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.
Lee DH, Lee EB, Seo JP, Ko EJ.Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objective: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination...
Kropich-Grant JN, Wiley KE, Manyweathers J, Thompson KR, Brookes VJ.Hendra virus disease (HeVD) is an emerging zoonosis in Australia, resulting from the transmission of Hendra virus (HeV) to horses from Pteropus bats. Vaccine uptake for horses is low despite the high case fatality rate of HeVD in both horses and people. We reviewed evidence-based communication interventions to promote and improve HeV vaccine uptake for horses by horse owners and conducted a preliminary evaluation of potential drivers for HeV vaccine uptake using the Behavioural and Social Drivers of Vaccination (BeSD) framework developed by the World Health Organization. Six records were eligi...
Jindra C, Hainisch EK, Brandt S.Horses and other equid species are frequently affected by bovine papillomavirus type 1 and/or 2 (BPV1, BPV2)-induced skin tumors termed sarcoids. Although sarcoids do not metastasize, they constitute a serious health problem due to their BPV1/2-mediated resistance to treatment and propensity to recrudesce in a more severe, multiple form following accidental or iatrogenic trauma. This review provides an overview on BPV1/2 infection and associated immune escape in the equid host and presents early and recent immunotherapeutic approaches in sarcoid management.
Yu YY, Xu MS, Liang H, Wang HY, Yu CQ, Liu Q.Despite over 40 years of research on the human immunodeficiency virus type 1 (HIV-1) vaccine, we still lack a considerable progress. Equine infectious anemia virus (EIAV) is a lentivirus in the Retroviridae family, akin to HIV-1 in genome structure and antigenicity. EIA is an important infectious disease in equids, characterized by anemia, persistent infection, and repeated fevers. The EIAV attenuated vaccine in China is the only lentiviral vaccine used on a large scale. Elucidating the mechanism of waning and induction of protective immunity from this attenuated vaccine strain will provide a ...
Carnet F, Perrin-Cocon L, Paillot R, Lotteau V, Pronost S, Vidalain PO.Vaccination is one of the most widely used strategies to protect horses against pathogens. However, available equine vaccines often have limitations, as they do not always provide effective, long-term protection and booster injections are often required. In addition, research efforts are needed to develop effective vaccines against emerging equine pathogens. In this review, we provide an inventory of approved adjuvants for equine vaccines worldwide, and discuss their composition and mode of action when available. A wide range of adjuvants are used in marketed vaccines for horses, the main fami...
Karamendin K, Abishov A, Kydyrmanov A, Akhmetzhanova M.In 2011, there was an outbreak of a disease with mass abortions among horses in southeastern Kazakhstan. The AK-2011 strain was isolated from an aborted fetus and subsequently identified as equid alphaherpesvirus 1. Here, we describe the nearly complete genome sequence of the AK-2011 strain, attenuated for vaccine development.
Luethy D.The continued recognition and emergence of alphavirus and flavivirus diseases is a growing veterinary and public health concern. As the global environment continues to change, mosquito-borne diseases will continue to evolve and expand. Continued development of readily available vaccines for the prevention of these diseases in humans and animals is essential to controlling epizootics of these diseases. Further research into effective antiviral treatments is also sorely needed. This article describes equine encephalitis viruses with a focus on clinical and public health considerations.
Hainisch EK, Jindra C, Kirnbauer R, Brandt S.Papillomaviruses (PVs) are a family of small DNA tumor viruses that can induce benign lesions or cancer in vertebrates. The observation that animal PV capsid-proteins spontaneously self-assemble to empty, highly immunogenic virus-like particles (VLPs) has led to the establishment of vaccines that efficiently protect humans from specific PV infections and associated diseases. We provide an overview of PV-induced tumors in horses and other equids, discuss possible routes of PV transmission in equid species, and present recent developments aiming at introducing the PV VLP-based vaccine technology...
