ADARC PROGRAM PROJECT SIV & HIV VACCINE DEVELOPMENT

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We previously demonstrated that rhesus monkeys develop enhanced pulmonary histopathology after vaccination with a formalin inactivated (FI) preparation of respiratory syncytial virus (FI-RSV) and challenge with live RSV. These results were similar to those that followed natural infection in a group of FI-RSV vaccinated children in the 1960's. These adverse effects are believed to be immunologically based but the mechanism is unknown. We conducted a large RSV vaccine study using a Praxis Biologics preparation of formalin-inactivated RSV vaccine. Twenty seronegative rhesus macaques were divided into four groups of five animals each. Two groups received IM injections of FI-RSV vaccine preparation, either high dose or low dose. A third group received placebo vaccine and the fourth group was intranasally infected with live RSV. The infection group was followed through the initial course of infection for height and duration of infection as well as antibody response. A booster vaccination was given to groups 1-3 on day 21. Finally, a live RSV challenge was administered to all animals on day 56. The animals were monitored for the dynamics of their infection and then were humanely euthanized to assess pulmonary pathology on day 8 following viral challenge. The high dose vaccine group had the greatest antibody response to vaccine and the anticipated the lowest level of virus in the upper respiratory tract as compared with the the low dose vaccine group that had no antibody response and high titers of virus in the upper respiratory tract. These virus titers in this low vaccine group were also one to two logs lower that that demonstrated in the placebo control group. These results indicated a dose effect of the vaccine in these animals. As expected, the fourth reinfection group was protected on challenge. On day 8 post challenge, at the height of infection and proposed immunopotentiation, the animals were necropsied. Sections from each of the lung lobes were harvested and scored for lung lesions, as demonstrated by histopathology. The high dose FI-RSV vaccine recipients had a two fold increase in the mean lung score of the low dose animals. However, the mean scores of these high dose vaccine animals was comparable to both the placebo vaccine group as well as the infection/reinfection group, indicating that there was no immunpotiation produced by the FI-RSV vaccine. Cytokine levels and flow cytometry also did not indicate any major differences in any of the groups. The lack of immunopotentiation is believed to be due to the Praxis vaccine preparation. Characterization of the preparation is ongoing. A