at the Veterinary Hospital of the Escola de Veterinária e Zootecnia of the Universidade Federal de Goiás and during the implementation of outreach projects developed by the institution. An acropostite-phimosis surgical procedure in the bulls in the field was selected, lasting over 30 minutes and requiring movements, posture and strength on the part of the surgeon. Devices were proposed and developed to provide improved comfort and safety to surgeons. The first device was a stool to be used by the professional during the execution of the surgical intervention. The use enabled the surgeon to sit down and rest their feet on the ground, reducing knee bending and distributing the support forces in various muscle groups. For the movement restriction of the surgeon, another accessory was developed to support the foreskin of the animal. Made of wood, this other device serves as a support for keeping the foreskin away from the ground and close to the surgeon. Its length, width and thickness established a good relation with the stool height, providing minimal discomfort to the professional. The third device was designed to assist in the immobilization of the animal and increase safety for the patient and surgical team. A fourth accessory was designed to protect the scapular region and avoid the occurrence of injuries in the radial nerve, myopathies and traumas during the rollover or prolonged stay of the animal in lateral decubitus. The choice of the shape, dimensions and softness of the device was mainly based on the weight of the animal. Such devices have proven to be effective, reducing the time of surgery, making cervical and lumbar movement easier, in addition to providing better support to the surgeon, reducing risks of musculoskeletal diseases.
Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R
When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights
Lidewij C. M. Wiersma
Full Text Available Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.
Sell, Bartosz; Sniegocki, Tomasz; Zmudzki, Jan; Posyniak, Andrzej
Reported here is a new analytical multiclass method based on QuEChERS technique, which has proven to be effective in diagnosing fatal poisoning cases in animals. This method has been developed for the determination of analytes in liver samples comprising rodenticides, carbamate and organophosphorus pesticides, coccidiostats and mycotoxins. The procedure entails addition of acetonitrile and sodium acetate to 2 g of homogenized liver sample. The mixture was shaken intensively and centrifuged for phase separation, which was followed by an organic phase transfer into a tube containing sorbents (PSA and C18) and magnesium sulfate, then it was centrifuged, the supernatant was filtered and analyzed by liquid chromatography tandem mass spectrometry. A validation of the procedure was performed. Repeatability variation coefficients forensic toxicology cases.
Jan 12, 2018 ... Engineering a wild fast-growing Mycoplasma bacterium to generate a novel vaccine for contagious caprine ... Engineering vaccines against hemorrhagic septicemia in ruminants ... Solutions. Careers · Contact Us · Site map.
Jan 12, 2018 ... Engineering a wild fast-growing Mycoplasma bacterium to generate a novel vaccine for contagious caprine ... Engineering vaccines against hemorrhagic septicemia in ruminants ... Solutions. Careers · Contact Us · Site map.
A H Bandivdekar
Full Text Available Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4, protein hyaluronidase (PH-20, and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80kDa HSA is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80kDa HSA (Peptide NT and its peptides (Peptides 1, 2, 3 and 4 obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80kDA HAS suggest that the synthetic Peptide-1 of 80kDa HSA is the promising candidate for development of male contraceptive vaccine.
Full Text Available Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO, the European Medicines Agency (EMA, and the United States Food and Drug Administration (USFDA. The manuscript describes the objectives, study populations, study designs, study site, and outcome(s of each phase (Phase I-III of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.
Harrus, S; Waner, T; Aizenberg; Safra, N; Mosenco, A; Radoshitsky, M; Bark, H
Two different vaccination protocols were compared with regard to the development of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV) and then two weeks later with a trivalent vaccine containing modified live canine distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL). The CPV and DHL vaccine protocols were administered a further two times, at two-week intervals. Group 2 was vaccinated with three consecutive multivalent vaccines containing modified live canine distemper virus, canine parvovirus, parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four-week intervals. All puppies were first vaccinated at the age of eight weeks. Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD during the study period. Dogs in group 2 had more episodes of HOD than those in group 1. Dogs in group 1 developed higher antibody titres to canine distemper virus and parvovirus compared with those in group 2. Only two out of the 10 dogs developed protective antibody titres to parvovirus. The results of this study suggest that the two different vaccination protocols affected the pattern of appearance of HOD and immunisation in this litter of Weimaraner puppies. The results obtained and the previously reported data suggest that a larger controlled study is needed to further elucidate the effect of different vaccination protocols on HOD and immunisation in Weimaraner puppies.
Amorij, J-P; Huckriede, A; Wilschut, J; Frijlink, H W; Hinrichs, W L J
Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought
Oirschot, van J.T.; Kaashoek, M.J.; Rijsewijk, F.A.M.
This review deals with conventional and modern bovine herpesvirus 1 (BHV1) vaccines. Conventional vaccines are widely used to prevent clinical signs of infectious bovine rhinotracheitis. The use of conventional vaccines, however, does not appear to have resulted in reduction of the prevalence of
E M D L van der Heijden
Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study
... of knowledge about HCMV biology and epidemiology and on vaccine development strategies. Topics for discussion will include: (1) HCMV epidemiology and diagnosis, (2) HCMV immunology and virology, (3...
Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.
Pagliusi, Sonia; Ting, Ching-Chia; Khomvilai, Sumana
The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy
Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822
Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon
Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery.
Kanojia, Gaurav; Have, Rimko ten; Soema, Peter C.; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon
ABSTRACT Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery. PMID:28925794
RAJU.S , UMA MAHESHWARA RAO.V
The concept of vaccination has been around forcenturies .Vaccines constitutes cost-effective measures forpreventing disease. Advances in biotechnology and anunderstanding of the inductive and effector components ofimmune responses have ushered in a „golden age‟ ofvaccine development and implementation. Many licensedvaccines have one or more ideal characteristics, but nonemanifests them all. Of the generic vaccine technologies andvaccination strategies in different stages of development,some h...
Cervical cancer and other diseases related to human papillomavirus (HPV) represent a global public health problem. Safe and effective vaccines are now available and already used in many industrialized countries. Immunization offers the best hope for protecting the population against a disease that is the second most deadly cancer in the developing world and the first most deadly in Africa. The World Health Organization currently recommends introduction of HVP vaccination in developing countries. Widespread vaccination could be beneficial in numerous domains other than primary prevention of cervical cancer. Efforts to overcome the numerous obstacles and speed up implementation of HVP vaccination programs are now underway in many areas ranging from related scientific issues such as epidemiology and clinical research to administrative concerns such as healthcare economics, vaccination guidelines, public acceptation, program funding, and universal access. Vaccine manufacturers have committed themselves to working in partnership with national and international organizations to ensure access to HPV vaccine for all countries regardless of economic level, Although numerous issues must be resolved to optimize the use of HPV vaccines and ensure synergistic integration of vaccination, screening and treatment, current initiatives and efforts should allow introduction of HPV vaccination in developing countries in a not too distant future.
The acquisition of substantial anti-malarial protection in people naturally exposed to P. falciparum is often cited as evidence that malaria vaccines can be developed, but is rarely used to guide the development. We are pursuing the development of vaccines based on antigens and immune responses...
Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara
Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.
Federal Laboratory Consortium — Mission:To provide quality veterinary medical care and environmental enrichment programs for all animals, representing nine different species.To provide guidance for...
Giuseppina Li Pira
Full Text Available Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th and by cytolytic T lymphocytes (CTL is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost.
Plosker, Greg L
The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine
McDonough, S P; McEwen, B J
Veterinary forensic pathology is emerging as a distinct discipline, and this special issue is a major step forward in establishing the scientific basis of the discipline. A forensic necropsy uses the same skill set needed for investigations of natural disease, but the analytical framework and purpose of forensic pathology differ significantly. The requirement of legal credibility and all that it entails distinguishes the forensic from routine diagnostic cases. Despite the extraordinary depth and breadth of knowledge afforded by their training, almost 75% of veterinary pathologists report that their training has not adequately prepared them to handle forensic cases. Many veterinary pathologists, however, are interested and willing to develop expertise in the discipline. Lessons learned from tragic examples of wrongful convictions in medical forensic pathology indicate that a solid foundation for the evolving discipline of veterinary forensic pathology requires a commitment to education, training, and certification. The overarching theme of this issue is that the forensic necropsy is just one aspect in the investigation of a case of suspected animal abuse or neglect. As veterinary pathologists, we must be aware of the roles filled by other veterinary forensic experts involved in these cases and how our findings are an integral part of an investigation. We hope that the outcome of this special issue of the journal is that veterinary pathologists begin to familiarize themselves with not only forensic pathology but also all aspects of veterinary forensic science. © The Author(s) 2016.
Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi
Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.
Petrie, Joshua G; Gordon, Aubree
The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies such as prospective, longitudinal cohort studies are essential to the completion of these objectives. In this review, we discuss the contributions of epidemiological studies to our current knowledge of vaccines and correlates of immunity, and how they can contribute to the development and evaluation of the next generation of influenza vaccines. These studies have been critical in monitoring the effectiveness of current influenza vaccines, identifying issues such as low vaccine effectiveness, reduced effectiveness among those who receive repeated vaccination, and issues related to egg adaptation during the manufacturing process. Epidemiological studies have also identified population-level correlates of protection that can inform the design and development of next generation influenza vaccines. Going forward, there is an enduring need for epidemiological studies to continue advancing knowledge of correlates of protection and the development of immunity, to evaluate and monitor the effectiveness of next generation influenza vaccines, and to inform recommendations for their use.
Moulin, A M
The aim of this paper is to introduce the one hundred years of vaccination that has passed since Louis Pasteur first coined this generic term. According to the late Jonas Salk, vaccinology is a science encompassing all aspects of vaccine from its conception in the laboratory to its production by companies and its application and distribution in the field. In this historical survey I explore how vaccination never consisted of a simple and uniform application of a rational model, but rather diverged along various pathways, several of which were discarded in retrospect as being hazardous, and I analyse the ongoing interplay between rational and inventive thinking.
Scholarship on the Tanzanian Rinderpest epizootic of the 1890s has assumed that German colonizers understood from the start that they were confronting the same disease that had afflicted Eurasia for centuries. Outward indicators of the epizootic, known locally as sadoka, especially wildlife destruction, were unknown in Europe, leading German veterinarians to doubt that the African disease was Rinderpest. Financial constraints and conflicting development agendas, especially tension between ranching and pastoralism, deterred early colonial applications of veterinary science that might have led to an early diagnosis. European veterinarians, guarding their authority against medical researchers, opposed inoculation therapies in the case of Rinderpest in favor of veterinary policing despite recent breakthroughs in vaccine research. The virus was not identified before reaching South Africa in 1896, but this breakthrough had little influence on policy in East Africa. Yet emergent international disease conventions directed at bubonic plague entangled with veterinary policy in East Africa.
paratuberculosis provide only partial protection and interfere with diagnostic tests for JD and surveillance for bovine TB. In contrast, recombinant subunit vaccines can be designed to be used without compromising control of bTB and Map. Taking advantage of data from mouse TB studies, and early Map vaccination...... in macrophages. The disease progression is very slow with neonatal animals being the most susceptible to infection, but without development of detectable IFN-γ responses for months after infection and rarely with clinical disease before the second or third year of life. Available whole cell vaccines against......- and field-studies we developed a vaccine with a single recombinant fusion protein comprising four acute-stage antigens (Ags) and one latent-stage Ag formulated in adjuvant (FET-vaccine). In post-exposure vaccination of calves and goats with necropsy 8-12 months post inoculation, we determined...
Mahoney, Richard T; Krattiger, Anatole; Clemens, John D; Curtiss, Roy
This paper offers a framework for managing a comprehensive Global Access Strategy for new vaccines in developing countries. It is aimed at strengthening the ability of public-sector entities to reach their goals. The Bill and Melinda Gates Foundation and The Rockefeller Foundation have been leaders in stimulating the creation of new organizations - public/private product development partnerships (PDPs) - that seek to accelerate vaccine development and distribution to meet the health needs of the world's poor. Case studies of two of these PDPs - the Salmonella Anti-pneumococcal Vaccine Program and the Pediatric Dengue Vaccine Initiative - examine development of such strategies. Relying on the application of innovation theory, the strategy leads to the identification of six Components of Innovation which cover all aspects of the vaccine innovation process. Appropriately modified, the proposed framework can be applied to the development and introduction of other products in developing countries including drugs, and nutritional and agricultural products.
Gershon, Anne A.
Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.
Gershon, Anne A., E-mail: firstname.lastname@example.org [Department of Pediatrics, Columbia University College of Physicians and Surgeons, 620W. 168th Street, NY, NY 10032 (United States)
Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.
Aghebati-Maleki, Leili; Bakhshinejad, Babak; Baradaran, Behzad; Motallebnezhad, Morteza; Aghebati-Maleki, Ali; Nickho, Hamid; Yousefi, Mehdi; Majidi, Jafar
Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mamm...
Efficacy will be examined in mice by vaccination at 7, 14, and 21 days after tumor induction through monitoring tumor incidence, size, survival...intradermal B16 solid tumor model. Mice were inoculated with B16F10 and 3 days later were vaccinated with MCMVgp100KGP. For one experiment, mice were...We are now comparing the efficacy of this new vaccine to other single epitope virus vectors. Q6. can you please also clarify the AIMS of the SPARK
Quinn, P. J
"Veterinary Microbiology is one of the core subjects for veterinary students. Fully revised and expanded, this new edition covers every aspect of veterinary microbiology for students in both paraclinical and clinical years...
The Sahel Journal of Veterinary Sciences is the official journal of the Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria. The journal welcomes original research articles, short communications and reviews on all aspects of veterinary sciences and related disciplines.
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Open Veterinary Journal is a peer reviewed international open access online and printed journal that publishes high-quality original research articles, reviews, short communications and case reports dedicated to all aspects of veterinary sciences and its related subjects. Other websites associated with this journal: ...
