Antigen Recognition after Mycobacterium Tuberculosis Challenge of Mice Vaccinated with Intravenous Bcg

Abstract

Bacille Calmette-Guerin (BCG) is the only approved vaccine against tuberculosis but the subcutaneous route does not provide for the elimination of Mycobacterium tuberculosis (Mtb), thus highlighting the need for investigating other routes of administration. We used a unique set of 60 peptide pools with unprecedented coverage of the bacterium that had previously been used to study T cell responses in subjects latently infected with Mtb. We showed that intravenous BCG vaccination of C57BL/6 mice elicited a more robust IFN-γ response from splenocytes than the subcutaneous route, with the highest responses driven by the Ag85A/B and PE/PPE family epitopes, followed by TB10.4 and Esx-1. We then compared the spectrum of antigen recognition in BCG-naïve H37Rv-challenged and BCG-vaccinated H37Rv-challenged mice. Peptides belonging to TB10.4, ESAT-6, CFP-10, Ag85A/Ag85B, PE/PPE and Esx families up-regulated IFN-γ production in the lungs of BCG-naïve H37Rv-challenged mice but the response was much lower in the BCG-vaccinated group.

Note:
Funding Information: The work was funded by the Division of Pulmonary and Critical Care Medicine in the Department of Medicine at NYU Grossman School of Medicine and also by a foundation grant from the Stony Wold Herbert Inc., Foundation.

Declaration of Interests: None to declare.

Ethics Approval Statement: The study was done in accordance with the NIH guidelines and after approval by the NYU Grossman School of Medicine Institutional Animal Care and Use Committee.

Keywords: T cell response, IFN-γ, TB