AERAS-402/Ad35 vaccine induces CD4+ and CD8+ responses in HIV-infected, BCG-vaccinated adults (P4487)

Abstract

Abstract One-third of the world's population is estimated to be infected with TB. The WHO no longer recommends that the currently available TB vaccine, BCG, be given to infants born to HIV+ mothers due to safety concerns. An improved vaccine that is effective and safe for HIV+ infants is needed to protect this vulnerable population. AERAS-402 is a novel replication deficient Ad35 TB vaccine candidate that expresses a fusion protein of the Mtb antigens 85A, 85B, and TB10.4 and has been shown to safely induce CD8+ T cell responses in healthy adults. This study examined the safety and immunogenicity of a single IM dose of AERAS-402 in HIV+ adults. No vaccine-related serious adverse events were reported, suggesting the vaccine is safe in this population. CD4+ and CD8+ T cell responses were evaluated using ICS. Prior studies in healthy adults revealed primarily CD8+ responses to vaccination with AERAS-402. Vaccination of HIV+ adults resulted in the elicitation of both CD4+ and CD8+ responses of ~0.1% to 0.2% of the parent population largely directed to 85A and 85B. CD4+ responses were primarily polyfunctional (IFN-γ, IL-2, and TNF) and bifunctional (IL-2 and TNF) while CD8+ responses were largely bifunctional (IFN-γ and TNF) and monofunctional (IFN-γ) with lower levels of polyfunctional cells observed. Together the data suggest that vaccination with AERAS-402 in HIV+ adults is safe and immunogenic, resulting in a mixed CD4+ and CD8+ multifunctional T cell response to encoded antigens.