'Central Diagnostic, National Veterinary Research Institute Vom, Plateau State, Nigeria, 'Department of Veterinary Medicine. Ahmadu Bello ..... environment as reported by (Olabode et al., 2009; Okwor and Eze, 2011;Jwander et al., 2013b). Farmers who had the same complaints of. Marek's disease from the same source of.
Anand, Sudhir; Bärnighausen, Till
Vaccine-preventable diseases cause more than 1 million deaths among children in developing countries every year. Although health workers are needed to do vaccinations, the role of human resources for health as a determinant of vaccination coverage at the population level has not been investigated. Our aim was to test whether health worker density was positively associated with childhood vaccination coverage in developing countries. We did cross-country multiple regression analyses with coverage of three vaccinations--measles-containing vaccine (MCV); diphtheria, tetanus, and pertussis (DTP3); and poliomyelitis (polio3)--as dependent variables. Aggregate health worker density was an independent variable in one set of regressions; doctor and nurse densities were used separately in another set. We controlled for national income per person, female adult literacy, and land area. Health worker density was significantly associated with coverage of all three vaccinations (MCV p=0.0024; DTP3 p=0.0004; polio3 p=0.0008). However, when the effects of doctors and nurses were assessed separately, we found that nurse density was significantly associated with coverage of all three vaccinations (MCV p=0.0097; DTP3 p=0.0083; polio3 p=0.0089), but doctor density was not (MCV p=0.7953; DTP3 p=0.7971; polio3 p=0.7885). Female adult literacy was positively associated, and land area negatively associated, with vaccination coverage. National income per person had no effect on coverage. A higher density of health workers (nurses) increases the availability of vaccination services over time and space, making it more likely that children will be vaccinated. After controlling for other determinants, the level of income does not contribute to improved immunisation coverage. Health workers can be a major constraining factor on vaccination coverage in developing countries.
Swan, G E; Kriek, N P J
Veterinary education commenced in South Africa in 1920 at the Onderstepoort Veterinary Institute in South Africa in association with the Transvaal University College, now the University of Pretoria. Sir Arnold Theiler, Director of Veterinary Research and Education, was the first Dean. Today there are 46 veterinary training institutions in Africa of which 21 are in sub-Saharan Africa. Veterinary services are indispensable to the sustained health and wellbeing of animals and humans, and agricultural economies of countries worldwide. Veterinary education, postgraduate training, and research, and adequate numbers of veterinarians, are essential to satisfy the millennium development goals, the objectives of NEPAD and the African Union, and the agreements regulating international trade. The relevance of the veterinary profession internationally is currently subject to profound scrutiny. Its contributions are assessed against major environmental, demographic, political, disease, technological and economic needs. The scope of veterinary training in future will have to emphasise veterinary public health, food safety, emerging diseases, international trade, bioterrorism, and biomedical research, within the context of a one-health system focusing on the interface between wildlife, domesticated animals, humans, and their environment. Within the context of time available, it would mean reducing the time allocated to training in the field of companion animals. A brief history and scope of veterinary education; current international trends in veterinary education and provisioning; and some perspectives on future veterinary training and initiatives applicable to Africa are provided.
Kunisawa, Jun; Kurashima, Yosuke; Kiyono, Hiroshi
Oral vaccine has been considered to be a prospective vaccine against many pathogens especially invading across gastrointestinal tracts. One key element of oral vaccine is targeting efficient delivery of antigen to gut-associated lymphoid tissue (GALT), the inductive site in the intestine where antigen-specific immune responses are initiated. Various chemical and biological antigen delivery systems have been developed and some are in clinical trials. In this review, we describe the immunological features of GALT and the current status of antigen delivery system candidates for successful oral vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.
Costa Barbosa Bessa, Theolis; Santos de Aragão, Erika; Medeiros Guimarães, Jane Mary; de Araújo Almeida, Bethânia
Based on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement.
Full Text Available Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230 that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.
This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. This endemic livestock disease affects the livelihoods of more than 24 million cattle producers and results in annual losses estimated at US$1 billion across sub-Saharan Africa. About the vaccine Using ...
Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon
Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this
Live attenuated brucellosis vaccines have been available for protecting domestic livestock against B. melitensis or B. abortus for more than 60 years. Current vaccines are effective in preventing abortion and transmission of brucellosis, but poor at preventing infection or seroconversion. In addit...
Linear tomography has been well known since the thirties of the last century. Before and alter World War II attempts of taking cross sections were done radiographically, but image quality was extremely poor. About 1960 A.M. Cormack developed a possibility to measure body densities for radiation therapy. After having attempted digitization of x-ray intensities during tissue penetration, G.N. Hounsfield constructed the first scanner in 1972 - in the first run only to examine the head. Improvements of technology lead to a series of generations of scanners which ended in the development of spiral CT and multi-slice detectors. In veterinary medicine the first papers on the use of CT in small animals were published by clinicians in the United States and in Germany nearly at the same time in 1980. A number of reports appeared afterwards from clinicians worldwide. The technique for examination of the horse was first described in the United States in 1986; in Europe the first CT scanner examining horses was established in Utrecht. At the Radiology Clinic of the University of Veterinary Medicine, Vienna, the first scanner for clinical use started to operate in summer 1993. The diagnostic possibilities improved in 1997 by introduction of a large animal weight bearing table. A new spiral CT has been put into operation in February 2001. CT has dramatically improved diagnostic accuracy in diagnostic imaging and lead to advanced therapy and prognosis for the patient in many specialist fields of veterinary medicine, e.g. neurosurgery, neurology, oncology, or orthopedics. (author)
Dixon, D M; Casadevall, A; Klein, B; Mendoza, L; Travassos, L; Deepe, G S
Vaccine approaches to infectious diseases are widely applied and appreciated. Disciplines such as bacteriology and virology have a rich history of successful vaccine development. The complexity of eukaryotic systems presents additional challenges to the development of vaccines against them. These challenges are being met in the fields of parasitology, and are being revisited for application in oncology. Vaccine opportunities exist in medical mycology. The National Institute of Allergy and Infectious Diseases has held a series of workshops in medical mycology where the need to develop vaccines for fungal diseases was noted and where important opportunities were discussed. Major advances in vaccinology and the technology of antigen preparation and delivery have increased feasibility and heightened interest. The recent epidemic of coccidioidomycosis in the American Southwest has demonstrated the need for developing a vaccine as an effective preventive measure for those living in and for those who subsequently move into regions with the endemic mycoses. The XIIth Congress of the International Society for Human and Animal Mycology included a symposium that summarized new vaccination strategies for selected fungi: Candida albicans, Coccidioides immitis, and Trichophyton verrucosum. The goal of the present summary is to provide representative examples of continuing efforts relating to vaccine development within the medical mycological community highlighting Blastomyces dermatidis, Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Pythiumn insidiosum.
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...
Zuhair Bani Ismail
Full Text Available The objective of this review article was to summarize the most recent clinical field trials that have been published evaluating the use of different types of vaccines against mastitis pathogens in dairy cows. Mastitis is one of the most common and economically important diseases in dairy cows in the world. The disease is considered an important welfare issue facing the dairy industry in addition to the loss of production and premature removal or death of affected cows. Losses are also related to high cost of veterinary medicines and the cost of unsalable milk of treated cows. Mastitis can be caused by either contagious or environmental pathogens both of which are best prevented rather than treated. In addition to the application of best management practices in the parlor during milking, vaccination against common udder pathogens is widely practiced in many dairy farms to prevent or reduce the severity of clinical mastitis. In this review, the most recent clinical field studies that evaluated the use of different types of vaccines in dairy cows are summarized.
Schiffer, Joshua T; Gottlieb, Sami L
Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs, AFPL (proteoliposome and AFCo (cochleate, were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.
Full Text Available Kwaku Poku Asante, George Adjei, Yeetey Enuameh, Seth Owusu-Agyei Kintampo Health Research Centre, Kintampo, Brong Ahafo Region, Ghana Abstract: Though the burden of malaria has decreased in the last decade in some sub-Saharan African countries, it is still high in others, and there is no malaria vaccine in use. The development of malaria vaccines in combination with current control programs could be effective in reducing the malaria burden. In this paper, we review and discuss the progress made in the RTS,S malaria vaccine development and considerations for its postapproval process. We conclude that the development of malaria vaccines has been a long process confronted with challenges of funding, difficulty in identifying malaria antigens that correlate with protection, and development of adjuvant systems among others. The scientific approval of the vaccine by the European Medicines Agency in July 2015 and subsequent recommendations for pilot implementation studies by the World Health Organization made history as the first human parasite vaccine. It is also a major public health achievement as the vaccine has the potential to prevent thousands of malaria cases. However, there are implementation challenges such as cold chain systems, community acceptance, and monitoring of adverse events post-licensure that need to be carefully addressed. Keywords: malaria, vaccines, challenges, introduction, Africa, implementation considerations
Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M
Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.
Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon
Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....
Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M
Multi-residue methods for veterinary drugs or pesticides in food are increasingly often based on ultra performance liquid chromatography (UPLC) coupled to high resolution mass spectrometry (HRMS). Previous available time of flight (TOF) technologies, showing resolutions up to 15,000 full width at half maximum (FWHM), were not sufficiently selective for monitoring low residue concentrations in difficult matrices (e.g. hormones in tissue or antibiotics in honey). The approach proposed in this paper is based on a single stage Orbitrap mass spectrometer operated at 50,000 FWHM. Extracts (liver and kidney) which were produced according to a validated multi-residue method (time of flight detection based) could not be analyzed by Orbitrap because of extensive signal suppression. This required the improvement of established extraction and clean-up procedures. The introduced, more extensive deproteinzation steps and dedicated instrumental settings successfully eliminated these detrimental suppression effects. The reported method, covering more than 100 different veterinary dugs, was validated according to the EU Commission Decision 2002/657/EEC. Validated matrices include muscle, kidney, liver, fish and honey. Significantly better performance parameters (e.g. linearity, reproducibility and detection limits) were obtained when comparing the new method with the older, TOF based method. These improvements are attributed to the higher resolution (50,000 versus 12,000 FWHM) and the superior mass stability of the of the Orbitrap over the previously utilized TOF instrument. Copyright © 2010 Elsevier B.V. All rights reserved.
This bibliography of in-print veterinary medical books published in English may be used as an acquisitions or evaluation tool for developing the monograph component of new veterinary medicine collections or existing science, technology, and medicine collections where veterinary medicine is in the scope of the collection. The bibliography is divided into 34 categories and consists of bibliographic information for 419 titles. The appendix contains an author/editor index. Prices for all entries are in US dollars, except where another currency is noted. The total cost of all books in the bibliography is $43,602.13 (US).
Horcajo, P; Regidor-Cerrillo, J; Aguado-Martínez, A; Hemphill, A; Ortega-Mora, L M
Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major economic losses associated with the disease. Currently, there is no treatment or vaccine available against abortion or transmission caused by Neospora caninum infection in cattle. However, vaccination is considered the best measure of control against bovine neosporosis. Several host and parasite factors can influence the dynamics of the infection in bovines. Moreover, the availability of well-defined infection models is a key factor for the evaluation of vaccine candidates. However, working with cattle is not easy due to difficult handling, facilities and costs, and therefore, 'more affordable' models could be used for screening of promising vaccines to establish proof of concept. So far, live-attenuated vaccines have shown good efficacy against exogenous transplacental transmission; however, they have relevant disadvantages and associated risks, which render inactivated or subunit vaccines the best way forward. The identification of novel potential targets and vaccines, and the application of innovative vaccine technologies in harmonized experimental animal models, will accelerate the development of an effective vaccine against bovine neosporosis. © 2016 John Wiley & Sons Ltd.
Hazel, Susan J; Heberle, Nicole; McEwen, Margaret-Mary; Adams, Karen
Team-based learning (TBL) was implemented into a first-year course (Principles in Animal Behaviour, Welfare and Ethics) for BSc Veterinary Bioscience (VB) and Animal Science (AS) students. TBL is now used widely in teaching medical students, but has had more limited uptake in veterinary education. This study reports its use over 2 years with cohorts of 126 and 138 students in 2011 and 2012, respectively. Average individual marks for multiple-choice question (MCQ) tests in the Readiness Assurance component of TBL were higher for the teams than for individuals for each session, explicitly demonstrating the advantages of teamwork. Students reported that they felt actively involved and that TBL helped them both with their learning and in developing other important skills, such as teamwork and communication. Qualitative analysis of written feedback from the students revealed positive themes of discussion, application, revelation, socializing, engagement, clarification, and retention/revision. In 2011 negative comments included the need to shorten the TBL sessions, but in 2012 tightening of the timelines meant that this was no longer a major concern. Requests to provide better introductory and background materials and ambiguity in questions in the TBL activities were what students least liked about the TBL. However, most comments were positive rather than negative in nature, and many students preferred the TBL to lectures. With requirements for curricula to teach professional skills, such as communication and teamwork, and the positive results from TBL's implementation, it is hoped that this study will encourage others to trial the use of TBL in veterinary education.
Pavli, Androula; Katerelos, Panagiotis; Smeti, Paraskevi; Maltezou, Helena C
Meningococcal meningitis is a serious disease. Travel-associated infection for the general traveller is low; however regular epidemics in indigenous population, particularly in sub-Saharan Africa are responsible for significant morbidity and mortality. Our aim was to assess meningococcal vaccination for international travellers from Greece. A prospective questionnaire-based study was conducted during 2009-2013. A total of 5283 travellers were studied (median age: 39.2 years); Meningococcal tetravalent vaccine (A,C,W135,Y) was delivered to 1150 (21.8%) of them. Of those who travelled to the Middle East and sub-Saharan Africa, 73.1% and 21.2% received meningococcal vaccine, respectively. Of those travellers who travelled to sub-Saharan Africa from November to June and from July to October, 22.1% and 20.6% were vaccinated with meningococcal vaccine, respectively. Of all travellers who travelled for travelled for recreation, and 13.8% of those who travelled for work. Of travellers who stayed in urban, in rural, and in urban and rural areas, 32%, 11.6% and 12.7% were vaccinated, respectively. Meningococcal vaccine was delivered to 29.2%, 21.1%, 19.4% and 5.1% of those who stayed in hotels, at local people's home, in camps, and on ships, respectively. The association of meningococcal vaccine administration with the destination, duration and purpose of travel, area of stay and type of accommodation was statistically significant. There is a need to improve meningococcal vaccine recommendations for travellers from Greece, particularly for high risk populations, such as VFRs, business travellers and those visiting sub-Saharan Africa especially during the dry season. Copyright © 2016 Elsevier Ltd. All rights reserved.
Vannice, Kirsten S; Wilder-Smith, Annelies; Barrett, Alan D T; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P; Endy, Tim; Harris, Eva; Innis, Bruce L; Katzelnick, Leah C; Smith, Peter G; Sun, Wellington; Thomas, Stephen J; Hombach, Joachim
Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available African swine fever (ASF is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated.
Vallat, B; Mallet, E
As an effect of increased globalisation, animal diseases, in particular those transmissible to man, have an immediate global economic and social impact. This fact, dramatically illustrated by the current avian influenza epizootic in South-East Asia and Eastern Europe, clearly demonstrates the crucial importance of the national Veterinary Services (VS) for the prevention, early detection and response for the efficient control of animal diseases. Complying with this mission for the VS presupposes the existence of appropriate governance and legislation and of an official system to control their quality and reliability- an obvious weakness in many developing and in transition countries. The World Organisation for Animal Health (OIE) has therefore developed a project aiming at strengthening the VS in those countries facing the greatest animal health threats and to bring them into line with OIE international standards already adopted by the same countries. Based on the evaluation of the VS and subsequent actions at the global, regional and national levels, the project will have a significant beneficial impact on the targeted countries as well as the international community as a whole, not only in the fields of agriculture, food security and production, and food safety, but also for the local and global prevention of emerging and re-emerging diseases of veterinary and public health importance. The project will be implemented in strong collaboration with the Food and Agriculture Organization. The actions proposed must be considered eligible for the concept of International Public Good.
Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection.
Several barriers limit the development of vaccines against sexually transmitted diseases (STIs). Critical scientific information is missing that makes the feasibility and the likelihood of success of vaccines against genital herpes, chlamydia, gonorrhea and trichomonas uncertain: the immunity induced by natural infection is absent or imperfect which seriously limits the capacity to define the types of immune responses that an effective vaccine must induce. Reliable animal models are lacking and a number of crucial clinical questions are still unanswered about the goal of these vaccines and definition of endpoints for clinical trials. In the absence of a clear recognition of the need for vaccines against these diseases, there is no motivation for public or private research and industry to invest in the development of vaccines against STIs. The STI burden should be evaluated not only in terms of mortality and morbidity, but also in terms of economic and psycho-social impact. A global public-private consortium could mobilize the joint efforts of all stakeholders involved in the research, development and implementation of STI vaccines of the public and private sectors; ensure that sufficient resources are applied to R&D of vaccines against these STIs; and provide the pull-push forces that are necessary to overcome the barriers to develop safe and effective vaccines against these diseases. Copyright © 2014. Published by Elsevier Ltd.
Ciarlet, Max; Schödel, Florian
Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.
Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried
Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.
Chitradevi, S T S; Kaur, G; Sivaramakrishna, U; Singh, D; Bansal, A
Shigellosis is an acute bacillary diarrheal disease caused by the gram negative bacillus Shigella. The existence of multiple Shigella serotypes and their growing resistance to antibiotics stress the urgent need for the development of vaccine that is protective across all serotypes. Shigella's IpaB antigen is involved in translocon pore formation, promotes bacterial invasion and induces apoptosis in macrophages. S. Typhi GroEL (Hsp 60) is the immunodominant antigen inducing both arms of immunity and has been explored as adjuvant in this study. The present study evaluates the immunogenicity and protective efficacy of recombinant IpaB domain-GroEL fusion protein in mice against lethal Shigella infection. The IpaB domain and GroEL genes were fused using overlap extension PCR and cloned in pRSETA expression vector. Fused gene was expressed in Escherichia coli BL-21 cells and the resulting 90 KDa fusion protein was purified by affinity chromatography. Intranasal (i.n.) immunization of mice with fusion protein increased the IgG and IgA antibody titers as compared to the group immunized with IpaB and GroEL and control PBS immunized group. Also IgG1 and IgG2a antibodies induced in fusion protein immunized mice were higher than co-immunized group. Significant increase in lymphocyte proliferation and cytokine levels (IFN-γ, IL-4 and IL-10), indicates induction of both Th1 and Th2 immune responses in both immunized groups. Immunization with fusion protein protected 90-95% of mice whereas 80-85% survivability was observed in co-immunized group against lethal challenge with S. flexneri, S. boydii and S. sonnei. Passive immunization conferred 60-70% protection in mice against all these Shigella species. Organ burden and histopathology studies also revealed significant decrease in lung infection as compared to the co-immunized group. Since IpaB is the conserved dominant molecule in all Shigella species, this study will lead to an ideal platform for the development of safe
McAllister, Shane C; Schleiss, Mark R
Herpes simplex viruses 1 and 2 are human pathogens that lead to significant morbidity and mortality in certain clinical settings. The development of effective antiviral medications, however, has had little discernible impact on the epidemiology of these pathogens, largely because the majority of infections are clinically silent. Decades of work have gone into various candidate HSV vaccines, but to date none has demonstrated sufficient efficacy to warrant licensure. This review examines developments in HSV immunology and vaccine development published since 2010, and assesses the prospects for improved immunization strategies that may result in an effective, licensed vaccine in the near future.
Nyamathi, AM; Fahey, JL; Sands, H; Casillas, AM
Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapongrade material, the potential exists f...
Corresponding author: Email: email@example.com; Tel No:+2348037811882 ... and veterinary medicine as potent anti-inflammatory, immunosuppressive and .... steroid skeleton, similar to hydrocortisone. ... for pregnant women at risk of preterm birth.
... Journal are the Research Workers, Veterinary Clinicians, Animal Scientists, Field Officers ... Prevalence and risk factors for Ascaris and Cryptosporidium infestations in ... Mastitis pathogens prevalent in dairy cattle at Magadu farm, Morogoro- ...
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Control Services, Federal Ministry of Agriculture, Abuja; 9National Veterinary Research Institute, P.M.B 01 Vom,. Nigeria. *Corresponding ... because the poultry industry contributes ..... holidays have been identified as source of transmission ...
Ethiopian Veterinary Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2011) >. Log in or Register to get access to full text downloads.
Kakkar, Manish; Abbas, Syed Shahid; Kumar, Ashok; Hussain, Mohammad Akhtar; Sharma, Kavya; Bhatt, Purvi Mehta; Zodpey, Sanjay
Veterinary public health (VPH) is ideally suited to promote convergence between human, animal and environmental sectors. Recent zoonotic and emerging infectious disease events have given rise to increasing calls for efforts to build global VPH capacities. However, even with their greater vulnerability to such events, including their economic and livelihood impacts, the response from low-and middle-income countries such as India has been suboptimal, thereby elevating global health risks. Addressing risks effectively at the human-animal interface in these countries will require a clear vision, consistent policies, strategic approach and sustained political commitment to reform and refine the current VPH capacity-building efforts. Only then can the discipline serve its goal of disease prevention, poverty alleviation and support for sustainable livelihoods through improvements in human and animal health.
necropsy at the end of the trial (110 vaccinated; 102 controls. Viable T. solium cysticerci were identified in 20 control pigs (prevalence 19.6%, including 14 animals that had estimated total body burdens of > 1000 cysticerci. No cysticerci were found in any of the vaccinated animals indicating that the vaccine provided a very high level of protection (P< 0.0001 against naturally acquired infection with T. solium in pigs. Combined application of TSOL18 vaccination and a single oxfendazole treatment in pigs is a simple and relatively sustainable procedure that has the potential to control T. solium transmission in endemic areas and, indirectly, reduce the number of new cases of neurocysticercosis in humans. In chapter 6, the similarity of the antibody responses of pigs and mice to TSOL18 antigen is highlighted. Four IgG1 monoclonal antibodies (MoAb were produced against the conformational epitopes of TSOL18. It was shown that pig antisera inhibit the binding of these MoAbs in a competition ELISA, indicating that pig and mouse antibodies against TSOL18 vaccine react with the same conformational epitopes. For this reason, monoclonal antibodies raised in mice immunized with TSOL18 could be a valuable source of antibodies for further characterisation of the host-protective epitopes of the vaccine. A monoclonal antibody-based inhibitive enzyme-linked immunosorbent assay (mi-ELISA was developed. Serum samples of TSOL18-vaccinated and non-vaccinated pigs were used. In all the vaccinated and protected pigs screened at necropsy, anti-TSOL18 antibodies inhibited the binding of a monoclonal antibody (Mab25D12C1 specific to the conformational epitopes of TSOL18 antigen, suggesting an immune response that correlates with protection. This result was in agreement with the results obtained in an indirect ELISA, which showed that all the vaccinated and protected pigs had developed antibodies to the TSOL18 vaccine. In chapter 7 the efficacy of the TSOL18 vaccine is compared with that of
Comerci, D.J.; Ugalde, J.E.; Ugalde, R.A.
Brucella abortus S19 is the most commonly used attenuated live vaccine to prevent bovine brucellosis. In spite of its advantages, S19 has several drawbacks: it is abortive for pregnant cattle, is virulent for humans, and re-vaccination is not advised due to the persistence of anti-lipopolysaccharide (LPS) antibodies that hamper the immunoscreening procedures. For these reasons, there is a continuous search for new bovine vaccine candidates. We have previously characterized the phenotype of the phosphoglucomutase (pgm) gene disruption in Brucella abortus S2308, as well as the possible role for the smooth LPS in virulence and intracellular multiplication. Here we evaluate the vaccine properties of an unmarked deletion mutant of pgm. Western blot analysis of purified lipopolysaccharide and whole-cell extract from Δpgm indicate that it synthesizes O-antigen but is incapable of assembling a complete LPS. In consequence Δpgm has a rough phenotype. Experimental infections of mice indicate that Δpgm is avirulent. Vaccination with Δpgm induces protection levels comparable to those induced by S19, and generates a splenocyte proliferative response and cytokines profile typical of a Th-1 response. The ability of the mutant to generate a strong cellular Th-1 response without eliciting specific O-antigen antibodies highlights the potential use of this mutant as a new live vaccine for cattle. (author)
Full Text Available Ovine enzootic abortion, caused by Chlamydia abortus, leads to important economic losses worldwide. In addition to reproductive failures, infection may impact lamb growth during the first weeks after birth, yet this effect has not been well characterized. Vaccination can help to control the disease but variable efficacy values have been described, possibly related with factors associated with the host, the vaccine, the parameter used for efficacy determination and the challenge conditions. In this context, we evaluated the efficacy of an inactivated standard commercial vaccine and a 1/2 diluted dose in pregnant sheep challenged with C. abortus by examining multiple indicators ofvaccine effect (including incidence of reproductive failures, bacterial excretion, and evolution of weight gain of viable lambs during the first month of life. Three groups of ewes [control non-vaccinated, C (n = 18; vaccinated with standard dose, SV (n = 16 and vaccinated with 1/2 dose, DV (n = 17], were challenged approximately 90 days post-mating and tested using direct PCR (tissue samples and vaginal swabs and ELISA (serum until 31 days post-reproductive outcome. There were not significant differences in the proportions of reproductive failures or bacterial shedding after birth/abortion regardless the vaccination protocol. However, a beneficial effect of vaccination on offspring growth was detected in both vaccinated groups compared with the controls, with a mean increase in weight measured at 30 days of life of 1.5 and 2.5 Kg (p = 0.056 and an increase in the geometric mean of the daily gain of 8.4 and 9.7% in lambs born from DV and SV ewes compared to controls, respectively. Our results demonstrate the effect of an inactivated vaccine in the development of the offspring of C. abortus-infected ewes at a standard and a diluted dose, an interesting finding given the difficulty in achieving sufficient antigen concentration in the production of EAE-commercial vaccines.
Gonçalves, Vagner; Hazarbassanov, Nicolle Queiroz; de Siqueira, Adriana; Florio, Jorge Camilo; Ciscato, Claudia Helena Pastor; Maiorka, Paulo Cesar; Fukushima, André Rinaldi; de Souza Spinosa, Helenice
Agricultural pesticides used with the criminal intent to intoxicate domestic and wild animals are a serious concern in Veterinary Medicine. In order to identify the pesticide carbofuran and its metabolite 3- hydroxycarbofuran in animals suspected of exogenous intoxication a high pressure liquid chromatography with diode array detector (HPLC-DAD) method was developed and validated in stomach contents, liver, vitreous humor and blood. The method was evaluated using biological samples from seven different animal species. The following parameters of analytical validation were evaluated: linearity, precision, accuracy, selectivity, recovery and matrix effect. The method was linear at the range of 6.25-100μg/mL and the correlation coefficient (r 2 ) values were >0.9811 for all matrices. The precision and accuracy of the method was determined by coefficient of variation (CV) and the relative standard deviation error (RSE), and both were less than 15%. Recovery ranged from 74.29 to 100.1% for carbofuran and from 64.72 to 100.61% for 3-hydroxycarbofuran. There were no significant interfering peaks or matrix effects. This method was suitable for detecting 25 positive cases for carbofuran amongst a total of 64 animal samples suspected of poisoning brought to the Toxicology Diagnostic Laboratory, School of Veterinary Medicine and Animal Sciences, University of Sao Paulo. Copyright © 2017 Elsevier B.V. All rights reserved.
