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.
McNabb L, McMahon A, Woube EG, Agnihotri K, Colling A, Broder CC, Kucinskaite-Kodze I, Petraityte-Burneikiene R, Bowden TR, Halpin K.Hendra virus (HeV) is a bat-borne zoonotic agent which can cause a severe and highly fatal disease and can be transferred from animals to humans. It has caused over 100 deaths in horses since it was discovered in 1994. Four out of seven infected humans have died. Since the release of the HeV vaccine (Equivac® HeV Hendra Virus Vaccine for Horses, Zoetis Australia Pty Ltd., Rhodes, NSW 2138) in Australia, there has been an urgent requirement for a serological test for differentiating infected from vaccinated animals (DIVA). All first-line diagnostic serological assays at the Australian Centre f...
In February 2021, a serious EHV-1 outbreak occurred at an international jumping competition in Valencia, with several subsequent outbreaks in various European countries. As a consequence, several equestrian associations introduced compulsory vaccination against EHV-1, and in the immediate aftermath of the outbreak, demand for EHV vaccinations increased sharply. The initial concern has now dissipated. One equestrian association has abolished the compulsory vaccination that had only been introduced a year before, and a general debate began questioning the efficacy and safety of EHV-vaccines. Thi...
Vaccination is one of the most important measures for preventing infectious diseases. Vaccinations against tetanus and West-Nile-Virus are essential to protect the individual horse. These infections are not contagious and are not transmitted from animal to animal. By contrast, Equine Influenza and Equine-Herpes-Virus infections are highly contagious, transmissible diseases. In addition to protecting the vaccinated individual, vaccinating as many horses as possible aims at inducing a broad herd immunity, which interrupts infection chains and thus additionally protects the individual. Vaccinatio...
O'Kennedy MM, Reedy SE, Abolnik C, Khan A, Smith T, du Preez I, Olajide E, Daly J, Cullinane A, Chambers TM.Equine influenza (EI) is a highly contagious acute respiratory disease of wild and domesticated horses, donkeys, mules, and other Equidae. EI is caused by the Equine Influenza virus (EIV), is endemic in many countries and outbreaks still have a severe impact on the equine industry globally. Conventional EI vaccines are widely used, but a need exists for a platform that facilitates prompt manufacturing of a highly immunogenic, antigenically matched, updated vaccine product. Here we developed a plant-produced bivalent EI virus-like particle (VLP) vaccine candidate which lacks the viral genome an...
Jacob O, Hause B, Peters-Smith K, Adam EN, Page AE, Floyd C, Tucker C, Eertink LG, Wang D, Li F.Equine sarcoids are the most identified skin tumors of horses, which are highly associated with bovine papillomavirus infection. Sarcoids can impair the use of the horse and are difficult to treat, resulting in significant economic losses and a welfare concern. There is no vaccine available to protect global equines from sarcoids. We aimed to determine the safety and protective antibody response in horses immunized with a recombinant baculovirus vector vaccine expressing the L1 protein of bovine papillomavirus type 1 (BPV1). A group of 10 clinically healthy, sarcoid-free horses were immunized ...
Amirkhani A, Karami-Mohajeri S, Heidari MR, Amirheidari B, Mandegary A, Hosseininejad-Chafi M, Khalili-Salmasi M, Tavangarroosta S....Scorpion envenomation, especially from Hemiscorpius lepturus, poses a significant health risk, leading to considerable morbidity and mortality. The venom's major toxin, which includes phospholipase D (PLD), is responsible for various systemic complications. In prior studies, we identified a native phospholipase D (PLD) toxin as a key lethal factor in the venom of H. lepturus. A recombinant PLD that retained its toxicity was developed and designated as PLD1. Additionally, a non-toxic and devoid of lethal effects mutant form of the recombinant PLD1 protein, was produced and named as mPLD1. Build...
