Development Of Veterinary Vaccines Research Articles

Use of Veterinary Vaccines for Livestock as a Strategy to Control Foodborne Parasitic Diseases.

Foodborne diseases (FBDs) are a major concern worldwide since they are associated with high mortality and morbidity in the human population. Among the causative agents of FBDs, Taenia solium, Echinococcus granulosus, Toxoplasma gondii, Cryptosporidium spp., and Trichinella spiralis are listed in the top global risk ranking of foodborne parasites. One common feature between them is that they affect domestic livestock, encompassing an enormous risk to global food production and human health from farm to fork, infecting animals, and people either directly or indirectly. Several approaches have been employed to control FBDs caused by parasites, including veterinary vaccines for livestock. Veterinary vaccines against foodborne parasites not only improve the animal health by controlling animal infections but also contribute to increase public health by controlling an important source of FBDs. In the present review, we discuss the advances in the development of veterinary vaccines for domestic livestock as a strategy to control foodborne parasitic diseases.

A Veterinary Vaccine Development Process Map to assist in the development of new vaccines

The UK Government recognised the importance of vaccines in the control of new emerging disease threats and in 2015 established the UK Vaccine Network to focus on specific areas of need. One of these was the understanding of what is involved in the development of a new vaccine and what are the potential bottlenecks to a rapid response in the face of an epidemic such as Ebola, MERS and more recently COVID-19. A Working Group was established to initially produce a Vaccine Development Process Map for a Human Vaccine. However, in view of the importance of animal wellbeing and the significant impact of diseases with Zoonotic potential, a similar Map has been created outlining the Veterinary Vaccine Development Process. This paper describes the production of that Map and covers the process from the generation of a Target Product Profile (TPP) through Discovery and Feasibility, and on to Product Development and Registration.

West Nile Virus: Veterinary Health and Vaccine Development.

West Nile virus (WNV) (Flaviviridae: Flavivirus) was discovered in Africa more than 80 yr ago and became recognized as an avian pathogen and a cause of neurologic disease in horses largely during periodic incursions into Europe. Introduction of WNV into North America stimulated great anxiety, particularly in the equine industry, but also for pet owners and livestock producers concerned about the effect of WNV on other domestic animals. Numerous subsequent studies of naturally occurring and experimentally induced disease greatly expanded our understanding of the host range and clinical consequences of WNV infection in diverse species and led to rapid development and deployment of efficacious vaccines for horses. In addition to humans, horses are clearly the animals most frequently affected by serious, sometimes lethal disease following infection with WNV, but are dead-end hosts due to the low-magnitude viremia they develop. Dogs, cats, and livestock species including chickens are readily infected with WNV, but only occasionally develop clinical disease and are considered dead-end hosts for the virus.

A Novel Cre Recombinase-Mediated In Vivo Minicircle DNA (CRIM) Vaccine Provides Partial Protection against Newcastle Disease Virus.

Minicircle DNA (mcDNA), which contains only the necessary components for eukaryotic expression and is thus smaller than traditional plasmids, has been designed for application in genetic manipulation. In this study, we constructed a novel plasmid containing both the Cre recombinase under the phosphoglycerate kinase (PGK) promoter and recombinant lox66 and lox71 sites located outside the cytomegalovirus (CMV) expression cassette. The strictly controlled synthesis of Cre recombinase in vivo maintained the complete form of the plasmid in vitro, whereas the in vivo production of Cre transformed the parental plasmid to mcDNA after transfection. The newly designed Cre recombinase-mediated in vivomcDNA platform, named CRIM, significantly increased the nuclear entry of mcDNA, followed by increased production of mRNA and protein, using enhanced green fluorescent protein (EGFP) as a model. Similar results were also observed in chickens when the vaccine was delivered by the regulated-delayed-lysis Salmonella strain χ11218, where significantly increased production of EGFP was observed in chicken livers. Then, we used the HN gene of genotype VII Newcastle disease virus as an antigen model to construct the traditional plasmid pYL43 and the novel mcDNA plasmid pYL47. After immunization, our CRIM vaccine provided significantly increased protection against challenge compared with that of the traditional plasmid, providing us with a novel mcDNA vaccine platform.IMPORTANCE Minicircle DNA (mcDNA) has been considered an attractive alternative to DNA vaccines; however, the relatively high cost and complicated process of purifying mcDNA dramatically restricts the application of mcDNA in the veterinary field. We designed a novel in vivo mcDNA platform in which the complete plasmid could spontaneously transform into mcDNA in vivo In combination with the regulated-delayed-lysis Salmonella strain, the newly designed mcDNA vaccine provides us with an elegant platform for veterinary vaccine development.