Aim The aim of this study is to develop an understanding of the factors which influence veterinary surgeons’ clinical decision making during routine consultations. Methods The research takes a qualitative approach using video-cued interviews, in which one of the veterinary surgeon’s own consultations is used as the basis of a semi-structured interview exploring decision making in real cases. The research focuses primarily on small animal consultations in first opinion practice, how...
Wiggins, P.; Schenker, M.B.; Green, R.; Samuels, S.
All female graduates of a major U.S. veterinary school were surveyed by mailed questionnaire to obtain details of work practice and hazard exposure during the most recent year worked and during all pregnancies. Exposure questions were based on previously implicated occupational hazards which included anesthetic gases, radiation, zoonoses, prostaglandins, vaccines, physical trauma, and pesticides. The response rate was 86% (462/537). We found that practice type and pregnancy status were major determinants of hazard exposure within the veterinary profession. Small-animal practitioners reported the highest rates of exposure to anesthetic gas (94%), X-ray (90%), and pesticides (57%). Large-animal practitioners reported greater rates of trauma (64%) and potential exposure to prostaglandins (92%), Brucella abortus vaccine (23%), and carbon monoxide (18%). Potentially hazardous workplace practices or equipment were common. Forty-one percent of respondents who reported taking X-rays did not wear film badges, and 76% reported physically restraining animals for X-ray procedures. Twenty-seven percent of the respondents exposed to anesthetic gases worked at facilities which did not have waste anesthetic gas scavenging systems. Women who worked as veterinarians during a pregnancy attempted to reduce exposures to X-rays, insecticides, and other potentially hazardous exposures. Some potentially hazardous workplace exposures are common in veterinary practice, and measures to educate workers and to reduce these exposures should not await demonstration of adverse health effects.
Wiggins, P.; Schenker, M.B.; Green, R.; Samuels, S.
All female graduates of a major U.S. veterinary school were surveyed by mailed questionnaire to obtain details of work practice and hazard exposure during the most recent year worked and during all pregnancies. Exposure questions were based on previously implicated occupational hazards which included anesthetic gases, radiation, zoonoses, prostaglandins, vaccines, physical trauma, and pesticides. The response rate was 86% (462/537). We found that practice type and pregnancy status were major determinants of hazard exposure within the veterinary profession. Small-animal practitioners reported the highest rates of exposure to anesthetic gas (94%), X-ray (90%), and pesticides (57%). Large-animal practitioners reported greater rates of trauma (64%) and potential exposure to prostaglandins (92%), Brucella abortus vaccine (23%), and carbon monoxide (18%). Potentially hazardous workplace practices or equipment were common. Forty-one percent of respondents who reported taking X-rays did not wear film badges, and 76% reported physically restraining animals for X-ray procedures. Twenty-seven percent of the respondents exposed to anesthetic gases worked at facilities which did not have waste anesthetic gas scavenging systems. Women who worked as veterinarians during a pregnancy attempted to reduce exposures to X-rays, insecticides, and other potentially hazardous exposures. Some potentially hazardous workplace exposures are common in veterinary practice, and measures to educate workers and to reduce these exposures should not await demonstration of adverse health effects
Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C
Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.
Chang, Angela Y; Riumallo-Herl, Carlos; Perales, Nicole A; Clark, Samantha; Clark, Andrew; Constenla, Dagna; Garske, Tini; Jackson, Michael L; Jean, Kévin; Jit, Mark; Jones, Edward O; Li, Xi; Suraratdecha, Chutima; Bullock, Olivia; Johnson, Hope; Brenzel, Logan; Verguet, Stéphane
With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs' total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention.
Geels, Mark J; Thøgersen, Regitze L; Guzman, Carlos A; Ho, Mei Mei; Verreck, Frank; Collin, Nicolas; Robertson, James S; McConkey, Samuel J; Kaufmann, Stefan H E; Leroy, Odile
TRANSVAC was a collaborative infrastructure project aimed at enhancing European translational vaccine research and training. The objective of this four year project (2009-2013), funded under the European Commission's (EC) seventh framework programme (FP7), was to support European collaboration in the vaccine field, principally through the provision of transnational access (TNA) to critical vaccine research and development (R&D) infrastructures, as well as by improving and harmonising the services provided by these infrastructures through joint research activities (JRA). The project successfully provided all available services to advance 29 projects and, through engaging all vaccine stakeholders, successfully laid down the blueprint for the implementation of a permanent research infrastructure for early vaccine R&D in Europe. Copyright © 2015. Published by Elsevier Ltd.
Full Text Available Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD, is a recently described form of apoptosis induced by a specific set of chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing irradiation and photodynamic therapy. The peculiar characteristic of ICD is the ability to favor recognition and elimination of dying tumor cells by phagocytes in association with the release of pro-inflammatory molecules (such as cytokines and high-mobility group box-1. While in vitro and animal models pointed to ICD as one of the molecular mechanisms mediating the clinical efficacy of some anticancer agents, it is hard to clearly demonstrate its contribution in cancer patients. Clinical evidence suggests that the induction of ICD alone is possibly not sufficient to fully subvert the immunosuppressive tumor microenvironment. However, interesting results from recent studies contemplate the exploitation of ICD for improving the immunogenicity of cancer cells to use them as an antigen cargo in the development of dendritic cell (DC vaccines. Herein, we discuss the effects of danger signals expressed or released by cancer cells undergoing ICD on the maturation and activation of immature and mature DC, highlighting the potential added value of ICD in adoptive immunotherapy protocols.
Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali
Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Yao, Peng Ju; Stephenson, Nicole; Foley, Janet E; Toussieng, Chuck R; Farver, Thomas B; Sykes, Jane E; Fleer, Katryna A
To determine incidence rates (IRs) and potential risk factors for owner-reported adverse events (AEs) following vaccination of dogs that did or did not receive a Leptospira vaccine. Observational, retrospective cohort study. 130,557 dogs. Electronic records of mobile veterinary clinics from June 2012 to March 2013 were searched to identify dogs that received ≥ 1 vaccine in a given visit. Signalment data, vaccinations received, medications administered, and owner-reported clinical signs consistent with AEs that developed ≤ 5 days after vaccination were recorded. Associations between potential risk factors and owner-reported AEs were evaluated by logistic regression analysis. The IR/10,000 dogs for owner-reported postvaccination AEs was 26.3 (95% CI, 23.6 to 29.2), whereas that for dogs that received a Leptospira vaccine alone or with other vaccines was 53.0 (95% CI, 42.8 to 64.9). Significant factors for increasing or decreasing risk of AEs were as follows: receiving a Leptospira vaccine (adjusted OR, 2.13), age at vaccination 1 to dogs), and IRs for these events did not differ significantly between dogs vaccinated with or without a Leptospira component. The overall IR for owner-reported postvaccination AEs was low. Results suggested vaccination against Leptospira (an organism that can cause fatal disease) is safe in the majority of cases, slightly increasing the risk of owner-reported AEs but not associated with a significant increase in hypersensitivity reactions, compared with other vaccinations administered.
Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J
Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.
The bulk of current HIV vaccine research is conducted within the infectious disease paradigm that has been very successful in developing vaccines against many other viral diseases. Different HIV vaccine concepts, based on the induction of neutralizing antibodies and/or cell mediated immunity, have been developed and clinically tested over the last 30 years, resulting in a few small successes and many disappointments. As new scientific knowledge is obtained, HIV vaccine concepts are constantly modified with the hope that the newly introduced tweaks (or paradigm drifts) will provide the solution to one of the most difficult challenges that modern biomedical research is confronting. Efficacy trials have been critical in guiding HIV vaccine development. However, from the five phase III efficacy trials conducted to date, only one (RV144) resulted in modest efficacy. The results from RV144 were surprising in many ways, including the identified putative correlates of protection (or risk), which did not include neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine challenge may very well come from approaches based on the current paradigm. However, at the same time, out-of-the-paradigm ideas should be systematically explored to complement the current efforts. New mechanisms are needed to identify and support the innovative research that will hopefully accelerate the development of an urgently needed HIV vaccine.
Katz, Mira L; Oldach, Benjamin R; Goodwin, Jennifer; Reiter, Paul L; Ruffin, Mack T; Paskett, Electra D
Human papillomavirus (HPV) vaccination rates do not meet the Healthy People 2020 objective of 80% coverage among adolescent females. We describe the development and initial feedback about an HPV vaccine comic book for young adolescents. The comic book is one component of a multilevel intervention to improve HPV vaccination rates among adolescents. Parents suggested and provided input into the development of a HPV vaccine comic book. Following the development of the comic book, we conducted a pilot study to obtain initial feedback about the comic book among parents (n = 20) and their adolescents ages 9 to 14 (n = 17) recruited from a community-based organization. Parents completed a pre-post test including items addressing HPV knowledge, HPV vaccine attitudes, and about the content of the comic book. Adolescents completed a brief interview after reading the comic book. After reading the comic book, HPV knowledge improved (2.7 to 4.6 correct answers on a 0-5 scale; p book's content was acceptable and adolescents liked the story, found it easy to read, and thought the comic book was a good way to learn about being healthy. Parents provided valuable information in the development of a theoretically-based comic book and the comic book appears to be an acceptable format for providing HPV vaccine information to adolescents. Future research will include the comic book in an intervention study to improve HPV vaccination rates.
Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W
In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age 60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (Pvaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.
Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng
Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840
According to the IFAH, veterinary vaccines currently account for 26% of the global market in veterinary medicines, reflecting the importance of vaccines in animal health, as well as the number of wild and domesticated target species, and the monospecific nature of most vaccines. Multispecies vaccines include tetanus and rabies. In 2010, the number of food-producing animals was estimated to be roughly 20 billion and is rising gradually. Fowl currently represent the main food species. Veterinary vaccination has allowed the eradication of rinderpest, as officially declared last year (2011), jointly by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation of the United Nations (FAO). Rinderpest was a real scourge, and was only the second viral disease to be totally eradicated (after human smallpox). One characteristic of veterinary vaccination is the DIVA approach, "differentiating infected from vaccinated animals". The DIVA strategy is especially interesting for regulated control of diseases like foot-and-mouth disease, infectious bovine rhinotracheitis, pseudorabies, and classical swine fever. DIVA vaccination requires prior serological testing. Vaccination is also used for wild animals such as foxes (rabies) and wild boars (classical swine fever). "In ovo" vaccination of fowl on day 18 of the incubation period is used to prevent Marek's disease for instance, and double vaccination (vector and insert) to prevent both Marek's disease and Gumboro's disease in fowl. Animal vaccination can also help to protect human health, as illustrated by fowl vaccination against salmonellosis.
compared using univariate and logistic regression analyses to identify factors associated with vaccination ... reverse transcriptase- Polymerase chain ... Individuals at risk of rabies virus infection ..... vaccine supply in Nigerian hospitals might.
Full Text Available Attenuated yellow fever (YF virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE, aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.
Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T A; Dhalia, Rafael
Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.
Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T. A.; Dhalia, Rafael
Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. PMID:25875109
Karczewski, Jerzy; Zorman, Julie; Wang, Su; Miezeiewski, Matthew; Xie, Jinfu; Soring, Keri; Petrescu, Ioan; Rogers, Irene; Thiriot, David S; Cook, James C; Chamberlin, Mihaela; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Bodmer, Jean-Luc; Heinrichs, Jon H; Secore, Susan
Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hoffman, Stephen L; Billingsley, Peter F; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Li, Minglin; Stafford, Richard; Ahumada, Adriana; Epstein, Judith E; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L; Lyke, Kirsten E; Edelman, Robert; Laurens, Matthew B; Plowe, Christopher V; Sim, B Kim Lee
Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.
New approaches for vaccination must be developed in order to meet the grand challenges for emerging infectious diseases. Exosomes now enter vaccine development and these are strategies are meeting these global challenges, as demonstrated by Anticoli et al., in this issue of Biotechnology Journal. Using exosome vaccines has been now been demonstrated in vivo for several viruses such as Ebola Virus VP24, VP40, and NP, Influenza Virus NP, Crimean-Congo Hemorrhagic Fever NP, West Nile Virus NS3, and Hepatitis C Virus NS3. Now this technology must be tested in clinics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D
Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452
SUMMARY. In spite of numerous vaccines and different vaccination schedules used in the control of. Newcastle disease (ND), prevention and control remain a challenge. This study evaluated three different ND vaccines. A total of one hundred and twenty, day-old brown pullets obtained from a commercial hatchery in ...
Mamo, Laura; Epstein, Steven
Vaccine development is a core component of pharmaceutical industry activity and a key site for studying pharmaceuticalization processes. In recent decades, two so-called cancer vaccines have entered the U.S. medical marketplace: a vaccine targeting hepatitis B virus (HBV) to prevent liver cancers and a vaccine targeting human papillomavirus (HPV) to prevent cervical and other cancers. These viruses are two of six sexually transmissible infectious agents (STIs) that are causally linked to the development of cancers; collectively they reference an expanding approach to apprehending cancer that focuses attention simultaneously "inward" toward biomolecular processes and "outward" toward risk behaviors, sexual practices, and lifestyles. This paper juxtaposes the cases of HBV and HPV and their vaccine trajectories to analyze how vaccines, like pharmaceuticals more generally, are emblematic of contemporary pharmaceuticalization processes. We argue that individualized risk, in this case sexual risk, is produced and treated by scientific claims of links between STIs and cancers and through pharmaceutical company and biomedical practices. Simultaneous processes of sexualization and pharmaceuticalization mark these cases. Our comparison demonstrates that these processes are not uniform, and that the production of risks, subjects, and bodies depends not only on the specificities of vaccine development but also on the broader political and cultural frames within which sexuality is understood. Copyright © 2013 Elsevier Ltd. All rights reserved.
