Immunization in horses involves the administration of vaccines to stimulate an immune response, thereby providing protection against specific infectious diseases. Vaccines commonly used in equine medicine include those for equine influenza, tetanus, and West Nile virus. The process of immunization aims to prepare the horse's immune system to recognize and combat pathogens upon exposure. Vaccination schedules and protocols may vary based on factors such as age, health status, and regional disease prevalence. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, efficacy, and considerations of immunization practices in equine health.
Conrad NL, Mazzoleni I, Abreu MC, Costa AV, Di Giácomo CP, Zorzi VSG, Leite FPL.Equine proliferative enteropathy (EPE), caused by Lawsonia intracellularis induces intestinal epithelial hyperplasia, resulting in malabsorption, weight loss, colic, and diarrhea. Despite its clinical and economic importance, no equine-specific vaccine is commercially available. Recombinant subunit vaccines are a safe and scalable alternative; however, their immunogenicity often requires improvement. Probiotic supplementation with Bacillus toyonensis may act as an immunomodulatory strategy to potentiate vaccine efficacy. This study aimed to evaluate the immunogenicity of a recombinant protein ...
Acevedo-Jiménez GE, Morales-González C, Akbarin MM, Rodríguez-Murillo C, González-Fernández VD, Avila-De la Vega LM, García-Flores MM....Equine infectious anemia virus (EIAV) is a globally significant equine pathogen, and its control relies on effective serological surveillance. The agar gel immunodiffusion (AGID) test, the WOAH-prescribed method, has limitations in sensitivity. This study developed and validated an indirect ELISA using a synthetic peptide derived from a conserved region of the EIAV gp90 surface glycoprotein. The assay was evaluated using 773 horse sera from the Metropolitan Zone of the Valley of Mexico and compared to the AGID test. The gp90-EIAV ELISA demonstrated a sensitivity of 85.3 % and a specificity o...
von der Höden FJ, Stefansdottir SB, Torsteinsdottir S, Svansson V, Björnsson JM, Wagner B, Mahmuti D, Marti E, Jonsdottir S.Insect bite hypersensitivity (IBH) is a seasonal, IgE-mediated allergic dermatitis of horses caused by salivary gland proteins of biting midges ( spp.). Current management relies on relief of clinical signs and on physical protection. In a previous pilot study, healthy horses were fed transgenic barley expressing a allergen via a special spiral bit, which successfully induced allergen-specific antibody responses. Building on this concept, the present study aimed to evaluate a more practical feeding approach, delivering transgenic barley expressing the major allergen Cul o 2p in a feed-compat...
Beniwal N, Lal B, Mithina S, Verma CK, Kumar S, Phagna V, Jakhar K, Sonar S, Gupta V, Singh R, Kumar N, Tan CW, Thachamvally R, Singha H, Murzello K....Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission ...
Varela V, Costa M, Maciel C, Barbeito J, Barrera EE, Gutierre E, Correa A, Elgue M, Carrasco S, Larrosa MD, Pereira M, Correa J, Crosignani N....Anti-NGF monoclonal antibodies have recently been approved for treating degenerative joint disease, including osteoarthritis pain, in dogs and cats. However, their widespread use is limited by high cost and the requirement for repeated injections. Nerve Growth Factor and Substance P play central roles in the initiation and maintenance of inflammation and chronic pain in OA. There is a pressing need for new, safe, cost-effective therapies that target the underlying mechanisms of OA chronic pain. Here, we designed and produced a novel recombinant fusion protein, termed rNGFSP, which functions as...
Epizootic lymphangitis (EEL), caused by Histoplasma capsulatum var. farciminosum (HCF), is a neglected equine fungal disease lacking effective vaccines. The newly developed inactivated '8ZH' vaccine requires safety validation in the target species. Objective: To evaluate the biochemical, haematological and clinical safety of the inactivated HCF '8ZH' vaccine in foals. Methods: A controlled, single-blinded study was conducted on 30 clinically healthy foals (4-6 months), randomized into vaccinated (n = 15) and control (n = 15) groups. Vaccinated animals received a 5 mL intramuscular dose (...
