Topic:Vaccine development
Vaccine development in horses involves the creation and refinement of immunizations to protect equine populations from infectious diseases. This process includes identifying antigens, formulating vaccines, and evaluating their safety and efficacy through clinical trials. Vaccines stimulate the horse's immune system to recognize and combat specific pathogens, thereby reducing the incidence and severity of diseases. Common equine vaccines target diseases such as equine influenza, tetanus, and West Nile virus. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, challenges, and advancements in vaccine development for equine health.
Diagnosis and prevention of equine infectious diseases: present status, potential, and challenges for the future. The frequent transfers of horses, whether on a permanent or temporary basis, make strict control of infectious diseases essential. Such control needs a reliable and rapid means to accurately diagnose the relevant diseases. Indirect diagnosis based on antibody detection remains certainly the best method to secure the epidemiologic surveillance of the diseases at regional, national, or even world level, while direct diagnosis is the only way to diagnose a new outbreak. New diagnostic methods resulting from advances in biochemistry, molecular biology, and immunology are now available. As far as a...
Suppressant effect of human or equine rabies immunoglobulins on the immunogenicity of post-exposure rabies vaccination under the 2-1-1 regimen: a field trial in Indonesia. MAS054 Clinical Investigator Group. WHO's reference protocol for post-exposure rabies vaccination advises five intramuscular injections on days 0, 3, 7, 14, and 30; in addition, rabies immunoglobulins (RIG) must be given to serious cases of exposure (grade III severity). Some studies indicate that these immunoglobulins suppress the immunogenicity of rabies vaccine when administered according to an alternative protocol of four injections (2-1-1) on days 0, 7, and 21, which was therefore not recommended for grade III exposures. To test this effect, we conducted a multicentre study in Indonesia using three groups of subjects. One g...
Future international management of African horse sickness vaccines. Three types of African horse sickness (AHS) vaccine, namely adult mouse brain, modified live vaccine and inactivated viral vaccine (IVV) are reviewed. The results of efficacy trials carried out with each vaccine type highlight the advantages of the IVV. Vaccination with African horse sickness virus serotype 4 IVV, given as 2 separate doses, provided full protection against subsequent, homologous challenge. The absence of any detectable viraemia after challenge would also prevent infection of insect vectors. The advantages of establishing international vaccine banks for AHS are discussed.
Western immunoblotting as a method for the detection of African horse sickness virus protein-specific antibodies: differentiation between infected and vaccinated horses. A Western immunoblotting procedure has been developed for the detection of African horse sickness virus (AHSV) protein-specific antibody responses. This assay readily identifies antibodies specific for at least 4 distinct, AHSV proteins, including VP5, NS1, NS2 and NS3/NS3a. By using the AHSV non-structural proteins as 'markers', the Western blotting procedure could be employed to provide a reliable means of discriminating between animals vaccinated with a purified, inactivated AHSV vaccine and those either naturally infected or vaccinated with a live, attenuated AHSV vaccine.
Local and systemic isotype-specific antibody responses to equine influenza virus infection versus conventional vaccination. Inactivated alum-adjuvanted conventional equine influenza virus vaccines are of poor efficacy and offer limited short-term protection against infection. In sharp contrast, natural infection with equine influenza virus confers long-term protective immunity. In order to identify the protective immune responses to equine influenza virus, the influenza virus-specific IgA, IgGa, IgGb, IgGc and IgG(T) antibody responses in nasal secretions and serum induced by natural infection and a commercial vaccine were studied by ELISA. Two groups of four influenza-naive ponies were established. In the natural ...
Molecular basis for antigenic variation of a protective strain-specific antigen of Ehrlichia risticii. Ehrlichia risticii, the causative agent of Potomac horse fever, has recently been isolated from many vaccinated horses with typical clinical signs of the disease. The heterogeneity of the E. risticii isolates obtained from the vaccinated horses necessitates the identification of the molecular basis of strain variations to elucidate the vaccine failure and to aid in the development of an efficient vaccine against this disease. As an attempt, two major cross-reacting surface antigen genes of 50- and 85-kDa antigens, present separately in strains 25-D (isolated in 1984) and 90-12 (isolated in 199...
