Mamu-A01/K(b) transgenic and MHC Class I knockout mice as a tool for HIV vaccine development

We have developed a murine model expressing the rhesus macaque (RM) Mamu-A01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (alpha1 and alpha2 Mamu-A01 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2K(b) domains) MHC Class I molecules were derived by transgenesis of the H-2K(b)D(b) double MHC Class I knockout strain. After immunization of Mamu-A01/K(b) Tg mice with rVV-SIVGag-Pol, the mice generated CD8(+) T-cell IFN-gamma responses to several known Mamu-A01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A01/K(b) Tg mice provide a model system to study the Mamu-A01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.