8 research outputs found
Mamu-Aâ01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development
AbstractWe have developed a murine model expressing the rhesus macaque (RM) Mamu-Aâ01 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 (α1 and α2 Mamu-Aâ01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-Aâ01/Kb Tg mice with rVV-SIVGagâPol, the mice generated CD8+ T-cell IFN-Îł responses to several known Mamu-Aâ01 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-SIVGagâPol challenge. Mamu-Aâ01/Kb Tg mice provide a model system to study the Mamu-Aâ01 restricted T-cell response for various infectious diseases which are applicable to a study in RM