Direct sequencing of the HA gene of clinical equine H3N8 influenza virus and comparison with laboratory derived viruses. Equine influenza viruses propagated in the laboratory in alternate hosts such as embryonated hens' eggs or mammalian cell culture have been analysed by HA sequencing and antigenically and their sequence compared to the original virus present in clinical material. In contrast to clinically derived human influenza virus which generally grows in MDCK cells without change, the data for equine influenza virus were less clear in that variants of equine virus were derived in both eggs and cells. The study indicated that the current use of eggs for equine influenza virus surveillance and vaccine produ...
Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement. We have previously reported that immunization of ponies with a baculovirus-expressed recombinant surface unit envelope protein (rgp90) for equine infectious anemia virus (EIAV) resulted in enhancement of disease symptoms and virus replication in 4 of 4 vaccine recipients subjected to a heterologous virus challenge (rpg90 I vaccine trial) (Wang et al., 1994). To extend these studies of EIAV vaccine enhancement, two additional and independent rgp90 vaccine trials (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were immunized with the rgp90 immunogen using our standard vac...
Affinity purification and characterization of a fibrinogen-binding protein complex which protects mice against lethal challenge with Streptococcus equi subsp. equi. Cell-wall-associated proteins from Streptococcus equi subsp. equi, the causative agent of strangles, were analysed with a view to identifying a potential protective antigen. Preparations of these proteins, isolated from mutanolysin extracts of cell walls, were shown to contain one major high-M(r) protein species (apparent M(r) 220,000 and 550,000 when analysed by SDS-PAGE and gel-filtration chromatography, respectively). The high-M(r) protein bound horse fibrinogen and was purified under non-denaturing conditions using fibrinogen affinity chromatography. The fibrinogen-binding protein (FgBP) r...
Evidence that surface proteins Sn14 and Sn16 of Sarcocystis neurona merozoites are involved in infection and immunity. Sarcocystis neurona is the etiologic agent of equine protozoal myeloencephalitis (EPM). Based on an analysis of 25,000 equine serum and cerebrospinal fluid (CSF) samples, including samples from horses with neurologic signs typical of EPM or with histologically or parasitologically confirmed EPM, four major immunoblot band patterns have been identified. Twenty-three serum and CSF samples representing each of the four immunoblot patterns were selected from 220 samples from horses with neurologic signs resembling EPM and examined for inhibitory effects on the infectivity of S. neurona by an in vi...
In vitro propagation of Theileria annulata infected schizonts in different media supplemented with heterologous sera. Efficacy of medium RPMI-1640 (supplied by Gibco USA, Centron and Hi-media) supplemented with horse, donkey, sheep and goat sera was evaluated for in vitro propagation of Theileria annulata (Hisar) infected bovine mononuclear cells. The results were compared with the growth rate in RPMI-1640 supplemented with foetal bovine serum (Gibco). RPMI-1640 (Gibco) proved to be the best medium for in vitro cultivation of the parasite infected cells. Foetal bovine serum could be easily, safely and reliably substituted with goat and sheep sera in the growth medium. Horse and donkey sera also gave comparabl...
Nucleotide sequences of glycoprotein I and E genes of equine herpesvirus type 4. The nucleotide sequences of the glycoprotein I (gI) and E (gE) genes of equine herpesvirus type 4 (EHV-4) strain TH20 were determined. The predicted region encoding the EHV-4 gI gene is 1,263 nucleotides, corresponding to a polypeptide of 420 amino acids in length. The predicted region encoding the EHV-4 gE gene is 1,647 nucleotides, corresponding to a polypeptide of 548 amino acids in length. The EHV-4 gI and gE genes show 74% and 85% identity at the amino acid level with those of equine herpesvirus type 1 (EHV-1), respectively. Furthermore, we have found an open reading frame homologous to t...
Venereal infection of mares by equine arteritis virus and use of killed vaccine against the infection. Venereal infection with equine arteritis virus (EAV) was established in each of seven mares by inoculation via the cervix with 20 ml of viral suspension (> or = 8 x 10(6) plaque-forming units; PFU), following treatment with prostaglandin and oestradiol. A dose of < or = 8 x 10(5) PFU produced infection in only five of eight mares. Serum neutralizing antibody developed in mares manifesting clinical signs of equine viral arteritis (EVA), and a weak antibody was detectable in one apparently healthy mare inoculated with 8 x 10(5) PFU. Virus isolation was demonstrated not only in the buffy coat but...
