Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective BurkholderiaΔtonBΔhcp1 live attenuated vaccines

Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei Delta tonB Delta hcp1 (CLH001) and Bpm Delta tonB Delta hcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG(2)(b/c )> IgG(1) > IgG(3)) 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.

Automated summary

The study identified immune correlates of protection induced by B. mallei Delta tonB Delta hcp1 and Bpm Delta tonB Delta hcp1 vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generated specific antibodies and memory T-cell responses in lung and spleen. PBK001 vaccine showed superiority in generating respiratory IgA, anamnestic IgG, T-cell recall, and diverse memory T-cell pools.