Rotinsulu DA, Ewers C, Kerner K, Amrozi A, Soejoedono RD, Semmler T, Bauerfeind R.Strangles, caused by ssp. (), is a highly infectious and frequent disease of equines worldwide. No data are available regarding the molecular epidemiology of strangles in Indonesia. This study aimed to characterize isolates obtained from suspected strangles cases in Indonesia in 2018. Isolates originated from seven diseased horses on four different farms located in three provinces of Indonesia. Whole genome sequences of these isolates were determined and used for typing, multilocus sequence typing (MLST), and core genome MLS typing (cgMLST). Genomes were also screened for known antimicrobi...
Bannai H, Kambayashi Y, Nemoto M, Ohta M, Tsujimura K.The immune response and protective efficacy of a modified equid alphaherpesvirus 1 (EHV-1) vaccine administered by two different routes were tested in horses. Horses that received intramuscular (IM) priming and an intranasal (IN) booster with a 28-day interval (IM-IN group [n = 6]), IN priming and IM booster (IN-IM group [n = 5]), or no vaccination (control group [n = 6]) were challenged with EHV-1 strain 10-I-224 28 days after the second vaccination. Both vaccinated groups had significantly higher serum virus-neutralizing titers than the control group, with increased levels of ser...
Balena V, Pradhan SS, Bera BC, Anand T, Sansanwal R, Khetmalis R, Madhwal A, Bernela M, Supriya K, Pavulraj S, Tripathi BN, Virmani N.Equid alphaherpesvirus 1 (EHV-1) infection causes significant health problems in equines. The EHV-1 infection leads to abortion storm in mares, respiratory disease and myeloencephalopathy. Despite the wide use of vaccines, the outbreaks of EHV-1 infections keep occurring globally, suggesting the need for the development of improved vaccines. Gene deletion attenuated mutant viruses could be a good candidate for the development of modified live vaccines. Here, we report the generation of mutant EHV-1 by deleting virulence (glycoprotein E & internal repeat 6; IR6) and immune evasive (pUL43 &a...
Carnet F, Paillot R, Fortier C, Hue ES, Briot L, de Geoffroy F, Vidalain PO, Pronost S.Equine influenza virus (EIV) is responsible for recurring outbreaks that are detrimental to the equine industry. Vaccination is key for prevention, but the effectiveness and duration of protection provided by existing vaccines is often insufficient. In order to improve vaccine efficacy, we evaluated the benefit of immune stimulation with inactivated Parapoxvirus ovis (iPPVO) on the antibody response induced by a vaccine boost against EIV. A whole inactivated ISCOMatrix-adjuvanted equine influenza vaccine was administered alone ( = 10) or combined with iPPVO injections at D0, D2 and D4 post vac...
Fukushi N, Fukushi H.Equine herpesvirus type 1 (EHV-1) is a devastating pathogen of horses, their natural hosts, and causes fatal encephalitis in non-natural hosts. We previously demonstrated that acylation of the tegument protein UL11 is required for viral replication in cultured cells. We created a mutant virus (EHV-1 UL12 trunc UL11 G2AC7AC9A), in which glycyl and cysteinyl residues at positions 2, 7 and 9 of UL11 that are normally acylated were replaced with alanyl residues. This virus, designated the 2/7/9 mutant, has a limited-replication cycle (LRC), in which replication stops after just a few cycles. Here,...
Dürrwald R, Kolodziejek J, Oh DY, Herzog S, Liebermann H, Osterrieder N, Nowotny N.(1) Background: Vaccination of horses and sheep against Borna disease (BD) was common in endemic areas of Germany in the 20th century but was abandoned in the early 1990s. The recent occurrence of fatal cases of human encephalitis due to Borna disease virus 1 (BoDV-1) has rekindled the interest in vaccination. (2) Methods: The full genomes of the BD live vaccine viruses "Dessau" and "Giessen" were sequenced and analyzed for the first time. All vaccination experiments followed a proof-of-concept approach. Dose-titration infection experiments were performed in rabbits, based on both cell culture...
