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

Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leadin g candidates in efficacy trials conducted in both animal models and humans. To date, lentivirus vaccination strategies have overlooked one such immuni zation strategy, namely the use of particulate antigens. To evaluate the ef ficacy of targeting antigen into the phagocytic pathway to elicit a cell-me diated immune response to lentiviral antigens, we initiated the first study of a particulate-based vaccination protocol using a large animal model sys tem. Gradient-purified equine infectious anemia virus (EIAV) was covalently coupled to glutaraldehyde-activated iron oxide beads. in vitro studies dem onstrated the effectiveness of the inactivated whole virus particulate to p rime antigen presenting cells for the activation and expansion of virus-spe cific CD8(+) CTL. The in vivo effectiveness of the particulate antigen was evaluated by experimental immunization of ponies. Ponies receiving the vira l particulate vaccine and challenged with infectious EIAV had a delayed pro gression to disease and a reduced viral load compared with infected ponies that had not been vaccinated. Interestingly, in vitro virus-specific CTL ac tivity was detected in only one of four immunized animals at the day of cha llenge. The beneficial effects of the particulate vaccine regimen were not clearly associated with any in vitro measurable parameters of the virus-spe cific cellular or humoral immune responses elicited by the vaccine at the d ay of challenge. However, within 3 weeks after virus challenge, anamnestic humoral responses characterized by a rapid emergence of neutralizing activi ty in the serum and a predominance of conformationally dependent epitopes r ecognized by virus-specific antibodies were observed in the vaccinates. Tak en together, further studies are clearly warranted in large animal model sy stems using a particulate-based vaccine regimen considering the beneficial effects of this regimen in our study and the protective effects of particul ate antigen delivery in the murine model. (C) 1999 Academic Press.