Intravenous BCG driven antigen recognition in a murine tuberculosis model.

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Bacille Calmette-Guerin (BCG) is the sole vaccine for tuberculosis, but its efficacy is limited by the subcutaneous administration route.
• Investigating alternative administration routes for BCG is crucial for enhancing Mycobacterium tuberculosis (Mtb) protection.

Purpose of the Study:

• To compare the immunogenicity of intravenous (IV) versus subcutaneous (SC) BCG vaccination in mice.
• To characterize T cell responses to a comprehensive panel of Mtb antigens at the epitope level.
• To identify key Mtb antigens involved in T cell recognition following vaccination and challenge.

Main Methods:

• C57BL/6 mice were vaccinated with BCG via IV and SC routes.
• Splenocytes and lung cells were stimulated with a 60-peptide pool covering diverse Mtb antigens.
• Interferon-gamma (IFN-γ) production was measured as a marker of T cell response.
• Antigen recognition was compared between BCG-naïve and BCG-vaccinated mice challenged with H37Rv.

Main Results:

• Intravenous BCG vaccination elicited a more robust IFN-γ response from splenocytes compared to the subcutaneous route.
• The Ag85A/B and PE/PPE families, followed by TB10.4 and Esx-1 epitopes, drove the highest IFN-γ responses after IV BCG.
• BCG vaccination significantly reduced the IFN-γ response to several Mtb antigens (TB10.4, ESAT-6, CFP-10, Ag85A/B, PE/PPE, Esx) in the lungs upon H37Rv challenge.

Conclusions:

• Intravenous administration of BCG enhances T cell immunogenicity compared to the conventional subcutaneous route.
• A broad Mtb antigen panel reveals specific epitopes that elicit strong T cell responses, aiding in understanding vaccine efficacy.
• Further research correlating epitope-specific T cell responses with bacterial load reduction is needed to define protective antigens.