Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants

Vaccine. 2015 Sep 11;33(38):4782-9. doi: 10.1016/j.vaccine.2015.07.096. Epub 2015 Aug 7.


Background: Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants.

Methods: Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens.

Results: Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age.

Conclusion: Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants.

Clinical trial registry: NCT02062580.

Keywords: BCG vaccine; HIV; Infants; Pertussis; T cell; Tetanus.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • BCG Vaccine / administration & dosage*
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Environmental Exposure*
  • Female
  • HIV Infections*
  • Humans
  • Immunization Schedule*
  • Infant
  • Male
  • Pertussis Vaccine / administration & dosage
  • Pertussis Vaccine / immunology*
  • T-Lymphocytes / immunology*
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology*
  • Time Factors


  • BCG Vaccine
  • Cytokines
  • Pertussis Vaccine
  • Tetanus Toxoid

Associated data