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

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

Author information

1
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
2
Veterinary Sciences Centre, School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland.
3
International Health, Immunology and Microbiology, The Panum Institute, Copenhagen, Denmark.
4
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark PA@ssi.dk.

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.

PMID:
25754202
PMCID:
PMC4399034
DOI:
10.1128/IAI.03030-14
[Indexed for MEDLINE]
Free PMC Article

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