Background: The molecules of the major histocompatibility complex (MHC) are prominent among cellular proteins incorporated in the virion of both HIV and SIV. MHC molecules are immunogenic and vary significantly between individuals, yet are not subject to rapid mutation unlike viral proteins, so they are potential immune targets on the virus envelope. We used the SIV/macaque model to test a vaccine designed to induce allo-immune responses against MHC in order to determine if this is a viable approach for a preventative HIV vaccine.

Methods: Twelve (12) mA*01 and DRw201 negative Rhesus macaques were randomized to receive vaccine or placebo. A Rhesus macaque that was mA*01 and DRw201 positive was designated as the index monkey. MamuA*01 and DRw201 genes were cloned from the index monkey. DNA priming vectors were developed using dual cassette plasmids containing mA*01 or DRw201, along with the co-stimulatory molecule CD86. Vaccinia (strain NYVAC) virus vectors containing these same allo-antigens were also constructed. Protein immunogens of mA*01 and DRw201 were expressed using the baculovirus-insect system and purified using immuno-affinity chromatography. The prime boost immunization schedule included two immunizations with DNA vectors, one with the NYVAC vector, and three with MHC protein immunogens either mucosally or systenetically. Challenge was performed with SIV derived from index monkey’s PBMC 4 weeks after the final protein boost.

Results: Serum and mucosal alloantibody responses over the course of the immunization protocol have been monitored. We report here immunogenicity data: Very vigorous humoral anti-MHC antibody responses, with endpoint IgG titer in the millions and endpoint IgA titer in the thousands, can be generated using this double-prime boost approach. We will present the primary study endpoint (sterilizing immunity), and other secondary endpoints including laboratory and clinical evidence of disease progression among animals receiving vaccine versus placebo.

Conclusions: Efficient MHC allo-immune responses in rhesus macaques can be achieved by the combination of DNA vaccine, NYVAC vector and protein antigens. If these provide protective immunity, this approach can be adapted to contain common HLA antigens in order to evaluate safety and protective efficacy against a variety of strains of HIV-1 and HIV-2 in humans.