Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.
Improving the ability of DNA-based vaccines to induce potent Type1/Th1 responses against intracellular pathogens in large outbred species is essential. Rhodoccocus equi and equine infectious anemia virus (EIAV) are two naturally occurring equine pathogens that also serve as important large animal models of neonatal immunity and lentiviral immune control. Neonates present a unique challenge for immunization due to their diminished immunologic capabilities and apparent Th2 bias. In an effort to augment R. equi- and EIAV-specific Th1 responses induced by DNA vaccination, we hypothesized that a dual promoter plasmid encoding recombinant equine IL-12 (rEqIL-12) would function as a molecular adjuvant. In adult horses, DNA vaccines induced R. equi- and EIAV-specific antibody and lymphoproliferative responses, and EIAV-specific CTL and tetramer-positive CD8+ T lymphocytes. These responses were not enhanced by the rEqIL-12 plasmid. In neonatal foals, DNA immunization induced EIAV-specific antibody and lymphoproliferative responses, but not CTL. The R. equi vapA vaccine was poorly immunogenic in foals even when co-administered with the IL-12 plasmid. It was concluded that DNA immunization was capable of inducing Th1 responses in horses; dose and route were significant variables, but rEqIL-12 was not an effective molecular adjuvant. Additional work is needed to optimize DNA vaccine-induced Th1 responses in horses, especially in neonates.
Mealey
R H
RH
Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, Pullman, WA 99164-7040, USA.
Stone
D M
DM
Hines
M T
MT
Alperin
D C
DC
Littke
M H
MH
Leib
S R
SR
Leach
S E
SE
Hines
S A
SA
D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004333:Drug Administration Routes; D004797:Enzyme-Linked Immunosorbent Assay; D006736:Horses; D007115:Immunization Schedule; D004860:Infectious Anemia Virus, Equine / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins / Q000276:immunology; D016929:Rhodococcus equi / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000914:Antibodies, Viral; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D018664:Interleukin-12