Carey KJ, Smith I, Hartley CA, Bailey KE, McIntosh K, Broder CC, Gilkerson JR.Hendra virus (HeV) is a high consequence pathogen that causes severe respiratory and/or neurological disease in both horses and humans with high mortality. The equine vaccine, Equivac® HeV, is a recombinant soluble version of the G glycoprotein of HeV (HeV-sG) that elicits a potent HeV-neutralising antibody response in adult horses and also provides indirect protection for humans. Maternally derived HeV-G specific antibodies could interfere with subsequent foal vaccination, although other factors such as foal age and the suitability of vaccination protocols that have been optimised for adult ...
Whitlock F, Newton R, King S, Ionescu AM, Higgins S.With the geographical distribution of West Nile virus expanding, there is growing concern about the potential for an incursion to the UK. Here, Fleur Whitlock, Richard Newton, Simon King, Andra-Maria Ionescu and Sara Higgins provide a timely reminder of key aspects of the virus' biology.
Dong-Ha L, Eun-Bee L, Jong-Pil S, Eun-Ju K.Despite routine vaccination, equine influenza outbreaks occur due to disparities of virus strains between vaccine and field, and immunity gaps between vaccinations. Objective: To evaluate whether a combination of adjuvants can enhance immune responses to equine influenza virus (EIV) vaccines. Methods: In vivo experimental study. Methods: Eight mixed-breed horses were immunised intramuscularly with a recombinant canarypox-based EIV vaccine, either alone or in combination with monophosphoryl lipid A (MPL) and polyinosinic-polycytidylic acid (poly I:C). A single vaccine dose was administered, and...
Yang Y, Guo K, Xu L, Guo W, Dong M, Liu W, Li S, Zhang Z, Chu X, Wang Y, Zhang Z, Hu Z, Wang X.Equine influenza (EI), caused by the equine influenza virus (EIV), is an acute respiratory disease that has become enzootic worldwide, resulting in frequent outbreaks and substantial economic losses within the equine industry. In this study, we developed a competitive enzyme-linked immunosorbent assay (NP-cELISA) for the detection of antibodies against the EIV nucleoprotein (NP). The assay was designed by coating plates with purified monoclonal antibodies (mAbs) against the NP protein, followed by simultaneous incubation of the test serum samples and HRP-NP antigen in a competitive binding rea...
Jebbawi F, Olomski F, Inversini V, Keller G, Rhiner T, Waldern N, Lam J, Pantelyushin S, Canonica F, Birkmann K, Johansen P, Kündig TM....Skin allergies are among the most frequent types of allergies, where continuous investigation of the pathological immune mechanisms is required for a better understanding and a more effective treatment of the disease. In this study, we aimed to investigate the effect of interleukin (IL)-5 vaccination on allergen-specific IgE antibodies as well as T cell cytokine modulation in skin allergy using a mouse model and a naturally occurring disease in horses. Methods: Ovalbumin (OVA)-sensitized mice, as well as horses affected by equine insect bite hypersensitivity (IBH) were administered an anti-IL-...
Centers A, Barnaby K, Goedeker S, Pignataro A, Tretyakova I, Lukashevich I, Pushko P, Chung D.There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion and reversion, exhibited no neuroinvasion potential in a murine model. Following subcutaneous or intramuscular administration, a subset of mice that received the ...
Tinarwo M, Dennis SJ, Hitzeroth II, Meyers AE, Rybicki EP, Mbewana S.African horse sickness (AHS) is a severe, noncontagious disease of equines caused by the African horse sickness virus (AHSV). The virus has nine serotypes and is transmitted by the midge. AHS is endemic in South Africa and other sub-Saharan African countries. Currently, the disease is managed using a live attenuated vaccine manufactured by Onderstepoort Biological Products (OBP). Although this vaccine has been in use for decades, it has several drawbacks, including the possibility of reversion to virulence, and it does not allow for the differentiation of infected horses from vaccinated horse...
Roncaglia-Pereira VA, Dumard CH, Monteiro-Machado M, Melo PA, Fonseca J, Meirelles L, Cunha-Ribeiro L, Souza P, da Silva JL, Castilho L....In this study, we aim to report the persistent presence of anti-SARS-CoV-2 immunoglobulins in pre-immunized mare offspring. Three mares from Vital Brazil Institute were pre-immunized with recombinant SARS-CoV-2 spike protein and became pregnant during this period. After parturition, the mares' serum and colostrum/milk and foal serum were collected over 6 weeks. Our results have shown high and persistent presence of IgG and neutralizing antibodies over the weeks not only in the mares' serum, as expected, but in mares' colostrum/milk and foal serum as well-what were very surprising. This peculia...