Thompson MA, McCann BE, Simmons RB, Rhen T.Contraceptive vaccines are used to reduce birth rates in wild and feral animal populations. While the immunocontraceptive GonaCon-Equine has proven effective in reducing fertility among female feral horses, there is individual variation in the duration of infertility following treatment. To identify genetic factors influencing the effectiveness of GonaCon-Equine, we conducted a genome-wide association study of 88 mares from a feral population genotyped using the Illumina GGP Equine 70k SNP array. Contraceptive treatment schedules and long-term foaling rates have been recorded for each individu...
Ahmed BM, Bayoumi MM, Farrag MA, Elgamal MA, Daly JM, Amer HM.Equine influenza is an important cause of respiratory disease in equids. The causative virus; EIV, is highly variable and can evolve by accumulation of mutations, particularly in the haemagglutinin (HA) gene. Currently, H3N8 is the sole subtype circulating worldwide with Florida clade 1 (FC1) is most prevalent in the Americas and FC2 in Asia and Europe. In Egypt, EIV was detected in two occasions: subtype H7N7 in 1989 and subtype H3N8 (FC1) in 2008. No data is available on the circulation pattern of EIV during the last decade despite frequent observation of suspected cases. Twenty-two nasal sw...
AbdelKhalek A, Ostafe R, Olave C, HogenEsch H, Turner JW.Immunization with porcine zona pellucida (PZP) proteins is being used successfully to induce infertility in wildlife including horses. However, widespread adoption of this method to control the growth of horse populations requires further refinement in order to induce long-term infertility, reduce the frequency and severity of injection site reactions, and make the vaccines easier to administer. The next generation of PZP-based vaccines will likely be a controlled-release formulation with different adjuvants from the Freund's adjuvants used in existing vaccines. We evaluated the response of eq...
Stefansdottir SB, Jonsdottir S, Kristjansdottir H, Svansson V, Marti E, Torsteinsdottir S.Insect bite hypersensitivity (IBH) is a seasonal dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides midges characterized by an imbalance of T-cell subsets. Iceland is free of the causative species but the prevalence of IBH in exported Icelandic horses is especially high. We have shown that intralymphatic (i.l.) vaccination with r-Culicoides allergens in Aluminum hydroxide (alum) and monophosphoryl lipid A (MPLA) adjuvants induces a desired Th1/regulatory T-cell response. The aim of this study was to compare i.l. to subcutaneous (s.c.) injection. Twelve healthy Iceland...
Gonzalez-Obando J, Forero JE, Zuluaga-Cabrera AM, Ruiz-Saenz J.Equine influenza is a highly contagious disease caused by the H3N8 equine influenza virus (EIV), which is endemically distributed throughout the world. It infects equids, and interspecies transmission to dogs has been reported. The H3N8 Florida lineage, which is divided into clades 1 and 2, is the most representative lineage in the Americas. The EIV infects the respiratory system, affecting the ciliated epithelial cells and preventing the elimination of foreign bodies and substances. Certain factors related to the disease, such as an outdated vaccination plan, age, training, and close contact ...
Alaql FA, Alhafufi AN, Kasem S, Alhammad YMO, Albaqshi H, Alyousaf A, Alsubaie FM, Alghamdi AN, Abdel-Moneim AS, Alharbi SA.Equine influenza is a major cause of respiratory infections in horses and can spread rapidly despite the availability of commercial vaccines. This study aimed to screen the incidence of equine influenza virus (EIV) and molecularly characterize the haemagglutinin and neuraminidase from positive EIV field samples collected from Saudi Arabia. Six-hundred twenty-one horses from 57 horse barns were screened for the presence of the clinical signs, suggestive for equine influenza, from different parts of Saudi Arabia. Nasopharyngeal swabs were collected from each horse showing respiratory distress. S...
Chaiyabutr N, Wattanaphansak S, Tantilerdcharoen R, Akesowan S, Ouisuwan S, Naraporn D.African horse sickness (AHS) is a non-contagious, high mortality, and insect-borne disease caused by a double-stranded RNA virus from the genus Orbivirus. The study aimed to develop inactivated vaccines serotype 1 inactivated AHS vaccine (IAV) and to compare the effect of IAV on antibody responses in young naïve horses and adult horses pre-immunized with live-attenuated AHS virus (AHSV) serotypes 1, 3, and 4 live-attenuated vaccine (LAV). Unassigned: A total of 27 horses were vaccinated in two trials. Twelve AHS naïve young horses and 15 adult horses were divided into three groups of 4 and 5...
Anna M, Łukasz M, Adam O, Chełmońska-Soyta A.The aim of the study was to investigate the mechanisms leading to immunization through the use of a multicomponent bacterial immunomodulator and to find out the relationship between the TLR 4 receptor with selected parameters of innate immunity and to acquire immunity. The study was conducted on 18 Polish Pony Horses foals divided into two study groups: control (n = 9) and experimental (n = 9). Foals from the experimental group received intramuscular duplicate injection of 5 ml of multi-component bacterial immunomodular at 35 and 40 days of age. RNA isolated from venous blood was use...
Munday JS, Knight CG, Luff JA.Papillomaviruses (PVs) are well recognized to cause pre-neoplastic and neoplastic diseases in humans. Similarly, there is increasing evidence that PVs play a significant role in the development of pre-neoplastic and neoplastic diseases of the haired skin of dogs and cats, and the mucosa of horses. As the mechanisms by which PVs cause neoplasia are well studied in humans, it is valuable to compare the PV-induced neoplasms of humans with similar PV-associated neoplasms in the companion animal species. In the second part of this comparative review, the pre-neoplastic and neoplastic diseases thoug...
Rhiner T, Fettelschoss V, Schoster A, Birkmann K, Fettelschoss-Gabriel A.Previously, virus-like particle (VLP)-based self-vaccinations targeting interleukin (IL)-5 or IL-31 have been suggested to treat equine insect bite hypersensitivity (IBH), a seasonal recurrent allergic dermatitis in horses. The IL-5-targeting equine vaccine significantly reduced blood eosinophil counts in horses, similar to human monoclonal antibodies targeting IL-5 or the IL-5 receptor alpha (IL-5Rα). Previous studies in humans have also reported an additional effect on reduction of basophil counts. The aim of the present study was to evaluate whether an equine anti-IL-5 vaccine affected blo...
Ben David A, Barnea A, Torgeman A, Diamant E, Dor E, Schwartz A, Rosen O, Caspi N, Saraf M, Lerer E, Adar Y, Lupo E, Toister E, Zichel R.Botulism is a paralytic disease caused by botulinum neurotoxins (BoNTs). Equine antitoxin is currently the standard therapy for botulism in human. The preparation of equine antitoxin relies on the immunization of horses with botulinum toxoid, which suffers from low yield and safety limitations. The Hc fragment of BoNTs was suggested to be a potent antibotulinum subunit vaccine. The current study presents a comparative evaluation of equine-based toxoid-derived antitoxin (TDA) and subunit-derived antitoxin (SDA). The potency of recombinant Hc/A, Hc/B, and Hc/E in mice was similar to that of toxo...
Camire AC, O'Bier NS, Patel DT, Cramer NA, Straubinger RK, Breitschwerdt EB, Funk RA, Marconi RT.Lyme disease (LD) is a tick-transmitted bacterial infection caused by Borreliella burgdorferi and other closely related species collectively referred to as the LD spirochetes. The LD spirochetes encode an uncharacterized family of proteins originally designated rotein amily welve (PF12). In B. burgdorferi strain B31, PF12 consists of four plasmid-carried genes, encoding BBK01, BBG01, BBH37, and BBJ08. Henceforth, we designate the PF12 proteins amily welve ipoprotein (Ftl) (FtlA) (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08). The goal of this study was to assess the potential utility o...
