Abstract
Immunization with current acellular pertussis (aP) vaccines protects against severe pertussis, but immunity wanes rapidly after vaccination and these vaccines do not prevent nasal colonization with Bordetella pertussis. Studies in mouse and baboon models have demonstrated that Th1 and Th17 responses are integral to protective immunity induced by previous infection with B. pertussis and immunization with whole cell pertussis (wP) vaccines. Mucosal Th17 cells, IL-17 and secretory IgA (sIgA) are particularly important in generating sustained sterilizing immunity in the nasal cavity. Current aP vaccines induce potent IgG and Th2-skewed T cell responses but are less effective at generating Th1 and Th17 responses and fail to prime respiratory tissue-resident memory T (TRM) cells, that maintain long-term immunity at mucosal sites. In contrast, a live attenuated pertussis vaccine, pertussis outer membrane vesicle (OMV) vaccines or aP vaccines formulated with novel adjuvants do induce cellular immune responses in the respiratory tract, especially when delivered by the intranasal route. An increased understanding of the mechanisms of sustained protective immunity, especially the role of respiratory TRM cells, will facilitate the development of next generation pertussis vaccines that not only protect against pertussis disease, but prevent nasal colonization and transmission of B. pertussis.
Highlights
Pertussis, or whooping cough, is caused by the Gram-negative bacterium Bordetella pertussis, which infects the upper and lower respiratory tract, causing considerable morbidity in children and adults and severe disease that can be fatal in infants [1]
A live attenuated pertussis vaccine, pertussis outer membrane vesicle (OMV) vaccines or acellular pertussis (aP) vaccines formulated with novel adjuvants do induce cellular immune responses in the respiratory tract, especially when delivered by the intranasal route
dendritic cells (DCs) activation and Th1 cytokine production was enhanced before and after B. pertussis challenge in mice treated with c-di-GMP [204]. These findings demonstrated the central role of innate immune stimulation in generating a protective immunity against B. pertussis and suggested that c-di-GMP could be a viable adjuvant for a pertussis vaccine
Summary
Whooping cough, is caused by the Gram-negative bacterium Bordetella pertussis, which infects the upper and lower respiratory tract, causing considerable morbidity in children and adults and severe disease that can be fatal in infants [1]. Studies in mouse models have shown that in the bactericidal stage, inflammatory macrophages and DCs infiltrate the lung from the periphery In addition to their function as antigen presenting cells (APCs), DCs produce pro-inflammatory cytokines and chemokines in response to PAMPs, including LPS binding to TLR4, that promote the recruitment and activation of other innate immune cells and effector T cells. Neutrophil numbers peak in the lung at 5-7 days post challenge in mice, and have the capacity to phagocytose and kill B. pertussis, but are not essential for clearance of bacteria from the lungs during primary infection [49,50] They do, play an important role in the protection of immune mice from reinfection, which is believed to be due to bacterial killing via antibody-mediated phagocytosis [49]. In the memory stage, following clearance of B. pertussis from the respiratory tract, the number of effector T and B cells contracts, but populations of memory B and T cells are generated and persist to maintain long-lived immunity against re-infection [37,55,56]
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