Chandra, Dheeraj; Kumar, Dinesh
In recent years, demand to improve child immunization coverage globally, and the development of the latest vaccines and technology has made the vaccine market very complex. The rise in such complexities often gives birth to numerous issues in the vaccine supply chain, which are the primary cause of its poor performance. Figuring out the cause of the performance problem can help you decide how to address it. The goal of the present study is to identify and analyze important issues in the supply chain of basic vaccines required for child immunization in the developing countries. Twenty-five key issues as various factors of the vaccine supply chain have been presented in this paper. Fuzzy MICMAC analysis has been carried out to classify the factors based on their driving and dependence power and to develop a hierarchy based model. Further, the findings have been discussed with the field experts to identify the critical factors. Three factors: better demand forecast, communication between the supply chain members, and proper planning and scheduling have been identified as the critical factors of vaccine supply chain. These factors should be given special care to improve vaccine supply chain performance.
Msellati, L; Commault, J; Dehove, A
Good veterinary governance assumes the provision of veterinary services that are sustainably financed, universally available, and provided efficiently without waste or duplication, in a manner that is transparent and free of fraud or corruption. Good veterinary governance is a necessary condition for sustainable economic development insomuch as it promotes the effective delivery of services and improves the overall performance of animal health systems. This article defines governance in Veterinary Services and proposes a framework for its measurement. It also discusses the role of Veterinary Services and analyses the governance dimensions of the performance-assessment tools developed by the World Organisation for Animal Health (OIE). These tools (OIE PVS Tool and PVS Gap Analysis) track the performance of Veterinary Services across countries (a harmonised tool) and over time (the PVS Pathway). The article shows the usefulness of the OIE PVS Tool for measuring governance, but also points to two shortcomings, namely (i) the lack of clear outcome indicators, which is an impediment to a comprehensive assessment of the performance of Veterinary Services, and (ii) the lack of specific measures for assessing the extent of corruption within Veterinary Services and the extent to which demand for better governance is being strengthened within the animal health system. A discussion follows on the drivers of corruption and instruments for perception-based assessments of country governance and corruption. Similarly, the article introduces the concept of social accountability, which is an approach to enhancing government transparency and accountability, and shows how supply-side and demand-side mechanisms complement each other in improving the governance of service delivery. It further elaborates on two instruments--citizen report card surveys and grievance redress mechanisms--because of their wider relevance and their possible applications in many settings, including Veterinary
Chen, Tzer-Shyong; Chen, Tzer-Long; Chung, Yu-Fang; Huang, Yao-Min; Chen, Tao-Chieh; Wang, Huihui; Wei, Wei
Pet markets involve in great commercial possibilities, which boost thriving development of veterinary hospital businesses. The service tends to intensive competition and diversified channel environment. Information technology is integrated for developing the veterinary hospital cloud service platform. The platform contains not only pet medical services but veterinary hospital management and services. In the study, QR Code andcloud technology are applied to establish the veterinary hospital cloud service platform for pet search by labeling a pet's identification with QR Code. This technology can break the restriction on veterinary hospital inspection in different areas and allows veterinary hospitals receiving the medical records and information through the exclusive QR Code for more effective inspection. As an interactive platform, the veterinary hospital cloud service platform allows pet owners gaining the knowledge of pet diseases and healthcare. Moreover, pet owners can enquire and communicate with veterinarians through the platform. Also, veterinary hospitals can periodically send reminders of relevant points and introduce exclusive marketing information with the platform for promoting the service items and establishing individualized marketing. Consequently, veterinary hospitals can increase the profits by information share and create the best solution in such a competitive veterinary market with industry alliance.
Soon after HIV was discovered as the cause of AIDS in 1983-1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.
Durando, Paolo; Iudici, Rocco; Alicino, Cristiano; Alberti, Marisa; de Florentis, Daniela; Ansaldi, Filippo; Icardi, Giancarlo
Vaccination is universally considered as the principal measure for the control of influenza, which represents a significant burden worldwide, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted trivalent influenza vaccines (TIVs) have been recognized as having some deficiencies, such as suboptimal immunogenicity particularly in the elderly, in patients with severe chronic diseases and immunocompromized, indeed, those groups of the population at higher risk of developing severe complications following influenza infection, when compared to healthy adults. Moreover, the protection offered by conventional vaccines may be reduced by periodic antigenic drifts, resulting in a mismatch between the circulating and vaccinal viral strains. Another gap regarding currently available vaccines is related to the egg-based manufacturing system for their production: not only the length of time involved with the latter but also the limited capacity of this platform technology represent a major limitation for the active prevention of influenza, which is particularly important in the case of a new pandemic strain. New technologies used in vaccine composition, administration and manufacture have led to major advances during the last few years, and clinical researchers have continued to work hard, investigating several different strategies to improve the performance of influenza vaccines: namely, the addition of different adjuvants (i.e., MF59- and AS03-vaccines, virosomal formulations), the use of alternative routes of administration or manufacture (i.e., intradermal, nasal and oral vaccines and cell culture- and reverse genetic-based vaccines) or of high doses of antigen, and the development of DNA-vaccines, or the use of conserved viral epitopes (i.e., the extracellular portion of the M2 protein, the nucleoprotein and some domains of the hemagglutinin), in the attempt to produce a "universal target" antigen vaccine. The knowledge acquired represents a
Daniels, Peter; Poermadjaja, Bagoes; Morrissy, Chris; Ngo, Thanh Long; Selleck, Paul; Kalpravidh, Wantanee; Weaver, John; Wong, Frank; Torchetti, Mia Kim; Allen, John; Padungtod, Parwin; Davis, Andrew; Suradhat, Sanipa; Morzaria, Subhash
The outbreak of highly pathogenic H5N1 avian influenza, with its international spread, confirmed that emerging infectious disease control must be underpinned by effective laboratory services. Laboratory results are the essential data underpinning effective surveillance, case diagnosis, or monitoring of responses. Importantly, laboratories are best managed within national and international networks of technological support rather than in isolation. A well planned laboratory network can deliver both a geographical spread of testing capacity and also a cost effective hierarchy of capability. Hence in the international context regional networks can be particularly effective. Laboratories are an integral part of a country's veterinary services and their role and function should be clearly defined in the national animal health strategy and supporting government policies. Not every laboratory should be expected to deliver every possible service, and integration into regional and broader international networks should be a part of the overall strategy. The outputs required of each laboratory should be defined and then ensured through accredited quality assurance. The political and scientific environment in which laboratories operate changes continuously, not only through evolving national and regional animal health priorities but also through new test technologies and enhancements to existing technologies. Active networks help individual laboratories to monitor, evaluate, and respond to such challenges and opportunities. The end result is enhanced emerging infectious disease preparedness across the region.
Pehrson, Caroline; Salanti, Ali; Theander, Thor G
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...
Brelsford, Jill B.; Plieskatt, Jordan L.; Yakovleva, Anna; Jariwala, Amar; Keegan, Brian P.; Peng, Jin; Xia, Pengjun; Li, Guangzhao; Campbell, Doreen; Periago, Maria Victoria; Correa-Oliveira, Rodrigo; Bottazzi, Maria Elena; Hotez, Peter J.
A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2–8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines. PMID:28192438
Jill B Brelsford
Full Text Available A new generation of vaccines for the neglected tropical diseases (NTDs have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus, so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2-8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.
Gottlieb, Sami L; Giersing, Birgitte; Boily, Marie-Claude; Chesson, Harrell; Looker, Katharine J; Schiffer, Joshua; Spicknall, Ian; Hutubessy, Raymond; Broutet, Nathalie
Development of a vaccine against herpes simplex virus (HSV) is an important goal for global sexual and reproductive health. In order to more precisely define the health and economic burden of HSV infection and the theoretical impact and cost-effectiveness of an HSV vaccine, in 2015 the World Health Organization convened an expert consultation meeting on HSV vaccine impact modelling. The experts reviewed existing model-based estimates and dynamic models of HSV infection to outline critical future modelling needs to inform development of a comprehensive business case and preferred product characteristics for an HSV vaccine. This article summarizes key findings and discussions from the meeting on modelling needs related to HSV burden, costs, and vaccine impact, essential data needs to carry out those models, and important model components and parameters. Copyright © 2017. Published by Elsevier Ltd.
Coleman, Jeffrey L; Shukla, Deepak
Despite recent advances in vaccine design and strategies, latent infection with herpes simplex virus (HSV) remains a formidable challenge. Approaches involving live-attenuated viruses and inactivated viral preparations were popular throughout the twentieth century. In the past ten years, many vaccine types, both prophylactic or therapeutic, have contained a replication-defective HSV, viral DNA or glycoproteins. New research focused on the mechanism of immune evasion by the virus has involved developing vaccines with various gene deletions and manipulations combined with the use of new and more specific adjuvants. In addition, new "prime-boost" methods of strengthening the vaccine efficacy have proven effective, but there have also been flaws with some recent strategies that appear to have compromised vaccine efficacy in humans. Given the complicated lifecycle of HSV and its unique way of spreading from cell-to-cell, it can be concluded that the development of an ideal vaccine needs new focus on cell-mediated immunity, better understanding of the latent viral genome and serious consideration of gender-based differences in immunity development among humans. This review summarizes recent developments made in the field and sheds light on some potentially new ways to conquer the problem including development of dual-action prophylactic microbicides that prohibit viral entry and, in addition, induce a strong antigen response.
Ohimain, Elijah Ige
Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.
Roč. 20, č. 1 (2002), s. 207-212 ISSN 1019-6439 Institutional research plan: CEZ:AV0Z5052915 Keywords : human papilloma viruses * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.931, year: 2002
Groot, Noortje; Heijstek, Marloes W.; Wulffraat, NM
In 2011, the European League Against Rheumatism (EULAR) published recommendations regarding the vaccination of children with rheumatic diseases. These recommendations were based on a systematic literature review published in that same year. Since then, the evidence body on this topic has grown
N. Groot (Noortje); M.W. Heijstek (Marloes); N.M. Wulffraat (Nico)
textabstractIn 2011, the European League Against Rheumatism (EULAR) published recommendations regarding the vaccination of children with rheumatic diseases. These recommendations were based on a systematic literature review published in that same year. Since then, the evidence body on this topic has
In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...
The antigen was clarified by simple centrifugation, adjuvated with saponin and aluminium hydroxide gel and 3 ml dose was used to vaccinate animals. The gel was prepared by simple procedure that required no special installation. No advise effects were observed in inoculated calves following 2-3 doses of the antigen in ...
Gwaltney-Brant, S M
Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.
Hrusovsky, J.; Benes, J.
A textbook is presented for pregraduate and postgraduate students of veterinary medicine, offering an extensive review of all aspects of radiology as applied in veterinary sciences. Based on findings published in the literature and the authors' own research, the textbook familiarizes the reader with the problems of nuclear physics, biological effects of ionizing radiation on animals, the principles of biological cycles of radionuclides in the atmosphere, the fundamentals of radiochemistry, dosimetry, radiometry and nuclear medicine. Radiation protection of animals, raw materials, feeds, foodstuff and water, and the questions of the aplications of ionizing radiation and of radionuclides in veterinary medicine are discussed in great detail. The publication is complemented with numerous photographs, figures and graphs. (L.O.)
Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa
BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...... for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP......). CONCLUSIONS: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well...
Johnston, C; Coffey, A; Sleator, RD
Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne disease, a granulomatous enteritis of cattle and other domesticated and wild ruminant species. Johne disease is prevalent worldwide and has a significant impact on the global agricultural economy. Current vaccines against Johne are insufficient in stemming its spread, and associated side-effects prevent their widespread use in control programs. Effective and safe vaccine strategies are needed. The main purpose of this paper is to propose and evaluate the development of a novel oral subunit-vaccine using a patho-biotechnological approach. This novel strategy, which harnesses patho-genetic elements from the intracellular pathogen Listeria monocytogenes, may provide a realistic route towards developing an effective next generation subunit vaccine against Johne disease and paratuberculosis. PMID:21326921
Rosales-Mendoza, Sergio; Nieto-Gómez, Ricardo; Angulo, Carlos
The Ebola virus (EBOV) epidemic indicated a great need for prophylactic and therapeutic strategies. The use of plants for the production of biopharmaceuticals is a concept being adopted by the pharmaceutical industry, with an enzyme for human use currently commercialized since 2012 and some plant-based vaccines close to being commercialized. Although plant-based antibodies against EBOV are under clinical evaluation, the development of plant-based vaccines against EBOV essentially remains an unexplored area. The current technologies for the production of plant-based vaccines include stable nuclear expression, transient expression mediated by viral vectors, and chloroplast expression. Specific perspectives on how these technologies can be applied for developing anti-EBOV vaccines are provided, including possibilities for the design of immunogens as well as the potential of the distinct expression modalities to produce the most relevant EBOV antigens in plants considering yields, posttranslational modifications, production time, and downstream processing. PMID:28344580
Camilla Kirketerp Nielsen
Full Text Available The overall objective of this project is research-based development, implementation and evaluation of a game-based learning concept to be used in the veterinary education. Herd visits and animal contact are essential for the development of veterinary competences and skills during education. Yet veterinary students have little occasion to reach/attain a proper level of confidence in their own skills/abilities, as they have limited “training-facilities” (Kneebone & Baillie, 2008. One possible solution mightbe to provide a safe, virtual environment (game-based where students could practise interdisciplinary clinical skills in an easily-accessible, interactive setting. A playable demo using Classical Swine Fever in a pig herd as an example has been produced for this purpose. In order totailor the game concept to the specific veterinary learning environment and to ensure compliance with both learning objectives and the actual learning processes/procedures of the veterinary students, the project contains both a developmental aspect (game development and an exploration of the academic (scholastic and profession (practice oriented learning context. The initial phase of the project was a preliminary exploration of the actual learning context, providing an important starting point for the upcoming phase in which I will concentrate on research-based development, implementation and evaluation of a game-based virtual environment in this course context. In the academic (scholastic and profession (practice oriented learning context of a veterinary course in Herd Health Management (Pig module,ethnographic studies have been conducted by using multiple data collection methods; participant observation, spontaneous dialogues and interviews (Borgnakke, 1996; Hammersley & Atkinson, 2007. All courserelated activities in the different learning spaces (commercial pig herds, auditoriums, post-mortem examinations, independent group work were followed.This paper will
vaccines, ionizing radiation (IR)-induced destruction of a virus’ genome is desired, while radiation - induced damage to epitopes is...development of irradiation-based approaches to vaccine production [1-3]. During ionizing radiation (IR) exposure, the energy of the photons induces direct...specifically protect proteins from the far more damaging indirect effects of gamma (γ)-rays in aqueous preparations. Mn2+-peptide antioxidants that
Gregory, Michael; Kaminski, Robert W.; Lugo-Roman, Luis A.; Galvez Carrillo, Hugo; Tilley, Drake Hamilton; Baldeviano, Christian; Simons, Mark P.; Reynolds, Nathanael D.; Ranallo, Ryan T.; Suvarnapunya, Akamol E.; Venkatesan, Malabi M.; Oaks, Edwin V.
Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have...
Plotkin, Stanley A; Plotkin, Susan L
The history of vaccine development has seen many accomplishments, but there are still many diseases that are difficult to target, and new technologies are being brought to bear on them. Past successes have been largely due to elicitation of protective antibodies based on predictions made from the study of animal models, natural infections and seroepidemiology. Those predictions have often been correct, as indicated by the decline of many infections for which vaccines have been made over the past 200 years.
Kallfelz, F.A.; Comar, C.L.; Wentworth, R.A.
A brief review is presented of the expanding horizons of nuclear medicine, the equipment necessary for a nuclear medicine laboratory is listed, and the value of this relatively new field to the veterinary clinician is indicated. Although clinical applications to veterinary medicine have not kept pace with those of human medicine, many advances have been made, particularly in the use of in vitro techniques. Areas for expanded applications should include competitive protein binding and other in vitro procedures, particularly in connection with metabolic profile studies. Indicated also is more intensive application by the veterinarian of imaging procedures, which have been found to be of such great value to the physician. (U.S.)
Baars, J C
Veterinary medicines constitute an unescapable element in the scheme of animal health and welfare. Nowadays, they are used more and more to improve health and productivity in farm animals. When a veterinary medicine is prescribed it must not only be effective but must also be safe for both animals and humans. Due to ever changing regulations and constant improvements in residue detection techniques it is necessary to conduct new investigations with existing products. It therefore costs a great deal of time and money to introduce, and maintain, a product in the market. In future, therefore, fewer medicines with more limited indications will be introduced and these will be to combat important production disorders in the more significant species only. In view of the above, research and production will be restricted to large, international, concerns. Due to our well structured agricultural industry and the existence of well organized and equipped veterinary research institutions, and practitioners, Holland is able to play an important role in the development of veterinary medicines. Close co-operation between all involved parties coupled with an efficient registration procedure is not ony of benefit to the veterinary pharmaceutical industry but also for international recognition of our national animal husbandry industry, ancillary industries and veterinary and other consultants. In this scheme of things the accent is not upon qualifications but upon the skills of veterinarians - wherever placed - who are involved in the administration of veterinary medicines.
Valencia-Mendoza, Atanacio; Bertozzi, Stefano M; Gutierrez, Juan-Pablo; Itzler, Robbin
Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be
Full Text Available Abstract Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%, 5,040 hospital admissions (66%, and 612 deaths from rotavirus gastroenteritis (70%. At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine
During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.
Mariana Costa Duarte
Full Text Available Abstract: Visceral leishmaniasis (VL is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insufficiently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control; for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses; however, their partial efficacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identified using immuno-proteomic techniques.
Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung
The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.
Henninger, Michelle L; Mcmullen, Carmit K; Firemark, Alison J; Naleway, Allison L; Henrikson, Nora B; Turcotte, Joseph A
Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and is associated with multiple types of cancer. Although effective HPV vaccines have been available since 2006, coverage rates in the US remain much lower than with other adolescent vaccinations. Prior research has shown that a strong recommendation from a clinician is a critical determinant in HPV vaccine uptake and coverage. However, few published studies to date have specifically addressed the issue of helping clinicians communicate more effectively with their patients about the HPV vaccine. To develop one or more novel interventions for helping clinicians make strong and effective recommendations for HPV vaccination. Using principles of user-centered design, we conducted qualitative interviews, interviews with persons from analogous industries, and a data synthesis workshop with multiple stakeholders. Five potential intervention strategies targeted at health care clinicians, youth, and their parents were developed. The two most popular choices to pursue were a values-based communication strategy and a puberty education workbook. User-centered design is a useful strategy for developing potential interventions to improve the rate and success of clinicians recommending the HPV vaccine. Further research is needed to test the effectiveness and acceptability of these interventions in clinical settings.
Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.
Volz, A; Sutter, G
Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.
García-Seco, Teresa; Pérez-Sancho, Marta; Salinas, Jesús; Navarro, Alejandro; Díez-Guerrier, Alberto; García, Nerea; Pozo, Pilar; Goyache, Joaquín; Domínguez, Lucas; Álvarez, Julio
Ovine enzootic abortion, caused by Chlamydia abortus, leads to important economic losses worldwide. In addition to reproductive failures, infection may impact lamb growth during the first weeks after birth, yet this effect has not been well characterized. Vaccination can help to control the disease but variable efficacy values have been described, possibly related with factors associated with the host, the vaccine, the parameter used for efficacy determination, and the challenge conditions. In this context, we evaluated the efficacy of an inactivated standard commercial vaccine and a 1/2 diluted dose in pregnant sheep challenged with C. abortus by examining multiple indicators of vaccine effect (including incidence of reproductive failures, bacterial excretion, and evolution of weight gain of viable lambs during the first month of life). Three groups of ewes [control non-vaccinated, C (n = 18); vaccinated with standard dose, SV (n = 16); and vaccinated with 1/2 dose, DV (n = 17)], were challenged approximately 90 days post-mating and tested using direct PCR (tissue samples and vaginal swabs) and ELISA (serum) until 31 days post-reproductive outcome. There were not significant differences in the proportions of reproductive failures or bacterial shedding after birth/abortion regardless the vaccination protocol. However, a beneficial effect of vaccination on offspring growth was detected in both vaccinated groups compared with the controls, with a mean increase in weight measured at 30 days of life of 1.5 and 2.5 kg (p = 0.056) and an increase in the geometric mean of the daily gain of 8.4 and 9.7% in lambs born from DV and SV ewes compared with controls, respectively. Our results demonstrate the effect of an inactivated vaccine in the development of the offspring of C. abortus-infected ewes at a standard and a diluted dose, an interesting finding given the difficulty in achieving sufficient antigen concentration in the production of enzootic
Hudak, R.; Zivcak, J.; Sevcik, A.; Danko, J.
The use of infrared thermography in veterinary medicine has been practiced since at least the 1960's, but it is only now, in approximately the last 5 years, that it has been viewed with a reasonably open mind in the veterinary community at large. One of the reasons is progress in sensors technology, which contributed for an outstanding improvement of the thermal imager parameters. Paper deals with veterinary thermography and with description of applications at the University of Veterinary Medicine in Kosice. (authors)
Liang, Yan; Ma, Shaohui; Liu, Longding; Zhao, Hongling; Wang, Lichun; Jiang, Li; Xie, Zhongping; Dong, Chenghong; Li, Qihan
Mumps epidemics are usually caused by airborne transmission of mumps virus (MuV) and have high morbidity in non-immunized children. Epidemiological studies in many regions of China show that the genotype F viral strain is the most prevalent. However, the genotype A strain is currently used to prepare vaccines. Regional epidemiological MuV data suggest a significant application for the development of live attenuated mumps vaccines targeting specific genotypes. This article reports the isolation and culture of a genotype F MuV candidate strain that could be used to prepare a live attenuated mumps vaccine. This strain is shown to have good immunological efficacy and stability in neurovirulence evaluations. This work should facilitate the implementation of mumps vaccination in mainland China by targeting the most prevalent MuV genotype, genotype F. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.
McNiel, E A
Epidemiologic evidence supports a relationship between vaccination of cats for rabies and feline leukemia virus with the development of soft tissue sarcomas at the site of administration. These tumors are locally invasive and histologically aggressive. As with high-grade soft tissue sarcoma in humans, combination treatment with radiation therapy and surgery provides for optimum tumor control. Feline vaccine-associated sarcoma has become a difficult issue for the veterinary profession for legal, ethical, and clinical reasons. Although most research efforts have focused on therapeutic intervention, this tumor has great potential to provide an informative model for carcinogenesis and genetic susceptibility applicable to cancer in all species, including humans.
Isabel N. Kantor
Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjec...
Abdul Hafid, Sitti Rahma; Radhakrishnan, Ammu Kutty; Nesaretnam, Kalanithi
Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy
Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.
Smith, Larry R; Wloch, Mary K; Chaplin, Jennifer A; Gerber, Michele; Rolland, Alain P
2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.
Davis, Courtney L.; Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.
We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design. PMID:23589755
Journal Homepage Image. Zimbabwe Veterinary Journal contains original and review papers on all aspects of animal health in Zimbabwe and SADC countries, including articles by non-veterinarians. This journal did not publish any issues between 2002 and 2015 but has been revived and and it actively accepting papers ...
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Bull, Tim J; Gilbert, Sarah C; Sridhar, Saranya; Linedale, Richard; Dierkes, Nicola; Sidi-Boumedine, Karim; Hermon-Taylor, John
Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly
Song, Woo-Jin; Kim, Hyun-Tae; Yoo, Han-Sang; Youn, Hwa-Young
This guideline contains the recommended vaccination schedules of dogs and cats from World Small Animal Veterinary Association (WSAVA) and American Animal Hospital Association (AAHA). In 2010, WSAVA published guidelines for the vaccination of dogs and cats. And, in 2011, AAHA also published guidelines for vaccination of dogs. In Korea, there is no published guideline for vaccination of dogs and cats yet. Therefore, the plane of vaccination also reports the present situation of vaccination schedule of dogs and cats in Korean animal hospitals.
Song, Woo-Jin; Kim, Hyun-Tae; Yoo, Han-Sang; Youn, Hwa-Young
This guideline contains the recommended vaccination schedules of dogs and cats from World Small Animal Veterinary Association (WSAVA) and American Animal Hospital Association (AAHA). In 2010, WSAVA published guidelines for the vaccination of dogs and cats. And, in 2011, AAHA also published guidelines for vaccination of dogs. In Korea, there is no published guideline for vaccination of dogs and cats yet. Therefore, the plane of vaccination also reports the present situation of vaccination sche...
after multiple passages in vivo and in vitro. J. Gen. Virol. 67, 1741- 1744. Sabin , A.B. (1985). Oral poliovirus vaccine : history of its development...IN (N NEW APPROACHES TO ATTENUATED HEPATITIS A VACCINE DEVELOPMENT: Q) CLONING AND SEQUENCING OF CELL-CULTURE ADAPTED VIRAL cDNA I ANNUAL REPORT...6ll02Bsl0 A 055 11. TITLE (Include Security Classification) New Approaches to Attenuated Hepatitis A Vaccine Development: Cloning and Sequencing of Cell
Despite the evidence that the immune system plays a significant role in controlling tumor growth in natural conditions and in response to therapeutic vaccination, cancer cells can survive their attack as the disease progresses and no vaccination regimen should be currently proposed to patients outside experimental clinical trials. Clinical results show that the immune system can be actively polarized against malignant cells by means of a variety of vaccination strategies, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally "dormant" immune effectors can actually be put at work and used as endogenous weapons against malignant cells. Consequently, the main challenge of tumor immunologists appears to lie on the ability of reproducing those conditions in a larger set of patients. The complexity of the immune network and the still enigmatic host-tumor interactions make these tasks at the same time challenging and fascinating. Recent tumor immunology findings are giving new impetus to the development of more effective vaccination strategies and might revolutionize the way of designing the next generation of cancer vaccines. In the near future, the implementation of these insights in the clinical setting and the completion/conduction of comparative randomized phase III trials will allow oncologists to define the actual role of cancer vaccines in the fight against malignancy.
Kitagawa, Koichi; Oda, Tsugumi; Saito, Hiroki; Araki, Ayame; Gonoi, Reina; Shigemura, Katsumi; Hashii, Yoshiko; Katayama, Takane; Fujisawa, Masato; Shirakawa, Toshiro
Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4 + T and CD8 + T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.
Hashizume, Cary T; Woloschuk, Wayne; Hecker, Kent G
There is a paucity of research regarding veterinary students' attitudes toward the rural environment and rural veterinary practice and how these attitudes might change over the course of a veterinary medicine program that includes rural clinical experience. Using a 23-item questionnaire, attitudes toward rural lifestyle, rural work-life balance, opportunities for career and skill development in rural veterinary practice, and inter-professional teamwork in the rural environment were assessed at the beginning and completion of a four-year veterinary medicine program. Eighty-six students (74.4% female) were included in this Canadian study over a six-year period. Thirty-one participants (36.1%) were rural students. Overall, students' attitudes toward the rural lifestyle, rural work-life balance, and inter-professional teamwork in rural veterinary practice all significantly decreased (pstudents, rural students had significantly higher rural lifestyle scores at both the beginning (pworking in a rural environment could influence students to exclude rural veterinary practice as a career choice. Rural clinical experiences designed to sustain or increase veterinary student interest in rural practice may not be sufficient to support positive rural attitudes. Given the demand for rural veterinary services in developed countries, the implications of this study may extend beyond Canada.