Arroyo LG, Hodgins DC, Guest B, Costa M, Ma Z, Monteiro MA.Clostridioides difficile (formerly Clostridium difficile) is associated with colitis in foals and mature horses. C. difficile exposes specific phosphorylated polysaccharides (PSs), named PS-I, PS-II and PS-III. These cell-surface PSs are potential vaccine targets, especially the hexasaccharide phosphate PS-II, that has been found in all C. difficile ribotypes examined. Since we previously identified anti-PS-II circulating antibodies in horses, we postulated that vaccinating foals with PS-II may prevent colonization by C. difficile. In this study, we aim to evaluate the IgM antibody response...
Marenzoni ML, De Waure C, Timoney PJ.Equid herpesvirus type 1 (EHV-1) infection can cause a range of disease syndromes of variable severity that can result in a lethal outcome and restriction of horse movements, especially in the case of outbreaks involving neurological disease. Vaccination is one of the tools used to control the infection. It is widely known that vaccination is not completely effective in ensuring protection against disease caused by this virus. In fact, the real efficacy of vaccination against EHV-1 related disease has not been measured and no systematic reviews exist on this topic. Objective: To perform a syst...
Yuen KY, Henning J, Eng MD, Wang ASW, Lenz MF, Caldwell KM, Coyle MP, Bielefeldt-Ohmann H.The increased frequency of extreme weather events due to climate change has complicated the epidemiological pattern of mosquito-borne diseases, as the host and vector dynamics shift to adapt. However, little is known about the seroprevalence of common mosquito-borne virus infections in horses in Australia. In this study, serological surveys for multiple alphaviruses were performed on samples taken from 622 horses across two horse populations (racehorses and horses residing on The University of Queensland (UQ) campus) in Queensland using the gold standard virus neutralization test. As is the ca...
Paillot R, Hannant D, Kydd JH, Daly JM.Equine influenza virus is a leading cause of respiratory disease in the horse. Equine influenza vaccines containing inactivated virus were first developed in the 1960s. Despite their intensive use, equine influenza outbreaks still continue to occur and therefore new strategies of vaccination are necessary to improve vaccine efficacy. Numerous methods of vaccination have been evaluated and commercialised in the horse, the most recent being the cold-adapted influenza virus and poxvirus-based vaccines. As a large animal model, the horse is also a useful species in which to evaluate the potential ...
Minke JM, Siger L, Karaca K, Austgen L, Gordy P, Bowen R, Renshaw RW, Loosmore S, Audonnet JC, Nordgren B.An ALVAC (canarypoxvirus)-based recombinant (vCP2017) expressing the prM and E genes derived from a 1999 New York isolate of West Nile virus (WNV) was constructed and assessed for its protective efficacy in horses in two different experiments. In the first trial, a dose titration study was conducted to evaluate both serum neutralising antibody responses to WNV and duration of immunity. In the second trial the onset of protection was determined. Twenty-eight adult horses received two doses of vCP2017 administered intramuscularly at 5-week intervals and sixteen horses comprised age-matched non-v...
Daly JM, MacRae S, Newton JR, Wattrang E, Elton DM.This review discusses some of the challenges still faced in the control of equine influenza virus H3N8 infection. A widespread outbreak of equine influenza in the United Kingdom during 2003 in vaccinated Thoroughbred racehorses challenged the current dogma on vaccine strain selection. Furthermore, several new developments in the first decade of the 21st century, including transmission to and establishment in dogs, a presumed influenza-associated encephalopathy in horses and an outbreak of equine influenza in Australia, serve as a reminder of the unpredictable nature of influenza viruses. The a...
Goehring LS, Wagner B, Bigbie R, Hussey SB, Rao S, Morley PS, Lunn DP.Equine herpesvirus-1 is a cause of outbreaks of abortion and neurological disease. The pathogenesis of both these diseases depends on establishment of viremia. An experiment was performed to determine the protective efficacy of two commercially available vaccines used with an optimized 3-dose vaccination regime: a modified-live viral (MLV) and a high antigen load killed vaccine licensed for abortion control. The study design was a blinded, randomized challenge trial. Three groups of 8 yearling ponies received one of three treatments: MLV vaccine (Rhinomune, Boehringer Ingelheim Vetmedica, Inc....
Issel CJ, Horohov DW, Lea DF, Adams WV, Hagius SD, McManus JM, Allison AC, Montelaro RC.We report here on a series of vaccine trials to evaluate the effectiveness of an inactivated equine infectious anemia virus (EIAV) whole-virus vaccine and of a subunit vaccine enriched in EIAV envelope glycoproteins. The inactivated vaccine protected 14 of 15 immunized ponies from infection after challenge with at least 10(5) 50% tissue culture-infective doses of the homologous prototype strain of EIAV. In contrast, it failed to prevent infection in any of 15 immunized ponies that were challenged with the heterologous PV strain. Levels of PV virus replication and the development of disease, ho...
van der Geize R, Grommen AW, Hessels GI, Jacobs AA, Dijkhuizen L.Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis vi...
Kydd JH, Townsend HG, Hannant D.Equine herpesvirus-1 (EHV-1) is an alphaherpesvirus which infects horses, causing respiratory and neurological disease and abortion in pregnant mares. Latency is established in trigeminal ganglia and lymphocytes. Immunity to EHV-1 lasts between 3 and 6 months. Current vaccines, many of which contain inactivated virus, have reduced the incidence of abortion storms in pregnant mares but individual animals, which may be of high commercial value, remain susceptible to infection. The development of effective vaccines which stimulate both humoral and cellular immune responses remains a priority. Uti...
Fettelschoss-Gabriel A, Fettelschoss V, Thoms F, Giese C, Daniel M, Olomski F, Kamarachev J, Birkmann K, Bühler M, Kummer M, Zeltins A, Marti E....Insect-bite hypersensitivity is the most common allergic dermatitis in horses. Excoriated skin lesions are typical symptoms of this seasonal and refractory chronic disease. On a cellular level, the skin lesions are characterized by massive eosinophil infiltration caused by an underlying allergic response. To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils. The vaccine consisted of eIL-5 covalently linked to a virus-like particle derived from cucumber mosaic virus containing the tetanus toxoid universal T-...
Fukunaga Y, Kumanomido T, Kamada M.Getah virus is a member of the genus Alphavirus in the family Togaviridae and has been frequently isolated from mosquitoes. Seroepizootiologic studies indicate that the virus is mosquito-borne and widespread, ranging from Eurasia to southeast and far eastern Asia, the Pacific islands, and Australasia. The natural host animal of the virus was not known until the first recognized occurrence of Getah virus infection among racehorses in two training centers in Japan in 1978. Outbreaks of clinical disease due to Getah virus infection occur infrequently, and only one outbreak has been reported outsi...
Kelly C, Bugg M, Robinson C, Mitchell Z, Davis-Poynter N, Newton JR, Jolley KA, Maiden MC, Waller AS.Improved understanding of the epidemiology of Streptococcus equi transmission requires sensitive and portable subtyping methods that can rationally discriminate between strains. S. equi is highly homogeneous and cannot be distinguished by multilocus enzyme electrophoretic or multilocus sequence-typing methods that utilize housekeeping genes. However, on sequence analysis of the N-terminal region of the SeM genes of 60 S. equi isolates from 27 strangles outbreaks, we identified 21 DNA codon changes. These resulted in the nonsynonymous substitution of 18 amino acids and allowed the assignment of...
Lu J, Guo Z, Pan X, Wang G, Zhang D, Li Y, Tan B, Ouyang L, Yu X.Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab')2 fragments by pepsin digestion of IgGs. Methods: The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab')2 fragments were p...
Paillot R.Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strateg...
Guthrie AJ, Quan M, Lourens CW, Audonnet JC, Minke JM, Yao J, He L, Nordgren R, Gardner IA, Maclachlan NJ.We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contra...
Ledizet M, Kar K, Foellmer HG, Wang T, Bushmich SL, Anderson JF, Fikrig E, Koski RA.West Nile (WN) virus is a flavivirus that first appeared in North America in 1999. Since then, more than 600 human deaths and 22,000 equine infections have been attributed to the virus in the United States. We expressed a truncated form of WN virus envelope (E) protein in Drosophila S2 cells. This soluble recombinant E protein was recognized by antibodies from naturally infected horses, indicating that it contains native epitopes. Mice and horses produced high-titer antibodies when immunized with recombinant E protein combined with aluminum hydroxide. Immunized mice were resistant to challenge...
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...
Weaver SC, Pfeffer M, Marriott K, Kang W, Kinney RM.Epizootics of Venezuelan equine encephalitis (VEE) involving subtype IAB viruses occurred sporadically in South, Central and North America from 1938 to 1973. Incompletely inactivated vaccines have long been suspected as a source of the later epizootics. We tested this hypothesis by sequencing the PE2 glycoprotein precursor (1,677 nucleotides) or 26S/nonstructural protein 4 (nsP4) genome regions (4,490 nucleotides) for isolates representing most major outbreaks. Two distinct IAB genotypes were identified: 1) 1940s Peruvian strains and 2) 1938-1973 isolates from South, Central, and North America...
Ball JM, Rushlow KE, Issel CJ, Montelaro RC.We describe here a detailed analysis of the antigenic determinants of the surface unit glycoprotein (gp90) of equine infectious anemia virus (EIAV), using a comprehensive panel of synthetic peptides in enzyme-linked immunosorbent assays with immune serum from naturally and experimentally infected horses and with a panel of gp90-specific neutralizing and nonneutralizing monoclonal antibodies. The results of these studies identify immunoreactive segments throughout the conserved and variable domains of gp90 but localize immunodominant (100% reactivity) determinants to the amino and carboxyl term...
Hannaman D, Dupuy LC, Ellefsen B, Schmaljohn CS.Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP gro...
de la Rosa G, Olvera F, Archundia IG, Lomonte B, Alagón A, Corzo G.Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immu...
Bryant NA, Wilkie GS, Russell CA, Compston L, Grafham D, Clissold L, McLay K, Medcalf L, Newton R, Davison AJ, Elton DM.Equine herpesvirus 1 (EHV-1) causes respiratory disease, abortion, neonatal death and neurological disease in equines and is endemic in most countries. The viral factors that influence EHV-1 disease severity are poorly understood, and this has hampered vaccine development. However, the N752D substitution in the viral DNA polymerase catalytic subunit has been shown statistically to be associated with neurological disease. This has given rise to the term "neuropathic strain," even though strains lacking the polymorphism have been recovered from cases of neurological disease. To broaden understan...
Timoney PJ.A highly contagious virus infection of horses, influenza is the single most important equine respiratory disease in many countries. Two subtypes of equine influenza virus have been identified, A/equine-1 and A/equine-2, neither of which immunologically cross-reacts. In the case of A/equine-2 virus, two lineages exist, American and European, which appear to have evolved independently of one another. The acute febrile respiratory disease characteristic of influenza is frequently complicated by secondary bacterial infection, especially in unvaccinated horses. Primarily a respiratory-borne infecti...
van Maanen C.Equine herpesvirus 1 (EHV1) and equine herpesvirus 4 (EHV4) are important ubiquitous equine viral pathogens, causing much damage to the horse industry. EHV1 strains are associated with respiratory disease, abortion, and paresis/paralysis, whereas EHV4 strains are predominantly associated with respiratory disease. In the past decades much research effort has been put into improving knowledge about these viruses. In this paper the current state of knowledge of these viruses and the most important aspects of these virus infections, e.g. epidemiology, clinical aspects, pathogenesis and pathology, ...
