Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines.

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_2b/c> IgG₁ > IgG₃) 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.

SUBMITTER: Khakhum N 

PROVIDER: S-EPMC8119421 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature