Antigen-specific Antibody and Polyfunctional T Cells Generated by Respiratory Immunization with Protective Burkholderia ΔtonB Δhcp1 Live Attenuated Vaccines

Overview

Journal NPJ Vaccines

Date 2021 May 14

PMID 33986290

Citations 10

Authors

Nittaya Khakhum

Preeti Bharaj

David H Walker

Alfredo G Torres

Janice J Endsley

Affiliations

Soon will be listed here.

Abstract

Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG> IgG > IgG) antibodies in sera and lungs, and lung IgA antibodies. Sera confers complement-independent bactericidal activity and macrophages opsonophagocytic uptake but is insufficient in passive transfer experiments to provide significant protection. Both vaccines elicit memory Th1 and Th17 CD4 T-cell responses in lung and spleen after Bpm antigen-specific recall. The PBK001 vaccine is superior in generating respiratory IgA post-boost, anamnestic IgG at challenge, T-cell recall to specific antigen, and development of diverse polyfunctional memory T-cell pools. Analysis of lung histology suggests that potent polyfunctional T-cell memory and/or IL-17 signatures generated with PBK001 vaccination may be associated with moderate lung inflammation post vaccination.

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