Heterologous prime-boost with Ad35/AERAS-402 and MVA85A elicits potent CD8+ T cell immune responses in a phase I clinical trial (VAC7P.969)

Abstract Developing an effective vaccine to prevent pulmonary tuberculosis represents a public health priority. AERAS-402 (adenovirus expressing a fusion of M.tuberculosis antigens 85A, 85B, and TB10.4) and MVA85A (Modified Vaccinia Anakara expressing Ag85A) are TB vaccine candidates that have been independently evaluated in adult and infant studies and shown to be safe and immunogenic. Despite robust immune responses in adults, infant trials have revealed lower than expected immunogenicity for these vaccine platforms, possibly contributing to the failure of the MVA85A vaccine in a recent phase II efficacy trial. Complimentary studies of malaria and HIV vaccines report enhanced immune responses using heterologous vaccine approaches with combinations of adenoviral and pox virus vectors. Here we present the preliminary immunogenicity data from a phase I clinical trial conducted in healthy BCG-vaccinated adults that were vaccinated with one or two doses of AERAS-402 and subsequently boosted with MVA85A. Preliminary data indicate that MVA85A boosts both CD4+ and CD8+ T cell responses. Interestingly, MVA85A, which primarily stimulates CD4+ T cell responses when given alone,robustly boosted AERAS-402 CD8+ T cell responses to Ag85A, with average responses reaching approximately 0.5% to 1% of CD8+ T cells. These data suggest that this vaccine combination is highly immunogenic in adults. Further studies are needed to assess the clinical efficacy of this vaccine combination.