Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease.
The control of EHV-1 infection by cytotoxic T-cell responses (CTL) via a reduction in cell associated viremia remains an important goal in horses. Unfortunately, current vaccines are inefficient at inducing these responses. We have identified the immediate early (IE) gene of EHV-1 as a potent stimulator of virus-specific CTL responses in ponies expressing a specific MHC class I serological haplotype (A3/B2). This study was designed to determine if vaccination of A3/B2 MHC I positive ponies with the IE gene could induce protection and immune responses associated with cell mediated immunity. Ponies expressing the MHC-I A3/B2 haplotype (A3/B2 vaccinates) and ponies with a different MHC I haplotype (either non-A3 vaccinates or A3-non-B2 vaccinates) were vaccinated with a recombinant modified vaccinia Ankara (rMVA) vector expressing the IE gene on 3 occasions and vaccinates and unvaccinated controls were challenge infected 8 weeks after the last vaccination. Interferon gamma (IFN-gamma) mRNA and antibody titers were determined throughout the study and clinical signs, nasal virus shedding and viremia were determined following challenge infection. Vaccination of A3/B2 vaccinates conferred significant clinical protection and a significant reduction in EHV-1 viremia. IFN-gamma mRNA increased significantly following vaccination in the A3/B2 vaccinates. Antibody titers remained low until after challenge infection, indicating that no accidental field acquired or recrudescent EHV-1 infection had occurred. In summary, this is an important study showing that vaccination of ponies with the EHV-1 IE protein provides not only reduction in clinical disease but also reduction of cell associated viremia, which is a prerequisite for the prevention of abortion and neurological disease.
Soboll
G
G
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA.
Breathnach
C C
CC
Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40546, USA.
Kydd
J H
JH
School of Veterinary Medicine and Science, University of Nottingham, Loughborough, Leicestershire LE12 5RD, UK.
Hussey
S B
SB
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA.
Mealey
R M
RM
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Lunn
D P
DP
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA. Electronic address: lunnp@mail.colostate.edu.
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D005260:Female; D017781:Genes, Immediate-Early / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006734:Horse Diseases / Q000276:immunology / Q000517:prevention & control*; D006736:Horses / Q000276:immunology / Q000821:virology; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014615:Vaccinia; D014766:Viremia / Q000276:immunology / Q000662:veterinary
D057134:Antibodies, Neutralizing; D022283:Herpesvirus Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma