Recombinant pro-apoptotic Mycobacterium tuberculosis generates CD8(+) T cell responses against human immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice

摘要

Mycobacterium bovis BCG is an attractive vaccine vector against breast milk HIV transmission because it elicits Th1-type responses in newborns However, BCG causes disease in HIV-infected infants. Genetically attenuated Mycobacterium tuberculosis (Mtb) mutants represent a safer alternative for immunocompromised populations In the current study, we compared the immunogenicity in mice of three different recombinant attenuated Mtb strains expressing an HIV envelope (Env) antigen construct Two of these strains (Delta lysA Delta panCD Mtb and Delta RD1 Delta panCD Mtb) failed to induce significant levels of HIV Env-specific CD8(+) T cell responses In striking contrast, an HIV-1 Env-expressing attenuated Delta lysA Mtb containing a deletion in secA2, which encodes a virulence-related secretion system involved in evading adaptive immunity, generated consistently measurable Env-specific CD8* T cell responses that were significantly greater than those observed after immunization with BCG expressing HIV Env Similarly. another strain of Delta lysA Delta secA2 Mtb expressing SIV Gag induced Gag- and Mtb-specific CD8(+) T cells producing perforin or IFN-gamma, and Gag-specific CD4(+) T cells producing IFN gamma within 3 weeks after immunization in adult mice. in addition, IFN gamma-producing Gag-specific CD8* T cells and Mtb-specific CD4(+) T cells were observed in neonatal mice within I week of immunization We conclude that Delta lysA Delta secA2 Mtb is a promising vaccine platform to construct a safe combination HIV-TB vaccine for use in neonates