Vaccines against Trichinellaspiralis: Progress, challenges and future prospects.

Trichinellaspiralis, the causative agent of trichinellosis, is able to infect a wide range of carnivores and omnivores including human beings. In the past 30years, a mass of vaccination efforts has been performed to control T.spiralis infection with the purpose of reduction in worm fecundity or decrease in muscle larval and adult burdens. Here, we summarize the development of veterinary vaccines against T.spiralis infection. During recent years, increasing numbers of new vaccine candidates have been developed on the protective immunity against T.spiralis infection in murine model. The vaccine candidates were not only selected from excretory-secretory (ES) antigens, but also from the recombinant functional proteins, such as proteases and some other antigens participated in T.spiralis intracellular processes. However, immunization with a single antigen generally revealed lower protective effects against T.spiralis infection in mice compared to that with the inactivated whole worms or crude extraction and ES productions. Future study of T.spiralis vaccines should focus on evaluation of the protective efficacy of antigens and/or ligands delivered by nanoparticles that could elicit Th2-type immune response on experimental pigs.

Update on Veterinary Viral Vaccines: A Review

Vaccine has made a very significant impact on the control of viral diseases in both humans and animal species. Worldwide eradication of small pox and rinderpest an d drastic reduction in other infection disease are confirming to the fact that vaccination is the most feasible and cost effective strategy for prevention, control and eradication of infectious disease. Veterinary science has made a significant contributio n to the field of vaccine research and development. Among the numerous of infectious diseases in animals, those of viral etiology account for a high burden of cases and they are the most relevant from a veterinary perspective. So, vaccination is the most f easible means that has to be implemented for controlling and eradicating these diseases. The viral vaccines used in veterinary medicine generally categorized into 1 of 3 categories: inactivated vaccines (in which antigens are typically combined with adjuva nts); live attenuated vaccines; and recombinant technology vaccines, which may include subunit antigens or genetically engineered organisms. The majority of vaccines available today rely either on attenuation (weakening) techniques or inactivated (killed) forms of the infectious agent. Even though many vaccines are available and vaccine producing technologies are existed, several viral disease s have no vaccines yet and there are also limitations even on existing vaccines. Therefore, the objective of this seminar paper is to overview the development of veterinary viral vaccines and challenges and opportunities existing in the process of its deve lopment. To be profitable from the veterinary viral vaccines the challenging factors for the development of the vaccines should be managed. In addition, the novel vaccine technologies should be encouraged because they can fill the limitations of convention al live and killed vaccines.

Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

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.

Evaluation of protective efficacy induced by different heterologous prime-boost strategies encoding triosephosphate isomerase against Schistosoma japonicum in mice

BackgroundIn China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice.MethodsDNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c miceResultsResults show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. priming-rAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model.ConclusionsA suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice.

Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

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.