Expression cloning and humoral immune response to the nucleocapsid and membrane proteins of equine arteritis virus. To provide a convenient and sensitive method for the detection of equine arteritis virus (EAV)-specific serum antibodies, we developed an immunoblot assay employing the EAV nucleocapsid (N) and membrane (M) proteins expressed in a procaryotic expression vector (pMAL-c2) for the production of recombinant maltose-binding (MBP) fusion proteins (MBP-N and MBP-M). The antigenic reactivity of the recombinant fusion proteins and their Xa factor cleavage EAV products was confirmed by immunoblot using horse antisera to EAV. Some horse sera, however, showed immune reactivity to the MBP fusion partner pr...
Preliminary study of ovarian activity in fillies treated with a GnRH vaccine. To investigate the effects of two doses (200 and 400 mg) of a water-soluble gonadotrophin-releasing hormone vaccine on the ovarian activity of 2-year-old fillies. Methods: A controlled vaccination dose rate experiment. Methods: Six 2-year-old Australian Stock Horse fillies were randomly allocated to three treatment groups; unvaccinated controls, those receiving 200 mg of the vaccine and those receiving 400 mg of the vaccine. Results: Ovarian activity of the treated fillies was suppressed at the peak of breeding season while that of untreated controls continued normally. The control fillies dis...
Production of highly potent horse antivenom against the Thai cobra (Naja kaouthia). Naja kaouthia (NK) causes the highest fatality due to snake venom poisoning in Thailand. The specific antivenom produced is of low potency and in short supply. The aim of this study was to improve the antivenom potency. Bentonite and complete Freund's adjuvants (CFA) and various immunogens were compared. Six groups of three to five horses were immunized as follows: Group 1, NK venom adsorbed on bentonite; Group 2, NK venom in CFA; Group 3, NK venom in CFA in multi-emulsion formulation; Group 4, NK venom in 25% CFA; Group 5, NK neurotoxin 3 (NK3) conjugated with tetanus toxoid (NK3-TT) in CFA; ...
Field study of the safety, immunogenicity, and efficacy of an inactivated equine rotavirus vaccine. To determine safety, immunogenicity, and efficacy of an inactivated equine rotavirus vaccine. Methods: Prospective randomized controlled trial. Methods: 316 pregnant Thoroughbred mares during the first year of the study and 311 during the second year. Methods: During the first year, mares received 3 doses of vaccine or placebo, IM, at 8, 9, and 10 months of gestation. Serum neutralizing antibody titers were measured before vaccination and 1 and 35 days after foaling. Antibody titers were measured in foals 1, 7, 35, 60, 90, and 120 days after birth. During the second year, mares that had been v...
Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine influenza virus hemagglutinin vaccines in mice. Two fundamentally different approaches to vaccination of BALB/c mice with the hemagglutinin (HA) of A/Equine/Kentucky/1/81 (H3N8) (Eq/KY) were evaluated, that is, administration of HA protein vs administration of HA-encoding DNA. Each vaccine was tested for its immunogenicity and ability to provide protection from homologous virus challenge. HA protein was synthesized in vitro by infection of Sf21 insect cells with a recombinant baculovirus. Intranasal administration of this vaccine induced virus-specific antibodies, as measured by enzyme-linked immunosorbent assay (ELISA), but did not induce ...
Antigenic analysis of Rhodococcus equi preparations using different horse sera. An R. equi vaccine, prepared under conditions which induce the expression of many antigens, and which has given encouraging results in field trials, was analyzed by SDS-PAGE and immunoblots and compared with other R. equi preparations: a preparation made in with the same technique from a nonvirulent isolate (virulence associated protein negative, VapA-negative); a whole cell preparation of a VapA-positive R. equi, prepared as a standard bacterin; and a semipurified VapA preparation (APTX). The antigens in these preparations were analyzed using hyperimmune sera (from adult horses vaccinated wit...
Protective effect against Rhodococcus equi infection in mice of IgG purified from horses vaccinated with virulence associated protein (VapA)-enriched antigens. IgG was purified from horses immunized with repeated doses of virulence associated (VapA) enriched antigens extracted with Triton X-114 from the surface of a virulent strain of R. equi. This IgG were administered to mice immunosuppressed by prior treatment with indomethacin. Mice administered the higher dose were completely protected against intraperitoneal infection with R. equi; mice given the lower dose were partially protected. By contrast, mice administered concentrated nonimmune equine IgG were not protected. This study demonstrates that VapA may be an important antigen involved in humor...
Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been...
Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse. Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succ...
Simulation studies of vaccination strategies in African horse sickness. A simulation model including two hosts (horses and donkeys) and one vector (Culicoides imicola) for African horse sickness in Spain is extended to consider vaccination strategies. If hosts were protected prior to virus introduction, elimination of simulated epidemics was related nonlinearly to the fraction protected. Protecting donkeys as well as horses increased the effectiveness of vaccination. Prevention of 50% of epidemics required 75% coverage of horses and donkeys or 90% coverage of horses only. Protection after the introduction of the virus was rarely successful in preventing outbreaks....
Use of Rhodococcus equi virulence-associated protein for immunization of foals against R equi pneumonia. To evaluate use of the virulence-associated protein of Rhodococcus equi in immunizing foals against R equi pneumonia. Methods: Eight (experimental group) and 6 (controls) mares with their foals. Methods: Virulence-associated protein extracted from R equi was used to prepare an acetone-precipitated. Triton X-extracted (APTX) antigen. After determination of the efficacy of passive immunization, in untreated foals or in foals given plasma from a horse vaccinated with APTX antigen or from a nonvaccinated horse, a field trial was done to evaluate the efficacy of vaccination of 8 mares, twice with A...
Case studies in wildlife immunocontraception: wild and feral equids and white-tailed deer. Non-lethal management methods are required for wild equids that are protected by law and for deer inhabiting areas where lethal controls are not legal or safe. Single or multiple inoculations of porcine zona pellucida (PZP) vaccine have been delivered to wild horses and deer by means of darts. Contraceptive efficacy in horses after two inoculations ranged from 90% to 100%, and after a single inoculation ranged from 19% to 28%. Mares given a controlled-release form of the vaccine had foaling rates ranging from 7% to 20%. No detectable changes in social organization or behaviours among treated h...
Mutational changes in the hemagglutinin of equine H3 influenza viruses result in the introduction of a glycosylation site which enhances the infectivity of the viruses. The complete amino acid sequences of the hemagglutinin (HA) glycoprotein of three equine-2 influenza viruses from tropical Africa are presented in comparison with that of a well characterized European equine-2 virus (Suffolk/89) and a consensus sequence from the database. The sequences of the tropical African viruses were deduced from the complete nucleotide sequences of their HA genes reported earlier. Mutational changes in the nucleotide sequences resulted in amino acid changes in the HA which led to the introduction of a new asparagine-linked (N-linked) glycosylation site in two viruses. Th...
Recombinant baculovirus-synthesized African horsesickness virus (AHSV) outer-capsid protein VP2 provides protection against virulent AHSV challenge. African horsesickness virus serotype 4 (AHSV-4) outer-capsid proteins VP2 or VP2 and VP5, prepared from single or dual recombinant baculovirus expression vectors grown in Sf9 insect cells, were administered in different amounts to horses and the neutralizing antibody responses were measured. Control and vaccinated horses were challenged with virulent AHSV-4 6 months later and monitored post challenge. The results indicated that two inoculations of extracts containing VP2 and VP5, or VP2 alone, in doses of 5 micrograms VP2 or more per horse, were sufficient to elicit protection against African ...
Suppression of testicular function using two dose rates of a reversible water soluble gonadotrophin releasing hormone (GnRH) vaccine in colts. To investigate the effect of two dose rates (200 and 400 ng) of a gonadotrophin releasing hormone (GnRH) vaccine on testicular function. Methods: A vaccination dose rate experiment. Methods: Two injections were administered 4 weeks apart to six colts in each treatment group. To maintain immunosuppression until the end of the breeding season, a third injection was given if antibody titres fell below 1000. Results: Effective antibody titres were present for 12 to 27 weeks. Testosterone concentrations decreased from 2.22 to 0.31 nmol/L 6 weeks after primary vaccination. Androstenedione concentrat...
Heterologous antisera and antivenins are essential biologicals: perspectives on a worldwide crisis. Active immunization against infectious disease is important. However, much of our world faces poverty, social injustice, and warfare, all of which cause universal immunization to remain a distant dream. Agents that provide passive immunity thus remain essential biologicals. The most important of these are human or equine antisera against rabies, tetanus, diphtheria, and snake antivenins. Homologous products are either unavailable or unaffordable in places where they are needed the most. Less expensive heterologous (equine) antisera can be purified and are safe to use, but these antisera are al...