Mucosal vaccination with an attenuated strain of Mycobacterium tuberculosis induces a strong central memory response and protects non-human primates against lethal challenge (VAC4P.1104)

Abstract

Abstract There is an urgent need for new vaccine(s) that protect efficiently against Mycobacterium tuberculosis (Mtb), as well as, to better understand the correlates of a protective host response to Mtb infection. Aerosol infection of macaques with the redox-stress deficient mutant, Mtb:Δ-sigH, resulted in the recruitment of significantly more inducible bronchus-associated lymphoid tissue, which is associated with protection from Mtb infection in mice, macaques, and humans. We therefore hypothesized that vaccination with Mtb:Δ-sigH could protect against a lethal Mtb challenge significantly better than a comparable Bacille Calmette-Guerin (BCG) vaccination. A single vaccination of the aerosol delivered, live-attenuated strain completely protected macaques from lethal Mtb challenge. Protection was associated with three-to-four log lower bacterial burden, significantly reduced granulomatous pathology and clinical features of Mtb infection, as well as, a strong T cell central memory response when compared to BCG-vaccinated animals. A higher magnitude, as well as, breadth of polyfunctional T cell responses was detected in the Mtb:Δ-sigH vaccinated animals. This includes an increased recruitment and turnover of central and effector T cells in the lung post vaccination compared to BCG-vaccinated animals. These results point to the protective qualities induced by a live-attenuated mucosal vaccine for protection against lethal Mtb challenge, and its future in TB vaccine initiatives.