Development of Radiometric and Allied Analytical Methods and Strategies to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues. Final Report of a Coordinated Research Project
Awareness of food safety is rising among consumers, and many importing countries implement food control regulations to guarantee the quality and safety of imported foods for their consumers. Many developing countries have also taken steps to put in place control systems that encourage responsible use of veterinary medicines to combat possible drug resistance, control drug residues and ensure compliance with international and national standards. However, these countries still require the necessary know-how and skills to protect local consumers and to access international markets. One significant constraint is the capacity of laboratory services to generate surveillance data using reliable and cost effective analytical methods validated to national and international standards. The IAEA coordinated research project (CRP) on the Development of Radiometric and Allied Analytical Methods to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues was initiated in 2009 to conduct work on robust nuclear and related technologies suitable for the screening and confirmatory analysis of residues of veterinary medicines, including antimicrobials and anthelmintics commonly used in animal production, with public health and trade significance. The CRP also explored mechanisms to enhance networking among research institutions involved in research on pharmacologically active veterinary drug residues in food (primarily) and environmental samples. The project was implemented by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture between 2009 and 2014 and involved eleven research contracts and one technical contract, five research agreements and one institution. The CRP was a continuation of the CRP on the Development of Strategies for the Effective Monitoring of Veterinary Drug Residues in Livestock and Livestock Products in Developing Countries and the key findings are also summarized in this publication.
Marc H. V. Van Regenmortel
Full Text Available Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly
Birk, Nina Marie; Nissen, Thomas Nørrelykke; Ladekarl, Monica
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact...... of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG...... vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence...
Full Text Available Background: In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options.Aim of the project: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM. Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic.Methods: According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives.Results: These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in
Day, M J; Karkare, U; Schultz, R D; Squires, R; Tsujimoto, H
In 2012 and 2013, the World Small Animal Veterinary Association (WSAVA) Vaccination Guidelines Group (VGG) undertook fact-finding visits to several Asian countries, with a view to developing advice for small companion animal practitioners in Asia related to the administration of vaccines to dogs and cats. The VGG met with numerous first opinion practitioners, small animal association leaders, academic veterinarians, government regulators and industry representatives and gathered further information from a survey of almost 700 veterinarians in India, China, Japan and Thailand. Although there were substantial differences in the nature and magnitude of the challenges faced by veterinarians in each country, and also differences in the resources available to meet those challenges, overall, the VGG identified insufficient undergraduate and postgraduate training in small companion animal microbiology, immunology and vaccinology. In most of the countries, there has been little academic research into small animal infectious diseases. This, coupled with insufficient laboratory diagnostic support, has limited the growth of knowledge concerning the prevalence and circulating strains of key infectious agents in most of the countries visited. Asian practitioners continue to recognise clinical infections that are now considered uncommon or rare in western countries. In particular, canine rabies virus infection poses a continuing threat to animal and human health in this region. Both nationally manufactured and international dog and cat vaccines are variably available in the Asian countries, but the product ranges are small and dominated by multi-component vaccines with a licensed duration of immunity (DOI) of only 1 year, or no description of DOI. Asian practitioners are largely unaware of current global trends in small animal vaccinology or of the WSAVA vaccination guidelines. Consequently, most practitioners continue to deliver annual revaccination with both core and non
Chadderdon, Linda M; Lloyd, James W; Pazak, Helene E
Veterinary technology has generally established itself well in companion-animal and mixed-animal veterinary medical practice, but the career's growth trajectory is uncertain. Michigan State University (MSU) convened a national conference, "Creating the Future of Veterinary Technology-A National Dialogue," in November 2011 to explore ways to elevate the veterinary technician/technologist's role in the veterinary medical profession and to identify new directions in which the career could expand. Veterinary technicians/technologists might advance their place in private practice by not only improving their clinical skills, but by also focusing on areas such as practice management, leadership training, business training, conflict resolution, information technology, and marketing/communications. Some new employment settings for veterinary technicians/technologists include more participation within laboratory animal medicine and research, the rural farm industry, regulatory medicine, and shelter medicine. Achieving these ends would call for new training options beyond the current 2-year and 4-year degree programs. Participants suggested specialty training programs, hybrid programs of various types, online programs, veterinary technician residency programs of 12-18 months, and more integration of veterinary technician/technology students and veterinary medicine students at colleges of veterinary medicine.
Full Text Available Vaccines developed from certain membrane proteins lining the lumen of arthropod’s gut have been demonstrated effective in the control of some arthropod ectoparasites. A similar approach could also be applied to Sarcoptes scabiei since this parasite also ingests its host immunoglobulins. To evaluate immune protection of the membrane proteins, insoluble mite proteins were fractionated by successive treatment in the solutions of 1.14 M NaCl, 2% SB 3-14 Zwitterion detergent, 6 M urea, 6 M guanidine-HCl and 5% SDS. Five groups of goats (6 or 7 goats per group were immunised respectively with the protein fractions. Vaccination was performed 6 times, each with a dosage of 250 μg proteins, and 3 week intervals between vaccination. Group 6 (7 goats received PBS and adjuvant only, and served as an unvaccinated control. One week after the last vaccination, all goats were challenged with 2000 live mites on the auricles. The development of lesions were examined at 1 day, 2 days, and then every week from week 1 to 8. All animals were bled and weighed every week, and at the end of the experiment, skin scrapings were collected to determine the mite burden. Antibody responses induced by vaccination and challenge were examined by ELISA and Western blotting. This experiment showed that vaccination with the insoluble-protein fractions resulted in the development of high level of specific antibodies but the responses did not have any protective value. The severity of lesions and mite burden in the vaccinated animals were not different from those in the unvaccinated control.
Response of a veterinary college to career development needs identified in the KPMG LLP study and the executive summary of the Brakke study: a combined MBA/DVM program, business certificate program, and curricular modifications.
Kogan, Lori R; McConnell, Sherry L; Schoenfeld-Tacher, Regina
In the present market, veterinarians with a strong background in career development, practice management, and business skills have a clear advantage in achieving financial success. Although there is ample evidence that the scientific and clinical skills of veterinary college graduates are high, there are also data that suggest that additional capabilities in the business realm may promote greater economic success. As noted in the KPMG executive summary, the field of veterinary medicine must make changes in its "current business practices and attitudes" to be successful in the future. Furthermore, the KPMG study found that 36% of industry employers reported that some jobs within their companies had specific job requirements that were not met by a veterinarian with only a veterinary medical degree. The areas of additional training most often cited included business, administration, personnel management, sales and marketing, and financial skills. Yet, Lewis and Klausner found that veterinarians reported challenges in the business realm, such as "how business works and how business goals are translated into action. This challenge held true for veterinarians in industry, academia, government, and private practice." The present gender trends in the field of veterinary medicine provide additional impetus to make career development and business skills training more prevalent. Presently, women comprise >65% of the veterinary student population and approximately 45% of all practicing veterinarians. In some areas of practice, the rate is much higher. For example, in 2002, women comprised 48.2% of all small animal exclusive private practitioners. Unfortunately, the KPMG study found that female veterinarians in private practice report lower self-evaluation of business management and financial skills, compared with their male cohorts. Female veterinarians in nonprivate practice report lower self-evaluation in communication, personnel management, business management, and
Matthews, J B; Geldhof, P; Tzelos, T; Claerebout, E
The global increase in anthelmintic resistant nematodes of ruminants, together with consumer concerns about chemicals in food, necessitates the development of alternative methods of control for these pathogens. Subunit recombinant vaccines are ideally placed to fill this gap. Indeed, they are probably the only valid option for the long-term control of ruminant parasitic nematodes given the increasing ubiquity of multidrug resistance in a range of worm species across the world. The development of a subunit multicellular parasite vaccine to the point of practical application would be a groundbreaking step in the control of these important endemic infections of livestock. This review summarizes the current status of subunit vaccine development for a number of important gastrointestinal nematodes of cattle and sheep, with a focus on the limitations and problems encountered thus far, and suggestions as to how these hurdles might be overcome. © 2016 John Wiley & Sons Ltd.
Smith, Donald F
The future of veterinary medicine is best understood in the context of history. What began as a profession rooted in urban centers in proximity to horses, physicians, and medical schools, was transformed into a land grant-based agricultural profession with the arrival of the internal combustion engine in the early twentieth century. Most of the United States' current veterinary colleges are still located in towns or small cities in the middle section of the country, outside the largest metropolitan areas where most veterinarians practice companion-animal medicine. Throughout veterinarian history, substantial numbers of US students have been educated in foreign colleges and this continues today, creating an even greater geographic imbalance between the veterinary educational process and US population centers and major medical schools. Three themes deserve special attention as we celebrate the profession's 150th anniversary. We must first move beyond the land-grant culture and develop a more geographically balanced approach to establishing new veterinary colleges that are also in closer association with schools of medicine and public health. We must also facilitate more opportunities for women leadership in organized veterinary medicine, in practice ownership, in academia, and in the corporate structures that educate, hire, and interface with veterinarians. Finally, we need to expand our understanding of One Health to include the concept of zooeyia (the role of animals in promoting human health), as well as continue to emphasize veterinarians' special roles in the control and management of zoonotic diseases and in advancing comparative medicine in the age of the genome.
Page-Jones, S; Abbey, G
This research investigates vet and vet nurse career identity through the qualitative methodology of narrative enquiry. It derives learning and understanding from these empirical data to assist the veterinary profession to adjust to the changing industry landscape. Through a case series of 20 vets and vet nurses' career stories, this paper seeks understanding about career identity and its impact on individuals and organisations in the light of industry consolidation. Findings suggest that career is central to identity for many veterinary professionals who tend to have a strong sense of self; this is particularly evident around self as learner and technically competent, teacher and educator, ethical and moral and dedicated and resilient. Consequently, mismatches between 'who I am' and 'what I do' tend not to lead to identity customisation (to fit self into role or organisation) but to the search for alternative, more identity-compatible employment. This study offers a valuable insight for employers, veterinary professionals and universities. It suggests that businesses can gain competitive advantage and employees achieve validation and enrichment by working towards organisational and individual identity congruence and that teaching veterinary professionals with contemporary business in mind may develop graduates with a more sustainable identity. British Veterinary Association.
Full Text Available Visceral Leishmaniasis (VL or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that nearly 500,000 new cases of VL occur annually, including 100,000 cases from India itself. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era i.e. from genomics to immunomics. Classical as well as molecular methodologies has been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL.
Stevenson, Michael A
Vaccines were once produced almost exclusively by state-supported entities. While they remain essential tools for public health protection, the majority of the world's governments have allowed industry to assume responsibility for this function. This is significant because while the international harmonisation of quality assurance standards have effectively increased vaccine safety, they have also reduced the number of developing country vaccine producers, and Northern multinational pharmaceutical companies have shown little interest in offering the range of low-priced products needed in low and middle-income-country contexts. This article examines how public-private collaboration is relevant to contemporary efforts aimed at strengthening developing country manufacturers' capacity to produce high-quality, low-priced vaccines. Specifically, it casts light on the important and largely complimentary roles of the World Health Organization, The Bill and Melinda Gates Foundation, and the Seattle-based non-profit PATH, in this process. The take away message is that external support remains critical to ensuring that developing country vaccine manufacturers have the tools needed to produce for both domestic and global markets, and the United Nations supply chain, and collaboration at the public-private interface is driving organisational innovation focused on meeting these goals.
The Third Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the Ninth International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on August 18, 2020. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialisation an...
Vockeroth, W G
Complementary and alternative therapies, including homeopathy, have a definite place in veterinary medicine today. The public is demanding access to a full range of conventional and complementary therapies, and the best scenario is to have all therapies available, for there is a place and a need for all of them in the right situation. In my own practice, I use both alternative and conventional therapies, as well as referring patients to specialists, for services such as ultrasound and surgery...
To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resi...
Truszczyński, M J
Veterinary laboratories which deal with infectious diseases form three groups according to the tasks for which they are responsible. The first group includes central or national veterinary laboratories, national or international reference laboratories, high-security laboratories, district regional or state veterinary diagnostic laboratories. The major role of these laboratories is to assist national Veterinary Services in diagnosing infectious animal diseases. The second group comprises laboratories that produce veterinary diagnostic kits and those that produce veterinary vaccines. The third group is composed of veterinary research laboratories, which generally concentrate on basic research and do not contribute directly to the diagnosis and control of infectious animal diseases. The author describes the objectives of each of the three groups of laboratories.
Lin, Tzu-Yin; Rodriguez, Carlos O; Li, Yuanpei
Nanomedicine is an interdisciplinary field that combines medicine, engineering, chemistry, biology and material sciences to improve disease management and can be especially valuable in oncology. Nanoparticle-based agents that possess functions such as tumor targeting, imaging and therapy are currently under intensive investigation. This review introduces the basic concept of nanomedicine and the classification of nanoparticles. Because of their favorable pharmacokinetics, tumor targeting properties, and resulting superior efficacy and toxicity profiles, nanoparticle-based agents can overcome several limitations associated with conventional diagnostic and therapeutic protocols in veterinary oncology. The two most important tumor targeting mechanisms (passive and active tumor targeting) and their dominating factors (i.e. shape, charge, size and nanoparticle surface display) are discussed. The review summarizes published clinical and preclinical studies that utilize different nanoformulations in veterinary oncology, as well as the application of nanoparticles for cancer diagnosis and imaging. The toxicology of various nanoformulations is also considered. Given the benefits of nanoformulations demonstrated in human medicine, nanoformulated drugs are likely to gain more traction in veterinary oncology. Published by Elsevier Ltd.
