Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries

Sci Rep. 2018 Oct 17;8(1):15309. doi: 10.1038/s41598-018-33499-4.

Abstract

In the absence of a more effective vaccine against TB and in the interest of developing one, it is essential to understand immune responses associated with BCG protection. We comprehensively characterized T cell populations in BCG-vaccinated children over time. Blood from 78 healthy, BCG-vaccinated children representing four age groups (<1 yr, ≥1 yr <2 yr, ≥2 yr <5 yr, ≥5 yr), was stimulated in vitro for 24 hours and 6 days with live BCG to induce effector and central memory responses. Antigen-specific CD4, CD8, γδ and regulatory T cell populations were phenotyped and intracellular and secreted cytokines measured by flow cytometry and multiplex ELISA respectively. Our results demonstrated that populations of naïve T cells predominated in infants, compared to older children. However, BCG-specific effector CD4 T cell responses were equivalent and antigen-specific CD4 T cell proliferative capacity was increased in infants compared to older children. Increases in innate immune responses including γδ T cell responses and secreted pro-inflammatory cytokines were noted with increasing age. In conclusion, we identified that the capacity to expand and differentiate effector T cells in response to BCG stimulation wanes with increasing age, which may indicate waning central memory immunity. Booster vaccination could be considered to maintain the antigen-specific central memory pool and possibly enhance the duration of protection.

Publication types

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

MeSH terms

  • Age Factors
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Immunologic Memory / immunology
  • Infant
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / physiology
  • T-Lymphocytes, Regulatory / immunology*
  • Time Factors
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Vaccination / methods

Substances

  • BCG Vaccine
  • Cytokines