Background: One of the major obstacles in the development of vaccines to target neutralizing antibody responses is the relative neutralization-resistance of primary HIV-1 isolates. The use of pseudovirions provides a complex antigen source with close to native conformation is one approach that could be taken to develop a safe and effective HIV-1 vaccine. An envelope-containing, heat-treated pseudovirion has a theoretical advantage over a whole-killed vaccine, since it would consist of a complex mixture of immunogenic viral antigens, but could be engineered to be defective in regions important for infectivity, as well as in regions that serve as potential decoys for potent immune responses.

Methods: Mice and non-human primates were vaccinated with envelope-containing, heat-treated pseudovirions and/or whole virions. Mice received 1 vaccination and 3 boosts at 5-week intervals. Non-human primates received 1 vaccination and 2 boosts at 5 weeks intervals. Antibody responses were measured against a panel of primary viruses in MAGI cells and PBMC.

Results: We have previously demonstrated retention of HIV-1 envelope and its major conformational epitopes following thermal treatment of virions and pseudovirions. Moreover, antibody binding to some of these epitopes was significantly enhanced following inactivation. These included potent neutralizing epitopes, some of which have been postulated to be partially occluded or cryptic in native virions. Immunogenicity studies in mice demonstrate the induction of binding antibodies with titers of > 1:500,000. In addition, these antibodies are capable of cross-clade neutralization of HIV in PBMC and MAGI infectivity assays. Non-human primate studies also demonstrate induction of HIV-specific neutralizing antibodies in envelope-containing, heat-treated virions, but not in envelope-deleted virions.

Conclusions: These data suggest that thermal treatment of HIV-1 virions and pseudovirions results in preparations which retain antigenicity in vitro and immunogenicity in vivo. These findings have broad implications for vaccine development.