HIV-1 sequencing from humanized mice

BLT (bone marrow, liver, thymus) humanized mice, which reconstitute a functional human immune system, develop prototypic human virus-specific CD8+ T cell responses following infection with HIV-1. We explored the utility of the BLT model for HIV-1 vaccine development by immunizing BLT mice against the conserved viral Gag protein utilizing a rapid prime-boost protocol of PLGA microparticles and a replication-defective HSV recombinant vector. After HIV-1 challenge, the mice developed broad, proteome-wide IFN-?+ T cell responses against HIV-1 that reached magnitudes equivalent to what is observed in HIV-1 infected individuals. The functionality of these responses was underscored by the consistent emergence of escape mutations in multiple CD8+ T cell epitopes during the course of infection.