Review on Adeno Virus; As a Vaccine Vehicle

Adenoviruses have moved to the forefront of vaccinology and are showing substantial prom ise as vehicles for antigen delivery for a number of vaccines currently being developed. Most studies to date have focused on human serotype adenoviruses, particularly human adenovirus type 5. Human serotype adenovirus vaccine vectors are particularly usef ul for development of veterinary vaccines as neutralizing antibodies to the vector will not usually be present in the vaccinates. Most vectors currently used as vaccine carriers are deleted in E1 gene. The original E1 deleted adenoviral vectors were constr ucted by homologous recombination. Replication incompetent vectors contain an antigen expression cassette substituted for the deleted E1A – E1B region. These replication incompitant adenoviruses can not replicate because of the deletion of the essential vir al E1 gene region containing two genes. Replication competent adenoviral vectors encode all of the remaining adenoviral antigens in addition to the transgene product, i.e., the vaccine antigen. The potential for adenoviruses to elicit powerful B cell and T cell responses in the mammalian host are the main reason for the use of these vectors in vaccine development. For effective veterinary use, extensive research on adenoviral vaccine vectors should be undertaken.

Toward Developing a Preventive MERS-CoV Vaccine-Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14-15, 2015.

Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14–15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed.

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

Oral vaccination of fish: Lessons from humans and veterinary species

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.

Challenges in Veterinary Vaccine Development and Immunization.

In approaching the development of a veterinary vaccine, researchers must choose from a bewildering array of options that can be combined to enhance benefit. The choice and combination of options is not just driven by efficacy, but also consideration of the cost, practicality, and challenges faced in licensing the product. In this review we set out the different choices faced by veterinary vaccine developers, highlight some issues, and propose some pressing needs to be addressed.

Rapeseed oil and ginseng saponins work synergistically to enhance Th1 and Th2 immune responses induced by the foot-and-mouth disease vaccine.

Previous investigations demonstrated that saponins isolated from the root of Panax ginseng C. A. Meyer (i.e., ginseng root saponin [GS-R]) had adjuvant activity. In the present study, the combined effects of rapeseed oil (RO) and GS-R on the immune responses elicited by foot-and-mouth disease (FMD) vaccine were investigated by measuring FMD virus (FMDV)-specific antibody levels, cytokine levels, lymphocyte proliferation, and long-lived IgG-secreting plasma cells from bone marrow in a mouse model. The results indicated that RO in combination with GS-R significantly enhanced serum IgG and isotype concentrations, gamma interferon (IFN-γ) and interleukin 5 (IL-5) levels, splenocyte proliferative responses to stimulations with concanavalin A (ConA), lipopolysaccharide (LPS), and FMDV antigen, and the numbers of IgG-secreting plasma cells in the bone marrow, suggesting that RO/GS-R enhanced both Th1 and Th2 immune responses. In addition, no significant difference was found between RO/GS-R and the commercial adjuvant oil ISA 206 in the promotion of FMD vaccine-induced immune responses. Considering the vegetable origin of RO and GS-R and the potent adjuvant activity, RO/GS-R should be studied further for the development of veterinary vaccines, especially for use in food animals in order to promote food safety.

Construction and evaluation of replication-defective recombinant optimized triosephosphate isomerase adenoviral vaccination in Schistosoma japonicum challenged mice

Schistosomiasis is an endemic, zoonotic parasitic disease that remains a public health concern in China. Development of transmission blocking veterinary vaccines against Schistosoma japonicum infection is urgently needed. Replication-defective adenoviral vector is an efficient vaccine delivery system that has been widely used. Its use is associated with high levels of gene insertion and expression. It is easy to construct and prepare, and is safe. It is not known whether this delivery system can improve the protective effect of schistosome vaccination. Triosephosphate isomerase from S. japonicum (SjTPI) is a promising vaccine candidate. Thus far it has induced only partial protection in animal models and needs to be further enhanced to be effective. We constructed a replication-defective adenoviral vector-based vaccine with optimized SjTPI (rAdV-SjTPI.opt). The specific immune responses and protective efficiency in mice were evaluated. Results showed that intramuscular rAdV-SjTPI.opt induced Th1 biased immune responses in the host, while subcutaneous rAdV-SjTPI.opt induced Th2 predominant immune responses. Oral rAdV-SjTPI.opt induced low levels of immune responses and no significant protection. Intramuscular rAdV-SjTPI.opt provided a consistent and repeatable higher protective effect in mice (more than 50%). These findings may be due to the associated higher levels of specific Th1, antibody responses and partially lower level of IL-17A. This report provides a foundation for developing transmission-blocking veterinary vaccines in larger animals.