Aréchiga-Ceballos N, Aguilar-Setién A.Summary Alphaviral equine encephalomyelitis is a mosquito-borne infection that causes severe neurological disease and fatalities in horses and humans in the Americas. Consequently, the equine alphaviruses (Eastern, Western and Venezuelan) are of considerable concern worldwide and are notifiable to the World Organisation for Animal Health. In addition, these diseases are considered a potent potential biological weapon, emphasising the need to develop an effective vaccine. Alphaviral equine encephalomyelitis is caused by Eastern equine encephalomyelitis virus (EEEV), Western equine encephalomyel...
Chang DC, Liu WJ, Anraku I, Clark DC, Pollitt CC, Suhrbier A, Hall RA, Khromykh AA.DNA vaccines encoding replication-defective viruses are safer than inactivated or live attenuated viruses but may fail to stimulate an immune response sufficient for effective vaccination. We augment the protective capacity of a capsid-deleted flavivirus DNA vaccine by co-expressing the capsid protein from a separate promoter. In transfected cells, the capsid-deleted RNA transcript is replicated and translated to produce secreted virus-like particles lacking the nucleocapsid. This RNA is also packaged with the help of co-expressed capsid protein to form secreted single-round infectious particl...
Cullinane A, Elton D, Mumford J.Equine influenza virus (EIV) is considered the most important respiratory virus of horses because it is highly contagious and has the potential to disrupt major equestrian events. Equine influenza (EI) can be controlled by vaccination but it has been demonstrated repeatedly in the field that antigenic drift impacts on vaccine efficacy. EI surveillance maintains awareness of emergence and international spread of antigenic variants. It not only serves as an early warning system for horse owners, trainers and veterinary clinicians but is fundamental to influenza control programmes based on vaccin...
Poulet H, Minke J, Pardo MC, Juillard V, Nordgren B, Audonnet JC.The canarypox vaccine vector (ALVAC) technology has been used to develop and license several vaccines for companion animals and horses in the European Union and USA. ALVAC is a ubiquitous vector with high biosafety since it is non-replicative in mammalians, is genetically and physically stable, and able to induce both humoral and cell-mediated immune responses against the expressed transgene product. Specific rules apply for the development and registration of recombinant vector vaccines. The biology of the vector as well as the recombinant virus must be thoroughly documented to allow the risk...
Manole V, Laurinmäki P, Van Wyngaardt W, Potgieter CA, Wright IM, Venter GJ, van Dijk AA, Sewell BT, Butcher SJ.African horsesickness (AHS) is a devastating disease of horses. The disease is caused by the double-stranded RNA-containing African horsesickness virus (AHSV). Using electron cryomicroscopy and three-dimensional image reconstruction, we determined the architecture of an AHSV serotype 4 (AHSV-4) reference strain. The structure revealed triple-layered AHS virions enclosing the segmented genome and transcriptase complex. The innermost protein layer contains 120 copies of VP3, with the viral polymerase, capping enzyme, and helicase attached to the inner surface of the VP3 layer on the 5-fold axis,...
Yuen KY, Fraser NS, Henning J, Halpin K, Gibson JS, Betzien L, Stewart AJ.Hendra virus (HeV) continues to pose a serious public health concern as spillover events occur sporadically. Terminally ill horses can exhibit a range of clinical signs including frothy nasal discharge, ataxia or forebrain signs. Early signs, if detected, can include depression, inappetence, colic or mild respiratory signs. All unvaccinated ill horses in areas where flying foxes exist, may potentially be infected with HeV, posing a significant risk to the veterinary community. Equivac® HeV vaccine has been fully registered in Australia since 2015 (and under an Australian Pesticides and Veteri...
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)...
Wang SZ, Rushlow KE, Issel CJ, Cook RF, Cook SJ, Raabe ML, Chong YH, Costa L, Montelaro RC.The potential for antibody-dependent enhancement of replication of macrophage/monocyte tropic viruses has posed a significant problem in the development of vaccines for several animal and human viruses and has raised significant concern in the design of potential AIDS vaccines. Using the previously described equine infectious anemia virus/Shetland pony system as a model for HIV-1 vaccine development, we have evaluated the efficacy of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. The results of these trials demonstrate not only th...
