Safety and Immunogenicity of Newborn MVA85A Vaccination and Selective, Delayed Bacille Calmette-Guerin (BCG) for Infants of HIV Infected Mothers: A Phase 2 Randomized Controlled Trial.
Nemes E., Hesseling AC., Tameris M., Mauff K., Downing K., Mulenga H., Rose P., van der Zalm M., Mbaba S., Van As D., Hanekom WA., Walzl G., Scriba TJ., McShane H., Hatherill M.
Vaccination of HIV-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis (TB) vaccination strategy that protects against TB early in life; and avoids the potential risk of BCG disease until after HIV infection has been excluded.This double-blind randomized controlled trial compared 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.248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen after newborn MVA85A vaccination, but no significant difference was observed in 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. MVA85A vaccination induced modest, but significantly higher Ag85A-specific IFNγ+ CD4+ T cells compared to control at weeks 4 and 8 (p<0.0001). BCG did not further boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNγ+ CD4+ T cell response at weeks 16 and 52 was of similar magnitude in the control arm compared to the MVA85A arm at all time points. Proliferative capacity, functional profiles and memory phenotype of BCG-specific CD4 responses were similar across study arms.MVA85A prime vaccination of HIV-exposed newborns was safe and induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. New protein-subunit and viral-vectored TB vaccine candidates should be tested in HIV-exposed newborns.