The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol [i]Mycobacterium tuberculosis[/i] infection - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Vaccine Année : 2016

The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol [i]Mycobacterium tuberculosis[/i] infection

Résumé

Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection. Ag85B was required for macrophage infection in vitro, as BCG deficient in Ag85B expression (BCG:Delta85B) was less able to infect RAW 264.7 macrophages compared to parental BCG, while an Ag85B-overexpressing BCG strain (BCG:oex85B) demonstrated improved uptake. A similar pattern was observed in vivo after intradermal delivery to mice, with significantly less BCG:Delta85B present in CD64hiCD11bhi macrophages compared to BCG or BCG:oex85B. After vaccination of mice with BCG:Delta85B or parental BCG and subsequent aerosol M. tuberculosis challenge, similar numbers of activated CD4+ and CD8+ T cells were detected in the lungs of infected mice for both groups, suggesting the reduced macrophage uptake observed by BCG:Delta85B did not alter host immunity. Further, vaccination with both BCG:Delta85B and parental BCG resulted in a comparable reduction in pulmonary M. tuberculosis load. These data reveal an unappreciated role for Ag85B in the interaction of mycobacteria with host cells and indicates that single protective antigens are dispensable for protective immunity induced by BCG.
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Dates et versions

hal-01324360 , version 1 (31-05-2016)

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K. A. Prendergast, C. Counoupas, L. Leotta, C. Eto, W. Bitter, et al.. The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol [i]Mycobacterium tuberculosis[/i] infection. Vaccine, 2016, 34 (23), pp.2608-2615. ⟨10.1016/j.vaccine.2016.03.089⟩. ⟨hal-01324360⟩
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