434a Prime-Boost Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and Vaccinia Strain DIs Elicits Protective Immunity against Pathogenic SHIV Infection in Macaques' Naoki Yamamoto*1, Tadashi Nakasone2, Yasuyuki Izumi2, Kazuhiro Matsuo2, Yasushi Ami2, Shudo Yamazaki2, Mitsuo Honda2 1National Institute of Infectious diseases,Japan and 2National Institute of Infectious diseases,Japa
Background: Currently, many candidate vaccines against HIV-1 utilize multi-component viral proteins for the induction of strong HIV-specific immune responses. However, the potential of SIV candidate vaccines expressing single viral proteins has not been fully explored. Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo strain was proven safe and effective when used in humans as a vaccine against tuberculosis. Similarly, a highly attenuated vaccinia strain DIs was confirmed to be non-replicative in any mammalian cells tested. We further found vaccine vectors could be safe in immune deficient animals.
Methods: BCG-Tokyo and vaccinia DIs -based vectors were developed to express full-length gag from simian immunodeficiency virus rBCG-SIVgag and rDIs-S IVgag, respectively.
Results: Cynomologus macaques were vaccinated by various routes with either rBCG-SIVgag as a single modality or in combination with a replication-deficient vaccinia strain DIs expressing SIV gag (rDIs-SIVgag). Protective immunity ag ainst a highly pathogenic SHIV (SHIV-C2/1) was elicited by a combination regimen consisting of rBCG-SIVgag priming, followed by boosting with rDIs-SIVgag. Preexisting immunity to BCG did not significantly affect the efficacy of the combination regimen. Our results also demonstrate that preexisting immunity to BCG has little or no effect on the ability of rBCG-SIVgag to induce effective protective immunity.
Conclusions: These results demonstrate that a recombinant BCG-based vector has potential as an HIV/AIDS vaccine when administered in combination with a replication deficient vaccinia DIs vector in a prime-boost strategy..