Possibilities and limitations in veterinary vaccine development using the example of classical swine fever

The use of vaccines is still one of the most effective tools to control infectious diseases. Up to now, conventional vaccines are employed in the majority of cases. Drawbacks of these established vaccines include the lack of differentiability of infected from vaccinated animals (DIVA or marker strategy), limitations in the efficacy spectrum, and constraints and restrictions in production. For this reason, new vaccines, which do not show these disadvantages, are under development, especially for notifiable diseases such as classical swine fever (CSF). In principle, the following modern vaccine types can be differentiated: recombinant attenuated vaccines, recombinant inactivated vaccines or subunit vaccines, vector vaccines, and DNA/ RNA vaccines. During the last years, especially attenuated deletion vaccines or chimeric constructs have shown potential. Under field conditions, all marker vaccines have to be accompanied by a potent test system. Particularly this point often shows weaknesses. Alternative vaccine candidates are so far only prototypes and licensing is only a medium term possibility. Moreover, most of these vaccines are genetically engineered and can be problematic in terms of licensing and the public's acceptance. In conclusion, conventional vaccines still present the standard, especially in terms of efficacy. Yet, only vaccines with DIVA properties are feasible for the control of CSF. Thus, development and assessment of alternative vaccines is of paramount importance. The present overview summarizes concepts and vaccine types using the example of classical swine fever. It also recapitulates their advantages and disadvantages as well as their limitations.

Equine influenza vaccines in Europe: A view from the animal health industry

Equine influenza vaccines in <scp>E</scp>urope: A view from the animal health industry

Adenoviral Vectors in Veterinary Vaccine Development: Potential for Further Development

Vaccines are an integral part of veterinary disease prevention. However there are still a significant number of veterinary diseases for which vaccines do not currently exist or where currently available vaccines do not provide adequate immunity. Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles because of their ability to elicit potent cell-mediated and humoral responses making them ideal for use against viruses and other intracellular pathogens. Adenoviral vector based vaccines are likely to play a significant role in overcoming these problems in the future. However, this vector is under utilized in veterinary vaccine development at this time. This review focuses on adenoviral vector based vaccines developed to date and explores the potential for veterinary vaccine development based upon this platform: advantages and potential disadvantages of this technology are discussed as well as the potential for developing efficacious commercial veterinary adenoviral vector based vaccines.

One-step spray-dried polyelectrolyte microparticles enhance the antigen cross-presentation capacity of porcine dendritic cells

Vaccination is regarded as the most efficient and cost-effective way to prevent infectious diseases. Vaccine design nowadays focuses on the implementation of safer recombinant subunit vaccines. However, these recombinant subunit antigens are often poor immunogens and several strategies are currently under investigation to enhance their immunogenicity. The encapsulation of antigens in biodegradable microparticulate delivery systems seems a promising strategy to boost their immunogenicity. Here, we evaluate the capacity of polyelectrolyte complex microparticles (PECMs), fabricated by single step spray-drying, to deliver antigens to porcine dendritic cells and how these particles affect the functional maturation of dendritic cells (DCs). As clinically relevant model antigen F4 fimbriae, a bacterial adhesin purified from a porcine-specific enterotoxigenic Escherichia coli strain was chosen. The resulting antigen-loaded PECMs are efficiently internalised by porcine monocyte-derived DCs. F4 fimbriae-loaded PECMs (F4-PECMs) enhanced CD40 and CD25 surface expression by DCs and this phenotypical maturation correlated with an increased secretion of IL-6 and IL-1β. More importantly, F4-PECMs enhance both the T cell stimulatory and antigen presentation capacity of DCs. Moreover, PECMs efficiently promoted the CD8+ T cell stimulatory capacity of dendritic cells, indicating an enhanced ability to cross-present the encapsulated antigens. These results could accelerate the development of veterinary and human subunit vaccines based on polyelectrolyte complex microparticles to induce protective immunity against a variety of extra- and intracellular pathogens.