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Topic:Vaccine development

Vaccine development in horses involves the creation and refinement of immunizations to protect equine populations from infectious diseases. This process includes identifying antigens, formulating vaccines, and evaluating their safety and efficacy through clinical trials. Vaccines stimulate the horse's immune system to recognize and combat specific pathogens, thereby reducing the incidence and severity of diseases. Common equine vaccines target diseases such as equine influenza, tetanus, and West Nile virus. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, challenges, and advancements in vaccine development for equine health.
The evolving means of protecting horses against West Nile infection through immunisation.
Equine veterinary journal    December 11, 2007   Volume 39, Issue 6 484-485 doi: 10.2746/042516407X247116
Traub-Dargatz JL, Cordes T, Evans MB.No abstract available
Safety of an attenuated West Nile virus vaccine, live Flavivirus chimera in horses.
Equine veterinary journal    December 11, 2007   Volume 39, Issue 6 486-490 doi: 10.2746/042516407X214473
Long MT, Gibbs EP, Mellencamp MW, Zhang S, Barnett DC, Seino KK, Beachboard SE, Humphrey PP.West Nile virus (WNV) infection is endemic and able to cause disease in naive hosts. It is necessary therefore to evaluate the safety of new vaccines. Objective: To establish: 1) the safety of a modified live Flavivirus/West Nile virus (WN-FV) chimera by administration of an overdose and testing for shed of vaccine virus and spread to uninoculated sentinel horses; 2) that this vaccine did not become pathogenic once passaged in horses; and 3) vaccine safety under field conditions. Methods: There were 3 protocols: 1) In the overdose/shed and spread study, horses were vaccinated with a 100x immun...
Efficacy, duration, and onset of immunogenicity of a West Nile virus vaccine, live Flavivirus chimera, in horses with a clinical disease challenge model.
Equine veterinary journal    December 11, 2007   Volume 39, Issue 6 491-497 doi: 10.2746/042516407X217416
Long MT, Gibbs EP, Mellencamp MW, Bowen RA, Seino KK, Zhang S, Beachboard SE, Humphrey PP.West Nile virus (WNF) is a Flavivirus responsible for a life-threatening neurological disease in man and horses. Development of improved vaccines against Flavivirus infections is therefore important. Objective: To establish that a single immunogenicity dose of live Flavivirus chimera (WN-FV) vaccine protects horses from the disease and it induces a protective immune response, and to determine the duration of the protective immunity. Methods: Clinical signs were compared between vaccinated (VACC) and control (CTRL) horses after an intrathecal WNV challenge given at 10 or 28 days, or 12 months p...
Alternative vaccination against equine botulism (BoNT/C).
Equine veterinary journal    December 11, 2007   Volume 39, Issue 6 516-520 doi: 10.2746/042516407X236550
Frey J, Eberle S, Stahl C, Mazuet C, Popoff M, Schatzmann E, Gerber V, Dungu B, Straub R.In Europe the incidence of botulism in horses has increased in the last decade due to the growing popularity of haylage feeding. Recombinant vaccines are safer and less expensive to produce and are generally better tolerated than toxoids. Objective: To investigate whether the recombinant C-terminal half of the heavy chain of the botulinum neurotoxin C (Hc BoNT/C) in combination with an immunstimulatory adjuvant is an appropriate vaccine candidate for horses by testing its efficacy to induce neutralising antibodies and by comparing its immunogenic properties and adverse reactions to a commercia...
Glanders: off to the races with Burkholderia mallei.
FEMS microbiology letters    November 23, 2007   Volume 277, Issue 2 115-122 doi: 10.1111/j.1574-6968.2007.00949.x
Whitlock GC, Estes DM, Torres AG.Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with infected animals. The use of B. mallei as a biological weapon has been reported and currently, there is no vaccine available for either humans or animals. Despite the history and highly infective nature of B. mallei, as well as its potential use as a bio-weapon, B. mallei research to understand the pathogenesis and the host responses to infection remains limited. Therefore, this minireview will focus on current efforts to elucida...
Safety and immunogenicity of a live-attenuated auxotrophic candidate vaccine against the intracellular pathogen Rhodococcus equi.
Vaccine    November 21, 2007   Volume 26, Issue 7 998-1009 doi: 10.1016/j.vaccine.2007.10.069
Lopez AM, Townsend HG, Allen AL, Hondalus MK.Rhodococcus equi causes serious pneumonia in neonatal foals and is an opportunistic pathogen of people with compromised cellular immunity. No effective vaccine against R. equi disease in foals is available. We tested the safety and immunogenicity of a live, fully attenuated riboflavin auxotrophic candidate vaccine strain of R. equi (R. equi rib-). We demonstrated that R. equi rib- is immunogenic and capable of inducing IFN-gamma responses in immunocompetent BALB/c mice, yet it is safe even in an immunocompromised SCID mouse infection model. Moreover, it protects immunocompetent mice against vi...
Genetic relatedness of recent Canadian equine influenza virus isolates with vaccine strains used in the field.
The Canadian veterinary journal = La revue veterinaire canadienne    November 9, 2007   Volume 48, Issue 10 1028-1030 
Gagnon CA, Elahi SM, Tremblay D, Lavoie JP, Bryant NA, Elton DM, Carman S, Elsener J.No abstract available
Monoclonal antibodies against the nucleocapsid proteins of henipaviruses: production, epitope mapping and application in immunohistochemistry.
Archives of virology    November 5, 2007   Volume 153, Issue 2 273-281 doi: 10.1007/s00705-007-1079-x
Xiao C, Liu Y, Jiang Y, Magoffin DE, Guo H, Xuan H, Wang G, Wang LF, Tu C.Four monoclonal antibodies (mAbs) were generated by immunizing BALB/C mice with recombinant nucleocapsid protein (N) of Nipah virus (NiV) and Hendra virus (HeV) expressed in E. coli. Two mAbs each were obtained for the HeV N and NiV N, respectively. All four mAbs displayed specific reactivity with the recombinant N proteins of both viruses by western blot, which was further confirmed by immunofluorescent antibody assay using fixed insect cells infected with recombinant baculoviruses expressing either the HeV or NiV N protein. Epitope mapping using a 12-mer random peptide phage display library ...
Seroprevalence and risk factors for infection with West Nile virus in Saskatchewan horses, 2003.
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire    October 25, 2007   Volume 71, Issue 4 256-263 
Epp T, Waldner C, Leighton FA, Berke O, Townsend HG.The primary objectives of this study were to determine the seroprevalence of West Nile virus (WNV) infection of horses in Saskatchewan in 2003 and to identify risk factors for the infection. Blood samples were collected in August and October from 212 horses in 20 herds in 5 geographic zones. After accounting for within-herd clustering, the proportion of horses that had been infected with WNV, as determined by IgG and IgM antibody response, was 55.7% (95% confidence interval, 44.9% to 65.8%). The proportion of antibody-positive horses differed among herds (0% to 100%) and across ecoregions (20%...
Safety and efficacy in geese of a PER.C6-based inactivated West Nile virus vaccine.
Vaccine    October 15, 2007   Volume 25, Issue 49 8338-8345 doi: 10.1016/j.vaccine.2007.09.055
Samina I, Havenga M, Koudstaal W, Khinich Y, Koldijk M, Malkinson M, Simanov M, Perl S, Gijsbers L, Weverling GJ, Uytdehaag F, Goudsmit J.Studies were performed with an inactivated vaccine against the mosquito-borne flavivirus, West Nile virus (WNV). The mammalian cell line, PER.C6, was selected as the platform for WNV growth since both the neurovirulent strains NY99 and ISR98 that cause epidemics in humans and high mortality in geese, respectively, could be propagated to high titers (10(9) to 10(10)TCID(50)/ml) on these cells. Based on the high DNA homology of the WNV envelope (E) protein and non-structural protein 5 (NS5), and identical neurovirulence in mice and geese, we concluded that NY99 and ISR98 viruses are closely rela...
Preliminary study of mucosal IgA in the equine small intestine: specific IgA in cases of acute grass sickness and controls.
