Vaccination of HIV-infected infants with the Bacille Calmette-Guérin (BCG) against tuberculosis (TB) is currently contraindicated. The authors were interested in a new TB vaccine strategy to reduce the risk of TB in HIV-exposed newborns and avoid the potential risk of BCG disease. They performed a double-blind randomised controlled trial in which newborn MVA85A prime vaccination (1 x10^8 PFU) was compared with a CANDIN (Candida albicans Skin Test Antigen for Cellular Immunity) control, followed by selective deferred BCG vaccination at 8 weeks of age for HIV-uninfected infants, and 12 months follow-up for safety and immunogenicity. 248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen following newborn MVA85A vaccination but no significant difference was observed in the rate of severe or serious adverse events, HIV acquisition, or incident TB disease (n=5 MVA85A, n=3 control) compared with the control arm. MVA85A vaccination induced modest but significantly higher Ag85A-specific IFNγ+ CD4+ T cells compared with the control at weeks 4 and 8. BCG did not further boost this response in MVA85A recipients. The BCG-induced Ag85A-specific IFNγ+ CD4+ T cell response at weeks 16 and 52 was of similar magnitude in the control arm compared with the MVA85A arm. Proliferative capacity, functional profiles and memory phenotype of BCG-specific CD4+ T cell responses were similar in the two study arms. Therefore MVA85A prime vaccination of HIV-exposed newborns is safe and induces an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination.
Read more here