Batterham R, Allen K, Dickson J, Warman S, Parkin T.To ensure veterinary students are prepared for clinical practice, curricula must provide opportunities for students to learn about the cases most frequently seen in practice. Currently, there is a gap in the literature with regard to the identification of common clinical topics encountered in equine primary care practice in the UK. This study aims to address this gap by utilizing text-mining techniques on electronic medical records (EMRs) to produce a ranked list of the most common clinical topics encountered in equine primary care in the UK. The study included 1,092,731 rows of data from 150,...
Whitlock F, McGlennon A, Newton R, Riley K.As part of her undergraduate research project, Cambridge vet student Katie Riley surveyed the attitudes of UK veterinarians with regard to preventing and controlling strangles, including the use of vaccination. Here, she and Fleur Whitlock, Abigail McGlennon and Richard Newton of Equine Infectious Disease Surveillance discuss her findings.
Legere RM, Ott JA, Poveda C, Vanover D, Borba KER, Yeon Joo J, Martin CL, da Silveira BP, Bray JM, Landrock K, Wright GA, Blazier JC, Hillhouse AE....Inhalation of Rhodococcus equi causes severe pneumonia in humans and animals worldwide, most commonly affecting horse foals. The standard for preventing R. equi pneumonia in foals is transfusion of hyperimmune plasma, which is expensive and carries the risk of adverse effects. Our goal was to passively immunize foals against R. equi by nebulizing mRNA encoding an equine monoclonal antibody (mAb) against the virulence-associated protein A (VapA) directly into the lungs. VapA-specific memory B cells from an immunized horse were used to identify and select the sequence for an equine immunoglobuli...
Bannai H, Kambayashi Y, Kume K, Takebe N, Endo Y, Kawanishi N, Nemoto M, Tsujimura K.The endemic situation of respiratory disease caused by equine herpesvirus type-1 (EHV-1) and type-4 (EHV-4) was investigated in a training facility for Thoroughbred yearlings in Japan. Vaccination typically starts in mid-September or early October-only after all yearlings have arrived-leaving those introduced earlier unprotected. To bridge this immunity gap, a revised vaccination program that started earlier was implemented. In 2021-2022 and 2022-2023, yearlings were allocated to three groups according to their introduction dates. Each group received a live EHV-1 vaccine (Equi N Tect ERP, Niss...
Kutumbetov L, Myrzakhmetova B, Tussipova A, Zhapparova G, Tlenchiyeva T, Bissenbayeva K, Nurabayev S, Kerimbayev A.Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent vaccine for EHV-4, and existing formulations offer limited protection against this serotype. This study aimed to develop and evaluate a freeze-dried, live-attenuated EHV-4 vaccine with improved safety, stability, and immunogenicity. Methods: A field isolate of EHV-4 was attenuated through serial passaging in ...
da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI.Using a horse foal model, we show that enteral immunization of newborn foals with Rhodococcus equi overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of R. equi (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with R. equi. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foa...
Golen GS, Erganiş O, Balevi A. is an important bacterial pathogen and causes severe chronic granulomatous pneumonia in foals below 6 months of age. It has also become an opportunistic and emerging pathogen in immunocompromised humans. Vaccination is the most cost-effective strategy for controlling and preventing this infection. Although several potential virulence genes and candidate immunogens have been identified over the years, no effective vaccine is currently available to prevent disease in horses. Recently, bacterial vector vaccines have been shown to be promising for In this study, the gene of was cloned into P...
Matté YA, Baldasso DZ, Rezende MA, Lui JFM, Seibel AC, Guizzo JA, Frandoloso R, Kreutz LC.Lawsonia intracellularis is an obligatory intracellular bacterium associated with equine proliferative enteropathy (EPE), which significantly impacts equine health. Despite its clinical relevance, epidemiological and diagnostic approaches for this infection in horses have remained underexplored. This study aimed to evaluate the humoral immune response in horses immunized with an experimental vaccine for L. intracellularis and to determine the occurrence of anti-L. intracellularis antibodies in horses from southern Brazil using the flow cytometry antibody test (FCAT). Unassigned: A total of 12 ...