Parashar B, Malviya R, Sridhar SB, Wadhwa T, Talath S, Shareef J.Eastern equine encephalitis virus (EEEV) is a lethal transmitted by mosquitoes that primarily cycles between birds. Although rare, infections in humans and horses are associated with high mortality rates and severe neurological effects. Climate change appears to be increasing the spread of this virus. This study aims to provide a comprehensive analysis of EEEV, including its transmission dynamics, pathogenesis, induced host immune response, and long-term impacts on survivors. It also highlights the virus's unique immune evasion strategies that complicate disease management and contribute to ...
Pradhan SS, Balena V, Bera BC, Anand T, Khetmalis R, Madhwal A, Kandasamy S, Pavulraj S, Bernela M, Mor P, Tripathi BN, Virmani N.Equine herpesvirus type 1 (EHV1) is a ubiquitous viral pathogen infecting the equine population worldwide. EHV1 infection causes respiratory illness, abortion, neonatal foal mortality, and myeloencephalopathy. The currently available modified live EHV1 vaccines have safety and efficacy limitations. The two mutant EHV1 viruses (vToH-DMV (∆IR6/gE) and vToH-QMV (∆IR6/UL43/gE/UL56)), generated by the deletion of genes responsible for virulence (gE and IR6) and immunosuppression (uL43 and uL56), have been previously characterized by our group and found to generate good immune responses. The pre...
Ma AZ, Yeo YY, Lee JF, Kim CM, Ezzatpour S, Menchaca C, Upadhye V, Annand EJ, Eden J-S, Plowright RK, Peel AJ, Buchholz DW, Aguilar HC.A novel Hendra virus (HeV) genotype (HeV genotype 2 [HeV-g2]) was recently isolated from a deceased horse, revealing high-sequence conservation and antigenic similarities with the prototypic strain, HeV-g1. As the receptor-binding (G) and fusion (F) glycoproteins of HeV are essential for mediating viral entry, functional characterization of emerging HeV genotypic variants is key to understanding viral entry mechanisms and broader virus-host co-evolution. We first confirmed that HeV-g2 and HeV-g1 glycoproteins share a close phylogenetic relationship, underscoring HeV-g2's relevance to global he...
Verhoeven D, Sponseller BA, Crowe JE, Bangaru S, Webby RJ, Lee BM.Development of an efficacious universal influenza vaccines remains a long-sought goal. Current vaccines have shortfalls such as mid/low efficacy and needing yearly strain revisions to account for viral drift/shift. Horses undergo bi-annual vaccines for the H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many influenza strains. Subsequently, vaccinating mice using the equine A/Kentucky/1/1991 strain or recombinant hemagglutinin (HA) induced similar broadly reactive and neutralizing antibodies to seasonal and high path...
Carrasco L, Utrilla MJ, Fuentes-Romero B, Fernandez-Novo A, Martin-Maldonado B.West Nile Virus (WNV) is a zoonotic, vector-borne pathogen affecting humans and animals, particularly in Europe. The virus is primarily transmitted through mosquitoes that infect birds, which serve as the main reservoirs. Humans and horses are incidental hosts. This review focuses on the epidemiology of WNV in southern Europe, particularly its increasing prevalence. Methods included an extensive literature review and analysis of recent outbreaks. WNV is largely asymptomatic in humans, but a small percentage can develop West Nile neuroinvasive disease (WNND), leading to severe neurological symp...
Cohen ND, Hughes EV, Bayne C, Morris ERA, Bray JM, Landrock KK, Gonzales DM, Baker RM, Klein RL, Liu W, Legere RM, Wehmeyer SG, Bordin AI....Evaluate the immunogenicity of a vaccine targeting the S protein (Ssee) of Streptococcus equi subsp equi and determine antibody activity against Ssee in horses with strangles. Methods: The study was designed as a prospective experiment using 20 university-owned Quarter Horses and a cross-sectional serosurvey of 78 privately owned horses with strangles. Horses were immunized IM with 0 (n = 4), 200 (n = 8), or 400 (n = 8) μg of recombinant Ssee at weeks 0, 4, and 12. Serum and nasal secretions were collected at weeks 0, 4, 6, 12, 16, and 28 and tested by ELISA for immunoglobulin (Ig)-G against ...
Cohen ND, Hughes EV, Bayne C, Morris ERA, Bray JM, Landrock KK, Gonzales DM, Baker RM, Klein RL, Liu W, Legere RM, Wehmeyer SG, Bordin AI....Evaluate the immunogenicity of a vaccine targeting the S protein (Ssee) of Streptococcus equi subsp equi and determine antibody activity against Ssee in horses with strangles. Methods: The study was designed as a prospective experiment using 20 university-owned Quarter Horses and a cross-sectional serosurvey of 78 privately owned horses with strangles. Horses were immunized IM with 0 (n = 4), 200 (n = 8), or 400 (n = 8) μg of recombinant Ssee at weeks 0, 4, and 12. Serum and nasal secretions were collected at weeks 0, 4, 6, 12, 16, and 28 and tested by ELISA for immunoglobulin (Ig)-G against ...
Matsumura R, Bannai H, Nemoto M, Higa Y, Kai I, Sasaki T, Futami K, Yoshikawa A, Fujita R, Hino M, Nagata K, Kuwata R, Kaku Y, Kobayashi D....Getah virus (GETV), belonging to the genus Alphavirus within the family Togaviridae, is a mosquito-borne virus that causes fever, rash, edema in horses, fatalities, and pregnancy disorders in pigs. It has caused occasional outbreaks in horse populations in Japan, China, and India, and the endemic areas are gradually expanding, particularly in Asia and Oceania. In this study, we isolated a new GETV strain from Culex tritaeniorhynchus mosquitoes collected in Nagasaki Prefecture, Japan, in 2022. Phylogenetic analysis demonstrated that this new strain, 22IH8, was more closely related to previous C...
Jiang Z, Merits A, Qin Y, Xing G, Zhang L, Chen J, Wang N, Varjak M, Zhai X, Li D, Song W, Su S.Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of G...
Pooja , Thapa N, Rani R, Shanmugasundaram K, Jhandai P, Rakshita , Bhattacharya TK, Singha H.Immunological aspects of B. mallei infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum. Methods: The study was conducted on serum samples collected from 151 glanders positive equines which include horses (n = 134), mules (n = 16), and donkeys (n = 01). The IgM, IgG, IgA and IgG (T) titre were determined against recombinant antigens by indirect E...
Sánchez A, Durán G, Cerdas M, Gutiérrez J, Segura Á, Herrera M, Vargas M, Sánchez A, Sánchez P, Solano G, Villalta M, Moscoso E, Umaña D....Recent research suggests that a polygeneric immunogen made from the venoms of the most medically important viperid and elapid snakes in sub-Saharan Africa could elicit a broader antibody response in horses compared to the current EchiTAb-plus-ICP antivenom, especially against neurotoxic elapid venoms. To test this, 25 horses that have been regularly immunized to produce this antivenom were reimmunized with an immunogen containing 22 venoms from various snake species from the genera , , , and both spitting and non-spitting . The plasma collected from these horses was processed using the capryli...
Frontiers in allergySeptember 30, 2024
Volume 5 1467245 doi: 10.3389/falgy.2024.1467245
Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S, Marti E.Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis of horses caused by bites of spp., sharing some common features with human atopic dermatitis. Allergen immunotherapy (AIT) using whole-body extracts has limited efficacy. This study aimed to evaluate AIT with a pool of major recombinant allergens in a prospective, double-blinded, placebo-controlled study. Unassigned: The IBH lesion score was assessed during a pre-treatment year and first treatment year (May-October) in 17 horses and in May and July of a second treatment year. Nine horses were immunized subcutaneously ...
Lin Y, Wang Y, Li H, Liu T, Zhang J, Guo X, Guo W, Wang Y, Liu X, Huang S, Liao H, Wang X.Single B cells-based antibody platforms offer an effective approach for the discovery of useful antibodies for therapeutic or research purposes. Here we present a method for screening equine immunoglobins F(ab)2, which offers the potential advantage of reacting with multiple epitopes on the virus. Using equine influenza virus (EIV) as model, a hemagglutinin (HA) trimer was constructed to bait B cells in vaccinated horses. We screened 370 HA-specific B cells from 1 × 10 PBMCs and identified a diverse set of equine variable region gene sequences of heavy and light chains and then recombined wit...
