Protein energy malnutrition during vaccination has limited influence on vaccine efficacy but abolishes immunity if administered during Mycobacterium tuberculosis infection

Infect Immun. 2015 May;83(5):2118-26. doi: 10.1128/IAI.03030-14. Epub 2015 Mar 9.

Abstract

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of Mycobacterium tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ(+) TNF-α(+) and IFN-γ(+) cells). PEM during M. tuberculosis infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against M. tuberculosis infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / metabolism
  • Female
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology
  • Protein-Energy Malnutrition / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis Vaccines / immunology*
  • Vaccination / methods*

Substances

  • Cytokines
  • Tuberculosis Vaccines