Levasseur A, Paré J, Aubry P, Iwasawa S, Leung D, Arsenault J.Vaccination is the most efficient tool for preventing West Nile virus (WNV) disease in horses. The objectives of this retrospective study were to: i) estimate the provincial and national horse population in Canada; ii) estimate the annual vaccination coverage for WNV in each province; and iii) compare estimates of provincial annual vaccination coverage. Horse population data (2006-2023) and the number of vaccine doses sold in Canada (2016-2020) were obtained by province. Based on these data and expert consultations, the annual number of vaccine doses administered, and provincial horse populati...
Rykala M, Jasiak M, Niedzwiedz A.Preventing the spread of infectious diseases in horses requires breaking the chain of infection through appropriate prophylaxis. In Poland, where the horse population reached 273,006 in 2023, vaccinations are voluntary and primarily the responsibility of horse owners, with mandatory influenza vaccinations limited to sport horses. This study aimed to evaluate the vaccination status of Polish horses against infectious diseases through a survey of 980 horse owners and an analysis of 123 horse passports from slaughterhouses. Survey participants represented all provinces, predominantly owning warmb...
Wagner B, Schnabel CL, Rollins A.Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vacc...
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...
Davis BS, Chang GJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML.Introduction of West Nile (WN) virus into the United States in 1999 created major human and animal health concerns. Currently, no human or veterinary vaccine is available to prevent WN viral infection, and mosquito control is the only practical strategy to combat the spread of disease. Starting with a previously designed eukaryotic expression vector, we constructed a recombinant plasmid (pCBWN) that expressed the WN virus prM and E proteins. A single intramuscular injection of pCBWN DNA induced protective immunity, preventing WN virus infection in mice and horses. Recombinant plasmid-transform...
Pallister J, Middleton D, Wang LF, Klein R, Haining J, Robinson R, Yamada M, White J, Payne J, Feng YR, Chan YP, Broder CC.The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirror...
Palaniappan RU, Chang YF, Jusuf SS, Artiushin S, Timoney JF, McDonough SP, Barr SC, Divers TJ, Simpson KW, McDonough PL, Mohammed HO.A clone expressing a novel immunoreactive leptospiral immunoglobulin-like protein A of 130 kDa (LigA) from Leptospira interrogans serovar pomona type kennewicki was isolated by screening a genomic DNA library with serum from a mare that had recently aborted due to leptospiral infection. LigA is encoded by an open reading frame of 3,675 bp, and the deduced amino acid sequence consists of a series of 90-amino-acid tandem repeats. A search of the NCBI database found that homology of the LigA repeat region was limited to an immunoglobulin-like domain of the bacterial intimin binding protein of Esc...
Levy R, Forsyth CM, LaPorte SL, Geren IN, Smith LA, Marks JD.Botulinum neurotoxin (BoNT), the most poisonous substance known, causes naturally occurring human disease (botulism) and is one of the top six biothreat agents. Botulism is treated with polyclonal antibodies produced in horses that are associated with a high incidence of systemic reactions. Human monoclonal antibodies (mAbs) are under development as a safer therapy. Identifying neutralizing epitopes on BoNTs is an important step in generating neutralizing mAbs, and has implications for vaccine development. Here, we show that the three domains of BoNT serotype A (BoNT/A) can be displayed on the...
Ng T, Hathaway D, Jennings N, Champ D, Chiang YW, Chu HJ.To meet the urgent need of controlling West Nile virus (WNV) infection in the equine population, we have developed a killed WNV vaccine. A dose titration study in horses was first conducted to evaluate serum neutralization antibody responses against WNV in these animals. Horses were vaccinated intramuscularly twice with the test vaccine at low, medium and high dose, three weeks apart. Serum samples were collected periodically and were measured for serum neutralizing antibody using a plaque reduction neutralization test. Significant increases in serum neutralizing antibody were detected in all ...