Yang HW, Hu T, Ait-Ali T.Lawsonia intracellularis is the etiological agent of proliferative enteropathy (PE) in pigs, horses and wide range of mammals. Little is known about the role of innate immune response during L. intracellularis infection. In this study, we investigated the nuclear factor-κB (NF-κB)-regulated immune response against infection of a clinical strain Dkp23 and a live-attenuated Enterisol vaccine strain in PK-15 cells. We found that expression of NF-κB target genes TNF-α, IFN-γ, IL-6 and IL-8 were modulated during the course of infection. At 5 dpi, there was a significant increase in p65 NF-κB ...
Hu X, Xu J, Wang X, Tian Z, Guan G, Luo J, Yin H, Du J.African horse sickness (AHS) is an acute and subacute infectious disease of equine species caused by the African horse sickness virus (AHSV). The VP7 of AHSV is a group-specific protein conserved in all serotypes and is an excellent candidate for the serological diagnosis and an AHS vaccine component. However, to date, B-cell epitopes on the AHSV VP7 recognized by humoral immune responses remain unclear. This study expressed the recombinant AHSV VP7 soluble in Escherichia coli and purified it for mouse immunization. Four monoclonal antibodies (mAbs) were screened and identified by hybridoma ce...
Hu Y, Zhang SY, Sun WC, Feng YR, Gong HR, Ran DL, Zhang BZ, Liu JH.Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and vali...
da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI.Rhodococcus equi causes pyogranulomatous pneumonia in foals and immunocompromised people. Despite decades of research efforts, no vaccine is available against this common cause of disease and death in foals. The purpose of this narrative review is to summarise the current understanding of interactions between R. equi and the host innate immune system, to describe features of the immune response that are associated with resistance or susceptibility to R. equi infection, and help guide strategies for developing novel approaches for preventing R. equi infections. Virulence of R. equi in foals has...
Kasem S, Yu MHH, Alkhalefa N, Ata EB, Nayel M, Abdo W, Abdel-Moneim AS, Fukushi H.Equine herpesvirus 1 (EHV-1) causes respiratory illness, fetal loss, perinatal mortality, and myeloencephalopathy. This study investigated ORF15's impact on virus infectivity and neurovirulence. The Ab4p neurovirulent strain of EHV1 was used as a backbone to create Ab4p attB, Ab4p∆ORF15, and Ab4p∆ORF15R chimeras via BAC DNA transfection into RK-13 cells. Viral growth kinetics, plaque size, transcription, and growth were assessed in MDBK cells, mouse neurons, and fetal equine brain cells. Neurovirulence was evaluated post-intranasal inoculation into male CBA/N1 SPF mice, measuring signs, vi...
Holmes CM, Babasyan S, Eady N, Schnabel CL, Wagner B.Equine herpesvirus type 1 (EHV-1) is one of the most prevalent respiratory pathogens in horses with a high impact on animal health worldwide. Entry of the virus into epithelial cells of the upper respiratory tract and rapid local viral replication is followed by infection of local lymphoid tissues leading to cell-associated viremia and disease progression. Pre-existing mucosal immunity has previously been shown to reduce viral shedding and prevent viremia, consequently limiting severe disease manifestations. Here, nasopharyngeal transcriptomic profiling was used to identify differentially expr...
Li W, Plante JA, Lin C, Basu H, Plung JS, Fan X, Boeckers JM, Oros J, Buck TK, Anekal PV, Hanson WA, Varnum H, Wells A, Mann CJ, Tjang LV, Yang P....Western equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) that frequently caused major outbreaks of encephalitis in humans and horses in the early twentieth century, but the frequency of outbreaks has since decreased markedly, and strains of this alphavirus isolated in the past two decades are less virulent in mammals than strains isolated in the 1930s and 1940s. The basis for this phenotypic change in WEEV strains and coincident decrease in epizootic activity (known as viral submergence) is unclear, as is the possibility of re-emergence of highly virulent strains. Here...
