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Melioidosis, caused by  Burkholderia pseudomallei  ( Bpm ), lacks a vaccine. We identify the immune correlates of protection induced by  B. mallei  Δ tonB  Δ hcp1  (CLH001) and  Bpm  Δ tonB  Δ 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.

npj vaccines

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