Optimizing HIV‐1‐specific CD8+ T‐cell induction by recombinant BCG in prime‐boost regimens with heterologous viral vectors

AbstractThe desire to induce HIV‐1‐specific responses soon after birth to prevent breast milk transmission of HIV‐1 led us to propose a vaccine regimen which primes HIV‐1‐specific T cells using a recombinant Mycobacterium bovis bacillus Calmette‐Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand‐alone vaccines, rBCG‐primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS‐401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV‐1‐specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA401 and BCG.HIVA222 primed HIV‐1‐specific CD8+ T‐cell‐mediated responses. The strongest boosts were delivered by human adenovirus‐vectored HAdV5.HIVA and sheep atadenovirus‐vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime‐boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA401 and BCG.HIVA222 vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV‐1‐ and BCG‐specific stimuli. These results encourage further development of the rBCG prime‐boost regimen.