A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus

Abstract

Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal models and humans. To date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. To evaluate the efficacy of targeting antigen into the phagocytic pathway to elicit a cell-mediated immune response to lentiviral antigens, we initiated the first study of a particulate-based vaccination protocol using a large animal model system. Gradient-purified equine infectious anemia virus (EIAV) was covalently coupled to glutaraldehyde-activated iron oxide beads. In vitro studies demonstrated the effectiveness of the inactivated whole virus particulate to prime antigen presenting cells for the activation and expansion of virus-specific CD8+ CTL. The in vivo effectiveness of the particulate antigen was evaluated by experimental immunization of ponies. Ponies receiving the viral particulate vaccine and challenged with infectious EIAV had a delayed progression to disease and a reduced vital Icad compared with infected ponies that had not been vaccinated. Interestingly, in vitro virus-specific CTL activity was detected in only one of four immunized animals at the day of challenge. The beneficial effects of the particulate vaccine regimen were not clearly associated with any in vitro measurable parameters of the virus-specific cellular or humoral immune responses elicited by the vaccine at the day of challenge. However, within 3 weeks after virus challenge, anamnestic humoral responses characterized by a rapid emergence of neutralizing activity in the serum and a predominance of conformationally dependent epitopes recognized by virus-specific antibodies were observed in the vaccinates. Taken together, further studies are clearly warranted in large animal model systems using a particulate-based vaccine regimen considering the beneficial effects of this regimen in our study and the protective effects of particulate antigen delivery in the murine model.