Equine veterinary journal    October 4, 2007   Volume 39, Issue 5 457-460 doi: 10.2746/042516407x193189
Nunn FG, Pirie RS, McGorum B, Wernery U, Poxton IR.There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. Objective: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract...
Rhodococcus equi infection in foals: the science of ‘rattles’.
Equine veterinary journal    October 4, 2007   Volume 39, Issue 5 470-478 doi: 10.2746/042516407x209217
Muscatello G, Leadon DP, Klayt M, Ocampo-Sosa A, Lewis DA, Fogarty U, Buckley T, Gilkerson JR, Meijer WG, Vazquez-Boland JA.Infection with Rhodococcus (Corynebacterium) equi is a well-recognised condition in foals that represents a consistent and serious risk worldwide. The condition manifests itself primarily as one of pulmonary abscessation and bronchitis, hence the terminology of 'rattles' derived from its most obvious clinical sign, frequently terminal when first identified. This review addresses the clinical manifestation, bacteriology and pathogenesis of the condition together with recent developments providing knowledge of the organism in terms of virulence, epidemiology, transmission and immune responses. E...
Equine influenza vaccine containing older H3N8 strains offers protection against A/eq/South Africa/4/03 (H3N8) strain in a short-term vaccine efficacy study.
Equine veterinary journal    October 4, 2007   Volume 39, Issue 5 446-450 doi: 10.2746/042516407x180327
Daly JM, Sindle T, Tearle J, Barquero N, Newton JR, Corning S.Surveillance of equine influenza viruses has suggested that strains included in currently licensed vaccines are a poor match for those predominantly circulating in the field. Objective: To assess the ability of Duvaxyn IE-T Plus to provide cross protection against the newly evolved South Africa/4/03 (H3N8) strain of equine influenza virus. Methods: The vaccine efficacy was evaluated by challenge infection with influenza strain A/eq/South Africa/4/03 (H3N8) 2 weeks after a primary course of 2 vaccinations with Duvaxyn IE-T Plus given at a 4-week interval. The outcome of challenge in vaccinated ...
Evaluation of the safety, immunogenicity and pharmacokinetics of equine anti-SARS-CoV F(ab’)(2) in macaque.
International immunopharmacology    October 4, 2007   Volume 7, Issue 13 1834-1840 doi: 10.1016/j.intimp.2007.09.011
Xu Y, Jia Z, Zhou L, Wang L, Li J, Liang Y, Zhao T, Ni B, Wu Y.To warrant potential clinical testing, the equine anti-SARS-CoV F(ab')(2) requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab')(2) fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS-CoV F(ab')(2) or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this an...
Analysis of Venezuelan equine encephalitis virus capsid protein function in the inhibition of cellular transcription.
Journal of virology    October 3, 2007   Volume 81, Issue 24 13552-13565 doi: 10.1128/JVI.01576-07
Garmashova N, Atasheva S, Kang W, Weaver SC, Frolova E, Frolov I.The encephalitogenic New World alphaviruses, including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses, constitute a continuing public health threat in the United States. They circulate in Central, South, and North America and have the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that these viruses have developed the ability to interfere with cellular transcription and use it as a means of downregulating a cellular antiviral response. The results of the present study suggest that the N-terminal, approxima...
Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine.
Journal of virology    October 3, 2007   Volume 81, Issue 24 13412-13423 doi: 10.1128/JVI.01799-07
Ljungberg K, Whitmore AC, Fluet ME, Moran TP, Shabman RS, Collier ML, Kraus AA, Thompson JM, Montefiori DC, Beard C, Johnston RE.A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly ...
Genetic characterization of equine influenza viruses isolated in Italy between 1999 and 2005.
Virus research    September 24, 2007   Volume 131, Issue 1 100-105 doi: 10.1016/j.virusres.2007.08.001
Damiani AM, Scicluna MT, Ciabatti I, Cardeti G, Sala M, Vulcano G, Cordioli P, Martella V, Amaddeo D, Autorino GL.During local respiratory disease outbreaks, occurring in 2003 and 2004 in horse training stables within race-tracks in Rome, and on a stud horse farm in Bari in 2005, four strains of equine influenza (EI) virus were isolated. All outbreaks occurred in flu-vaccinated horses. Here, we are reporting the results of the genetic characterization of these isolates, together with that of another EI virus strain isolated in 1999 from a dead foal presenting pulmonary lesions. Alignment and phylogenetic analyses were carried out using the haemagglutinin amino acid sequences. The Rome and Bari isolates we...
New assays to measure equine influenza virus-specific Type 1 immunity in horses.
Vaccine    September 4, 2007   Volume 25, Issue 42 7385-7398 doi: 10.1016/j.vaccine.2007.08.033
Paillot R, Kydd JH, MacRae S, Minke JM, Hannant D, Daly JM.Equine influenza virus (EIV) is a leading cause of respiratory disease in horses. Equine influenza infection induces a long-term immunity to re-infection. Recent strategies of vaccination aim to mimic this immunity by stimulating both antibody and cellular immune responses. Cell-mediated immunity (CMI) to influenza is well defined in man, but little has been done to characterise the responses in the horse. Additionally, the development of reliable assays for the measurement of equine CMI has lagged behind serological methods and vaccine development. In this study, two methods of measuring EIV-...
Boosting in equine influenza vaccination schedules: timing and time for a re-evaluation of requirements of national and international authorities.
Veterinary journal (London, England : 1997)    August 16, 2007   Volume 174, Issue 3 449-450 doi: 10.1016/j.tvjl.2007.06.012
Wood JL, Mumford JA, Mair TS, Slater J.No abstract available
Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.
Vaccine    August 15, 2007   Volume 25, Issue 43 7582-7597 doi: 10.1016/j.vaccine.2007.07.055
Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA.Improving the ability of DNA-based vaccines to induce potent Type1/Th1 responses against intracellular pathogens in large outbred species is essential. Rhodoccocus equi and equine infectious anemia virus (EIAV) are two naturally occurring equine pathogens that also serve as important large animal models of neonatal immunity and lentiviral immune control. Neonates present a unique challenge for immunization due to their diminished immunologic capabilities and apparent Th2 bias. In an effort to augment R. equi- and EIAV-specific Th1 responses induced by DNA vaccination, we hypothesized that a du...
Comparative efficacies of three commercially available vaccines against West Nile Virus (WNV) in a short-duration challenge trial involving an equine WNV encephalitis model.
Clinical and vaccine immunology : CVI    August 8, 2007   Volume 14, Issue 11 1465-1471 doi: 10.1128/CVI.00249-07
Seino KK, Long MT, Gibbs EP, Bowen RA, Beachboard SE, Humphrey PP, Dixon MA, Bourgeois MA.We used a severe challenge model that produces clinical West Nile virus (WNV) disease to test the efficacy of three commercially available equine WNV vaccines in horses. Twenty-four healthy, WNV-seronegative horses of varying ages and genders were placed, in random and blind manner, into three trial groups consisting of eight horses each; two horses in each group received (i) an inactivated WNV vaccine (K-WN), (ii) a modified-live vaccine (CP-WN) containing the WNV prM and E proteins expressed by a canarypox vector, (iii) a live-chimera vaccine (WN-FV) containing WNV prM and E proteins express...
The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.
Molecular immunology    July 31, 2007   Volume 45, Issue 3 818-827 doi: 10.1016/j.molimm.2007.06.158
Lewis MJ, Wagner B, Woof JM.Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately t...
Immunocontraception and increased longevity in equids.
Zoo biology    July 1, 2007   Volume 26, Issue 4 237-244 doi: 10.1002/zoo.20109
Kirkpatrick JF, Turner A.Intensive population management by means of fertility control has been shown to change the age profile of a wild horse herd. The primary change has been an increase in the number and percent of older animals, as expected, but also the appearance of new and older age classes. An examination of direct effects of fertility control on two groups of treated animals shows a significant increase in longevity over non-treated animals that is associated with contraceptive treatment. The mean age at death (MAD) was calculated for 128 wild horses for which precise birth and death dates were known, includ...
Effective priming of foals born to immune dams against influenza by a canarypox-vectored recombinant influenza H3N8 vaccine.
