Khakhum Nittaya, Bharaj Preeti, Walker David H, Torres Alfredo G, Endsley Janice J
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
NPJ Vaccines. 2021 May 13;6(1):72. doi: 10.1038/s41541-021-00333-4.
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.
类鼻疽病由类鼻疽伯克霍尔德菌（Bpm）引起，目前尚无疫苗。我们确定了马鼻疽伯克霍尔德菌ΔtonBΔhcp1（CLH001）和类鼻疽伯克霍尔德菌ΔtonBΔhcp1（PBK001）疫苗诱导的针对吸入性类鼻疽病的保护性免疫相关因素。用任何一种疫苗进行黏膜免疫均可在血清和肺中产生Bpm特异性IgM和IgG（IgG>IgG>IgG）抗体以及肺IgA抗体。血清具有补体非依赖性杀菌活性和巨噬细胞调理吞噬摄取能力，但在被动转移实验中不足以提供显著保护。两种疫苗在Bpm抗原特异性激发后均能在肺和脾中引发记忆性Th1和Th17 CD4 T细胞反应。PBK001疫苗在加强免疫后产生呼吸道IgA、激发时产生回忆性IgG、对特异性抗原的T细胞激发以及多种多功能记忆T细胞池的形成方面更具优势。肺组织学分析表明，PBK001疫苗接种产生的强效多功能T细胞记忆和/或IL-17特征可能与接种后中度肺部炎症有关。