Schramm A, Ackermann M, Eichwald C, Aguilar C, Fraefel C, Lechmann J.Equid alphaherpesviruses 1 (EHV-1) and 4 (EHV-4) are closely related and both endemic in horses worldwide. Both viruses replicate in the upper respiratory tract, but EHV-1 may additionally lead to abortion and equine herpesvirus myeloencephalopathy (EHM). We focused on antibody responses in horses against the receptor-binding glycoprotein D of EHV-1 (gD1), which shares a 77% amino acid identity with its counterpart in EHV-4 (gD4). Both antigens give rise to cross-reacting antibodies, including neutralizing antibodies. However, immunity against EHV-4 is not considered protective against EHM. Wh...
Liu L, Cai P, Gu W, Duan X, Gao S, Ma X, Ma Y, Ma S, Li G, Wang X, Cai K, Wang Y, Cai T, Zhao H.Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were se...
Hu Y, Wu G, Jia Q, Zhang B, Sun W, Sa R, Zhang S, Cai W, Jarhen , Ran D, Liu J.Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of...
Field HE.Hendra virus causes acute and highly fatal infection in horses and humans. Pteropid bats (flying-foxes) are the natural host of the virus, with age and species being risk factors for infection. Urine is the primary route of excretion in flying-foxes, with viral RNA more frequently detected in Pteropus alecto and P. conspicillatus than other species. Infection prevalence in flying-foxes can vary between and within years, with a winter peak of excretion occurring in some regions. Vertical transmission and recrudescing infection has been reported in flying-foxes, but horizontal transmission is ev...
Nara PL, Garrity RR, Goudsmit J.The production of immunoglobulin capable of neutralizing the infectivity of a virus represents one of the most remarkable molecular accomplishments of the host's available immune defenses. It should be no surprise that a virus that has existed in the parenchyma of the immune system has evolved as an equally dynamic molecule (i.e., viral envelope) for survival. Neutralizing immunoglobulin (Ig) can best serve the host under conditions where the invading pathogen requires a well-defined cell-free state for establishing an infection or transmission. Evidence for a controlling and therefore protect...
McLean RG, Ubico SR, Bourne D, Komar N.WN virus is one of the most ubiquitous arboviruses occurring over a broad geographical range and in a wide diversity of vertebrate host and vector species. The virus appears to be maintained in endemic foci on the African continent and is transported annually to temperate climates to the north in Europe and to the south in South Africa. Reports of clinical disease due to natural WN virus infection in wild or domestic animals were much less common than reports of infection (virus isolation or antibody detection). Until recently, records of morbidity and mortality in wild birds were confined to ...
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...
Ma G, Azab W, Osterrieder N.The equine herpesviruses type 1 (EHV-1) and 4 (EHV-4) are ubiquitous pathogens that affect horse populations on all continents. Despite widespread vaccination, EHV-1 and EHV-4 infections remain a permanent risk. While the two viruses share a high degree of genetic and antigenic similarity, they differ significantly in host range and pathogenicity. Compared to EHV-4, which mainly infects horses and causes respiratory disease, EHV-1 has a broader host range and can result in respiratory disease, abortions, neonatal death, and equine herpesvirusmyeloencephalopathy (EHM). Recent studies have eluci...
El Garch H, Minke JM, Rehder J, Richard S, Edlund Toulemonde C, Dinic S, Andreoni C, Audonnet JC, Nordgren R, Juillard V.Successful vaccination against West Nile virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine. The results demonstrated that the recombinant ALVAC-WNV va...
David S, Abraham AM.Since the isolation of West Nile virus (WNV) in 1937, in Uganda, it has spread globally, causing significant morbidity and mortality. While birds serve as amplifier hosts, mosquitoes of the Culex genus function as vectors. Humans and horses are dead end hosts. The clinical manifestations of West Nile infection in humans range from asymptomatic illness to West Nile encephalitis. Methods: The laboratory offers an array of tests, the preferred method being detection of RNA and serum IgM for WNV, which, if detected, confirms the clinical diagnosis. Although no definitive antiviral therapy and vacc...