Journal of comparative pathology    June 7, 2007   Volume 137 Suppl 1 S76-S80 doi: 10.1016/j.jcpa.2007.04.016
Minke JM, Toulemonde CE, Dinic S, Cozette V, Cullinane A, Audonnet JC.A classical limitation of early life immunization is the interference by maternally derived antibodies, which are known to inhibit the immune response to modified-live and killed vaccines. Several studies have convincingly shown that even minute amounts of maternally derived antibodies against equine influenza can strongly interfere with successful vaccination of foals born to immune mares. In this study we evaluated the response of foals born to vaccinated mares to immunization with a canarypox-vectored recombinant vaccine against equine influenza virus H3N8. The recombinant vaccine was able ...
Strangles vaccines in trouble again.
Equine veterinary journal    May 25, 2007   Volume 39, Issue 3 196 doi: 10.2746/042516407x196744
Timoney JF.No abstract available
Immunization by intrabronchial administration to 1-week-old foals of an unmarked double gene disruption strain of Rhodococcus equi strain 103+.
Veterinary microbiology    May 18, 2007   Volume 125, Issue 1-2 100-110 doi: 10.1016/j.vetmic.2007.05.007
Pei Y, Nicholson V, Woods K, Prescott JF.Rhodococcus equi causes fatal granulomatous pneumonia in foals and immunocompromised animals and humans. However, there is no effective vaccine against this infection. In this study, the chromosomal genes isocitrate lyase (icl) and cholesterol oxidase (choE) were chosen as targets for mutation and assessment of the double mutant as an intrabronchial vaccine in 1-week-old foals. Using a modification of a suicide plasmid previously developed in this laboratory, we developed a choE-icl unmarked deletion mutant of R. equi strain 103+. Five 1-week-old foals were infected intrabronchially with the m...
Experimental infections with West Nile virus.
Current opinion in infectious diseases    May 2, 2007   Volume 20, Issue 3 293-297 doi: 10.1097/QCO.0b013e32816b5cad
Bowen RA, Nemeth NM.West Nile virus emerged recently in North America as a serious human and animal pathogen. This review summarizes the use of experimental infections with West Nile virus in diverse vertebrate species that have been used to answer fundamental questions about the host response, pathogenesis of West Nile virus infection and virus evolution. Results: West Nile virus has an extremely broad vertebrate host range. Infection of common species of birds has defined those with high vs. low potential to serve as amplifying hosts for the virus. In general, mammals (primates, horses, companion animals) are d...
Restricted and selective tropism of a Venezuelan equine encephalitis virus-derived replicon vector for human dendritic cells.
Viral immunology    April 12, 2007   Volume 20, Issue 1 88-104 doi: 10.1089/vim.2006.0090
Nishimoto KP, Laust AK, Wang K, Kamrud KI, Hubby B, Smith JF, Nelson EL.Dendritic cells (DCs) consist of heterogeneous phenotypic populations and have diverse immunostimulatory functions dependent on both lineage and functional phenotype, but as exceptionally potent antigen-presenting cells, they are targets for generating effective antigen-specific immune responses. A promising replicon particle vector derived from Venezuelan equine encephalitis virus (VEE) has been reported to transduce murine footpad DCs. However, the receptive DC subset, the degree of restriction for this tropism, and the extent of conservation between rodents and humans have not been well cha...
Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus.
The Journal of general virology    March 22, 2007   Volume 88, Issue Pt 4 1324-1336 doi: 10.1099/vir.0.82391-0
Tagmyer TL, Craigo JK, Cook SJ, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whi...
Burkholderia Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis.
BMC microbiology    March 15, 2007   Volume 7 19 doi: 10.1186/1471-2180-7-19
Tiyawisutsri R, Holden MT, Tumapa S, Rengpipat S, Clarke SR, Foster SJ, Nierman WC, Day NP, Peacock SJ.The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. Results: Using bacteriophage-mediated immunoscreening we identified genes expressed in vivo during experimental equine glanders infection. A family of immunodominant antigens were identified that share protein domain architectures with hemagglutinins and invasins. These have been designated Burkholderia Hep_Hag autotransporter (BuHA)...
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