Lobigs M, Pavy M, Hall RA, Lobigs P, Cooper P, Komiya T, Toriniwa H, Petrovsky N.Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a ...
Thompson JM, Whitmore AC, Konopka JL, Collier ML, Richmond EM, Davis NL, Staats HF, Johnston RE.Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon pa...
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...
Angenvoort J, Brault AC, Bowen RA, Groschup MH.West Nile virus (WNV) is a flavivirus transmitted between certain species of birds and mosquito vectors. Tangential infections of equids and subsequent equine epizootics have occurred historically. Although the attack rate has been estimated to be below 10%, mortality rates can approach 50% in horses that present clinical disease. Symptoms are most commonly presenting in the form of encephalitis with ataxia as well as limb weakness, recumbency and muscle fasciculation. The most effective strategy for prevention of equine disease is proper vaccination with one of the numerous commercially avail...
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...
Goodman LB, Wagner B, Flaminio MJ, Sussman KH, Metzger SM, Holland R, Osterrieder N.Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus of horses which causes rhinopneumonitis, abortion and myeloencephalopathy. To test the efficacy of commercial vaccines in protection against neurological EHV-1 challenge, groups of five horses were immunized with modified-live virus or an inactivated vaccine, or received placebo. Horses were challenged by aerosol with a recent virus isolate obtained from a case of paralytic EHV-1. The duration of fever decreased significantly in the modified-live virus vaccine group. Three animals in each of the inactivate and control groups sh...
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...
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...
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...
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-...
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...
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...
Reed DS, Glass PJ, Bakken RR, Barth JF, Lind CM, da Silva L, Hart MK, Rayner J, Alterson K, Custer M, Dudek J, Owens G, Kamrud KI, Parker MD, Smith J.Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon v...
Nally JE, Artiushin S, Timoney JF.Leptospira interrogans is a mammalian pathogen which must adapt to a range of new environmental conditions including temperature change when it infects new hosts. In vitro studies of organisms cultured at 30 degrees C and shifted to 37 degrees C for 5 to 7 days have confirmed that synthesis of several proteins involved in equine infection is regulated in response to temperature change (J. E. Nally, J. F. Timoney, and B. Stevenson, Infect. Immun. 69:400-404, 2001). In order to specifically identify antigenic proteins upregulated at 37 degrees C, groups of three ponies were immunized with organi...
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...
Smith T.The foregoing and earlier data taken together demonstrate that an active immunity lasting several years can be produced in guinea-pigs, by the injection of toxin-antitoxin mixtures which have no recognizable harmful effect either immediate or remote. They also show, what might have been anticipated, that under the same conditions mixtures which produce local lesions and which, therefore, contain an excess of toxin produce a much higher degree of immunity than the neutral mixtures, and that an excess of antitoxin reduces the possibility of producing an active immunity, and may extinguish it alt...
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...
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...
Morein B, Blomqvist G, Hu K.The maintenance of pregnancy requires suppression of the maternal immune system which would naturally recognize the developing fetus as an allograft and seek to destroy it by mounting a Th1 regulated cytotoxic immune response. During pregnancy a range of soluble factors are produced by the placenta which switch maternal immune regulation towards a protective Th2 phenotype. These factors also influence the developing fetal immune system and all newborns initially have an immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal period must therefore overcome the dual cha...
Balasuriya UB, Heidner HW, Davis NL, Wagner HM, Hullinger PJ, Hedges JF, Williams JC, Johnston RE, David Wilson W, Liu IK, James MacLachlan N.Replicon particles derived from a vaccine strain of Venezuelan equine encephalitis (VEE) virus were used as vectors for expression in vivo of the major envelope proteins (G(L) and M) of equine arteritis virus (EAV), both individually and in heterodimer form (G(L)/M). The immunogenicity of the different replicons was evaluated in horses, as was their ability to protectively immunize horses against intranasal and intrauterine challenge with a virulent strain of EAV (EAV KY84). Horses immunized with replicons that express both the G(L) and M proteins in heterodimer form developed neutralizing ant...
Alberca B, Bachanek-Bankowska K, Cabana M, Calvo-Pinilla E, Viaplana E, Frost L, Gubbins S, Urniza A, Mertens P, Castillo-Olivares J.African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR -/-) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice wit...