Magalhães-Sant'Ana, Manuel; Lassen, Jesper; Millar, Kate M; Sandøe, Peter; Olsson, I Anna S
Although it is widely agreed that veterinary students need to be introduced to ethics, there is limited empirical research investigating the reasons why veterinary ethics is being taught. This study presents the first extensive investigation into the reasons for teaching veterinary ethics and reports data collected in semi-structured interviews with educators involved in teaching undergraduate veterinary ethics at three European schools: the University of Copenhagen, the University of Nottingham, and the Technical University of Lisbon (curricular year 2010-2011). The content of the interview transcripts were analyzed using Toulmin's argumentative model. Ten objectives in teaching veterinary ethics were identified, which can be grouped into four overarching themes: ethical awareness, ethical knowledge, ethical skills, and individual and professional qualities. These objectives include recognizing values and ethical viewpoints, identifying norms and regulations, developing skills of communication and decision making, and contributing to a professional identity. Whereas many of the objectives complement each other, there is tension between the view that ethics teaching should promote knowledge of professional rules and the view that ethics teaching should emphasize critical reasoning skills. The wide range of objectives and the possible tensions between them highlight the challenges faced by educators as they attempt to prioritize among these goals of ethics teaching within a crowded veterinary curriculum.
Moore, Irene C; Coe, Jason B; Adams, Cindy L; Conlon, Peter D; Sargeant, Jan M
To determine the role of veterinary team effectiveness regarding job satisfaction and burnout in companion animal veterinary practice. Cross-sectional observational study. 48 companion animal veterinary health-care teams. 274 team members participated in an online survey. Overall job satisfaction was evaluated with a 1-item measure, and the 3 dimensions of burnout (exhaustion, cynicism, and professional efficacy) were measured with the Maslach Burnout Inventory-General Survey. Team effectiveness was assessed with a survey developed for this study. Demographic and team effectiveness factors (coordinated team environment, toxic team environment, team engagement, and individual engagement) associated with job satisfaction and burnout were evaluated. Overall mean job satisfaction score was 5.46 of 7 (median, 6.00); veterinary technicians and kennel attendants had the lowest scores. According to the Maslach survey results, 22.4% of participants were in the high-risk category for exhaustion, 23.2% were in the high-risk category for cynicism, and 9.3% were in the high-risk category for professional efficacy. A coordinated team environment was associated with increased professional efficacy and decreased cynicism. A toxic team environment was negatively associated with job satisfaction and positively associated with exhaustion and cynicism. Individual engagement was positively associated with job satisfaction and professional efficacy and negatively associated with exhaustion and cynicism. Results suggested the effectiveness of a veterinary team can significantly influence individual team members' job satisfaction and burnout. Practices should pay specific attention to the effectiveness with which their veterinary team operates.
Hirth, Jacqueline M; Batuuka, Denise N; Gross, Tyra T; Cofie, Leslie; Berenson, Abbey B
Previous interventions in colleges to improve human papillomavirus (HPV) vaccination have not been highly successful. Although barriers have been assessed in traditional colleges, less is known about vaccination barriers in community colleges. We approached students aged 18-26 years old enrolled at a community college for an in-person semi-structured qualitative interview on HPV vaccination and health, with questions guided by the Theory of Planned Behavior. Data collection took place between April 2015 and December 2015. Thematic analysis techniques were used to analyze the data. During interviews with 19 students, 4 themes emerged, including: general vaccine attitudes, barriers to HPV vaccination, motivators to HPV vaccination, and social influences. Participants felt that vaccines were beneficial, but were concerned about side effects. They felt that getting the HPV vaccine would be inconvenient, and they did not know enough about it to decide. Most would not trust their friends' opinions, but would want to know about side effects that their vaccinated friends experienced. Successful interventions at community colleges should include several components to increase convenience as well as utilize interactive methods to promote HPV vaccine awareness. Copyright © 2018. Published by Elsevier Ltd.
Full Text Available 2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB and phosphoprotein 65 (pp65 formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV+ recipients of an allogeneic hematopoietic stem cell transplant (HCT. A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV+ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.
Full Text Available Abstract Background The lack of a uniform way for qualitative and quantitative evaluation of vaccine candidates under development led us to set up a standardized scheme for vaccine efficacy and safety evaluation. We developed and implemented molecular and immunology methods, and designed support tools for immunization data storage and analyses. Such collection can create a unique opportunity for immunologists to analyse data delivered from their laboratories. Results We designed and implemented GeVaDSs (Genetic Vaccine Decision Support system an interactive system for efficient storage, integration, retrieval and representation of data. Moreover, GeVaDSs allows for relevant association and interpretation of data, and thus for knowledge-based generation of testable hypotheses of vaccine responses. Conclusions GeVaDSs has been tested by several laboratories in Europe, and proved its usefulness in vaccine analysis. Case study of its application is presented in the additional files. The system is available at: http://gevads.cs.put.poznan.pl/preview/(login: viewer, password: password.
Ono, Akihiko; Azukizawa, Hiroaki; Ito, Sayami; Nakamura, Yuki; Asada, Hideo; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Hirobe, Sachiko; Okada, Naoki
Microneedle (MN) patches have great potential as transcutaneous vaccine delivery devices because MNs can effectively deliver vaccine antigen into the skin through the micropores formed in the stratum corneum by low-invasive and painless skin puncturing. This study aims to develop novel double-decker MN patches which have not only high safety and efficacy but also broad applicability to various vaccine antigens. We developed two types of MN patches (PGA-MN and Nylon-MN) that are made from polyglycolic acid and Nylon-6. In pre-clinical studies, both MN patches could demonstrably deliver antigens into resected human dermal tissue, prolong antigen deposition and increase antigen-specific IgG levels after vaccination compared with conventional injections. We demonstrated both MN patches could be safely applied to human skin because no broken MNs or significant skin irritation were observed after applications in the clinical research. PGA-MN was suggested to be superior to Nylon-MN regarding human skin puncturability based on measurements of transepidermal water loss and needle failure force. A high content of tetravalent influenza hemagglutinin antigens loaded on PGA-MN could stably maintain HA titers at 35°C for 1year. Overall, double-decker MN patches can reliably and safely puncture human skin and are promising as effective transcutaneous vaccine delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.
Ahmed, Yousuf; Tian, Meijuan; Gao, Yong
The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.
This study evaluated the ability of inactivated oil-emulsion ND Komarov vaccine to ... serotype 1 group, classified in the genus. Avulavirus ... Scientific Research Ethics, University of. Nigeria ... Research and Teaching and Quarantine. Service.
any negative effects on total proteins and calcium concentration in vaccinated infected when compared to the unvaccinated ..... I. H. (2010): Infection dynamics of .... molecular investigation of Newcastle disease in household chicken flocks and.
Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil
Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQβ-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs.
Full Text Available Despite decades of intensive research efforts there is currently no vaccine that provides sustained sterile immunity against malaria. In this context, a large number of targets from the different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates. None of these candidates has fulfilled expectations, and as long as we lack a single target that induces strain-transcending protective immune responses, combining key antigens from different life cycle stages seems to be the most promising route towards the development of efficacious malaria vaccines. After the identification of potential targets using approaches such as omics-based technology and reverse immunology, the rapid expression, purification and characterization of these proteins, as well as the generation and analysis of fusion constructs combining different promising antigens or antigen domains before committing to expensive and time consuming clinical development, represents one of the bottlenecks in the vaccine development pipeline. The production of recombinant proteins by transient gene expression in plants is a robust and versatile alternative to cell-based microbial and eukaryotic production platforms. The transfection of plant tissues and/or whole plants using Agrobacterium tumefaciens offers a low technical entry barrier, low costs and a high degree of flexibility embedded within a rapid and scalable workflow. Recombinant proteins can easily be targeted to different subcellular compartments according to their physicochemical requirements, including post-translational modifications, to ensure optimal yields of high quality product, and to support simple and economical downstream processing. Here we demonstrate the use of a plant transient expression platform based on transfection with A. tumefaciens as essential component of a malaria vaccine development workflow involving screens for expression, solubility and stability using fluorescent fusion
Nanni, Loris; Brahnam, Sheryl; Lumini, Alessandra
The aim of this work is to analyze and compare several feature extraction methods for peptide classification that are based on the calculation of texture descriptors starting from a matrix representation of the peptide. This texture-based representation of the peptide is then used to train a support vector machine classifier. In our experiments, the best results are obtained using local binary patterns variants and the discrete cosine transform with selected coefficients. These results are better than those previously reported that employed texture descriptors for peptide representation. In addition, we perform experiments that combine standard approaches based on amino acid sequence. The experimental section reports several tests performed on a vaccine dataset for the prediction of peptides that bind human leukocyte antigens and on a human immunodeficiency virus (HIV-1). Experimental results confirm the usefulness of our novel descriptors. The matlab implementation of our approaches is available at http://bias.csr.unibo.it/nanni/TexturePeptide.zip.
Lund, Mogens; Jensen, Jørgen Dejgård
The aim of the article is to identify and analyse public-private incentives for the development and marketing of new animal vaccines within a real options methodological framework, and to investigate how real options methodology can be utilized to support economic incentives for vaccine development in a cost-effective way. The development of a vaccine against Campylobacter jejuni in poultry is applied as a case study. Employing the real options methodology, the net present value of the vaccine R&D project becomes larger than a purely probabilistic expected present value throughout the different stages of the project - and the net present value becomes larger, when more types of real options are taken into consideration. The insight from the real options analysis reveals opportunities for new policies to promote the development of animal vaccines. One such approach might be to develop schemes combining stage-by-stage optimized subsidies in the individual development stages, with proper account taken of investors'/developers' economic incentives to proceed, sell or cancel the project in the respective stages. Another way of using the real options approach to support the development of desirable animal vaccines could be to issue put options for the vaccine candidate, enabling vaccine developers to hedge against the economic risk from market volatility. Copyright © 2016 Elsevier B.V. All rights reserved.
Loy John Dustin
Full Text Available Abstract Background Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen. Findings Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were generated and expression was confirmed in vitro using polyclonal and monoclonal antibodies specific to E2. Vaccine made from particles was generated in Vero cells and administered to BVDV free calves in a prime/boost regimen at two dosage levels. Vaccination resulted in neutralizing antibody titers that cross-neutralized both type 1 and type 2 BVD genotypes following booster vaccination. Additionally, high dose vaccine administration demonstrated some protection from clinical disease and significantly reduced the degree of leukopenia caused by viral infection. Conclusions Replicon particle vaccines administered in a prime/boost regimen expressing BVDV E2 glycoprotein can induce cross-neutralizing titers, reduce leukopenia post challenge, and mitigate clinical disease in calves. This strategy holds promise for a safe and effective vaccine to BVDV.
Myrna C Bonaldo
Full Text Available The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF, dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.
Development of shampoo, soap and ointment formulated by green synthesised silver nanoparticles functionalised with antimicrobial plants oils in veterinary dermatology: treatment and prevention strategies.
Bansod, Sunita Dashrath; Bawaskar, Manisha Subrashrao; Gade, Aniket Krishnarao; Rai, Mahendra Kumar
Many scientists have focused their research on the role of nanotechnology for the control of human pathogens, but there are also many topical pathogens present in animals, which infect animals and transfer to humans. Topical therapy is extremely important for the management of dermatological condition in animals. Therefore, the present study aims to evaluate the efficacy of biogenic silver nanoparticles (AgNPs) in combination with herbal oils against animal skin infections which may be responsible for causing infections in human beings. Here, the authors synthesised and characterised the AgNPs from Azadirachta indica. The oils were extracted from medicinal plants including Cymbopogon citratus, Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the antifungal and antibacterial activity of plant oils along with AgNPs were evaluated. An excision wound model was used for the study of wound healing activity in rabbits. AgNPs functionalised oil has demonstrated remarkable antimicrobial activity against pathogens present on the skin of animals. The nano-functionalised antimicrobial oils were used in the formulation of shampoo, soap and ointment for veterinary dermatology. Antimicrobial products of plant origin with AgNPs are valuable, safe and have a specific role in controlling diseases. The authors believe that this approach will be a good alternative therapy to solve the continuous antibiotic resistance developed by many bacterial pathogens and will be utilised in various animal contacting areas in medicine.
Bengtsson, Camilla; Kapetanovic, Meliha C; Källberg, Henrik; Sverdrup, Berit; Nordmark, Birgitta; Klareskog, Lars; Alfredsson, Lars
To investigate the association between vaccinations in adults and the risk of developing rheumatoid arthritis (RA). Data from the Swedish population-based Epidemiological Investigation of RA case-control study encompassing 1998 incident cases of RA aged 18-70 years and 2252 randomly selected controls matched for age, sex and residency were analysed. Those vaccinated within 5 years before disease onset were compared with those not vaccinated by calculating OR with 95% CI. Vaccinations neither increased the risk of RA overall (OR 1.0, 95% CI 0.9 to 1.1) nor the risk of two major subgroups of RA (antibodies to citrullinated peptide-positive (ACPA-positive) and ACPA-negative disease). Furthermore, vaccinations did not increase the risk of RA in smokers or carriers of HLA-DRB1 shared epitope alleles, two groups with established risk factors for RA. In this case-control study of incident cases of newly diagnosed RA, no increased risk of RA following immunisation was observed for vaccinations overall or for any specific vaccination. This indicates that immunological provocation of adults with commonly used vaccines in their present form carries no risk of RA. These findings should be implemented among public healthcare providers in order to encourage vaccinations according to recommended national vaccination schedules.
Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.