Dennis SJ, Meyers AE, Hitzeroth II, Rybicki EP.African horse sickness is a devastating disease that causes great suffering and many fatalities amongst horses in sub-Saharan Africa. It is caused by nine different serotypes of the orbivirus African horse sickness virus (AHSV) and it is spread by Culicoid midges. The disease has significant economic consequences for the equine industry both in southern Africa and increasingly further afield as the geographic distribution of the midge vector broadens with global warming and climate change. Live attenuated vaccines (LAV) have been used with relative success for many decades but carry the risk o...
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...
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...
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...
Liu G, Cao W, Salawudeen A, Zhu W, Emeterio K, Safronetz D, Banadyga L.Vesicular stomatitis virus (VSV), which belongs to the Vesiculovirus genus of the family Rhabdoviridae, is a well studied livestock pathogen and prototypic non-segmented, negative-sense RNA virus. Although VSV is responsible for causing economically significant outbreaks of vesicular stomatitis in cattle, horses, and swine, the virus also represents a valuable research tool for molecular biologists and virologists. Indeed, the establishment of a reverse genetics system for the recovery of infectious VSV from cDNA transformed the utility of this virus and paved the way for its use as a vaccine ...
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...
Kirkpatrick JF, Lyda RO, Frank KM.Wildlife, free-ranging and captive, poses and causes serious population problems not unlike those encountered with human overpopulation. Traditional lethal control programs, however, are not always legal, wise, safe, or publicly acceptable; thus, alternative approaches are necessary. Immunocontraception of free-ranging wildlife has reached the management level, with success across a large variety of species. Thus far, the immunocontraceptive research and management applications emphasis have been centered on porcine zona pellucida and gonadotropin-releasing hormone vaccines. Contraceptive succ...
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...
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...
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...
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...
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...
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...
Harris SR, Robinson C, Steward KF, Webb KS, Paillot R, Parkhill J, Holden MT, Waller AS.Strangles, the most frequently diagnosed infectious disease of horses worldwide, is caused by Streptococcus equi. Despite its prevalence, the global diversity and mechanisms underlying the evolution of S. equi as a host-restricted pathogen remain poorly understood. Here, we define the global population structure of this important pathogen and reveal a population replacement in the late 19th or early 20th Century. Our data reveal a dynamic genome that continues to mutate and decay, but also to amplify and acquire genes despite the organism having lost its natural competence and become host-rest...
Turner CE, Kurupati P, Wiles S, Edwards RJ, Sriskandan S.Currently there is no licensed vaccine against the human pathogen Streptococcus pyogenes. The highly conserved IL-8 cleaving S. pyogenes cell envelope proteinase SpyCEP is surface expressed and is a potential vaccine candidate. A recombinant N-terminal part of SpyCEP (CEP) was expressed and purified. AntiCEP antibodies were found to neutralize the IL-8 cleaving activity of SpyCEP. CEP-immunized mice had reduced bacterial dissemination from focal S. pyogenes intramuscular infection and intranasal infection. We also identified a functional SpyCEP-homolog protease SeCEP, expressed by the equine p...
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...
Woodward AL, Rash AS, Blinman D, Bowman S, Chambers TM, Daly JM, Damiani A, Joseph S, Lewis N, McCauley JW, Medcalf L, Mumford J, Newton JR, Tiwari A....Equine influenza viruses are a major cause of respiratory disease in horses worldwide and undergo antigenic drift. Several outbreaks of equine influenza occurred worldwide during 2010-2012, including in vaccinated animals, highlighting the importance of surveillance and virus characterisation. Virus isolates were characterised from more than 20 outbreaks over a 3-year period, including strains from the UK, Dubai, Germany and the USA. The haemagglutinin-1 (HA1) sequence of all isolates was determined and compared with OIE-recommended vaccine strains. Viruses from Florida clades 1 and 2 showed c...
