Nemes E, et al. - Authors in this Phase 2 randomized controlled trial assessed the safety and immunogenicity of newborn MVA85A vaccination and selective, delayed Bacille Calmette-Guerin (BCG) for infants of HIV infected mothers. Findings demonstrated that MVA85A prime vaccination of HIV-exposed newborns was safe induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. They recommended testing new protein-subunit and viral-vectored TB vaccine candidates in HIV-exposed newborns.

Methods

• In this double-blind randomized controlled trial, a comparison was performed of newborn MVA85A prime vaccination (1 x10 8 PFU) vs. Candin 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.

Results

• This trial enrolled 248 HIV-exposed infants.
• There appeared more frequent mild-moderate reactogenicity events after newborn MVA85A vaccination, however there was no significant difference regarding the rate of Severe or Serious Adverse Events; HIV acquisition (n=1 per arm); or incident TB disease (n=5 MVA85A; n=3 control) compared to the control arm.
• At weeks 4 and 8, MVA85A vaccination seemed inducing modest, but markedly higher Ag85A-specific IFNγ+ CD4+ T cells compared to control (p<0.0001).
• In MVA85A vaccinees, BCG did not further boost this response.
• At weeks 16 and 52, the BCG-induced Ag85A-specific IFNγ+ CD4+ T cell response was of similar magnitude in the control arm compared to the MVA85A arm at all time points.
• Across study arms, proliferative capacity, functional profiles and memory phenotype of BCG-specific CD4 responses were comparable.