Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

Abstract

To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-fixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertussis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon γ but not interleukin 4 or interleukin 10 were detected in draining lymph nodes of FFBP-immunized mice. Significantly, repeated immunization of B cell knockout (BKO) mice resulted in partial protection, and complete protection was reconstituted by transfer of pertussis-immune B cells; reconstituted BKO mice had little if any detectable antipertussis antibodies. Immunization of mice lacking all T cells or lacking CD4+ T cells did not lead to protection; in contrast, CD8− mice were protected. Mice depleted of CD4+ T cells after immunization but before aerosol challenge, which thus had normal amounts of specific antibodies, were not optimally protected. Taken together, these data indicate that protective immunity to pertussis is dependent on both CD4+ T cells and B cells, and both cell types provide significant functions other than specific antibody production.

Development of improved vaccines against whooping cough: Current status

“…33,110 Furthermore, immunization of Ig -/-mice with either whole-cell or acellular pertussis vaccines failed to confer protection against an experimental challenge but protection was restored following the transfer of primed B cells. These observations were supported by another study 111 in which intranasal immunisation of Ig -/-mice with formalin-fixed B. pertussis (FFBP) was reported to provide partial protection against an aerosol challenge compared to complete protection in FFBPimmunized wild-type mice. Once again full protection was restored following transfer of immune B cells.…”

“…This has been supported by an observation that the co-administration of IL-12 with an acellular vaccine, which induced a shift in bias from a Th2 to Th1 response, enhanced the rate of clearance following a bacterial challenge. 118 However, given the demonstrated absolute need for antibody in successful clearance 111 and the discovery that B. pertussis can also survive and persist within macrophages and neutrophils 115,116 suggests that both antibody and cell-mediated immune may be central to long term immunity, latter being considered to be associated with cell-mediated immunity (CMI) rather than humoral responses.…”

Assessment of humoral and cell-mediated immunity againstBordetella pertussisin adolescent, adult, and senior subjects in Italy

“…The mechanism of the immune response to B. pertussis involves not only humoral, but also cellularmediated pathways [23,[38][39][40]. According to some authors, the cell-mediated response persists longer than the humoral response and thus CMI can represent an important marker to assess priming against B. pertussis [16,35].…”

Inflammasome Activation by Adenylate Cyclase Toxin Directs Th17 Responses and Protection against Bordetella pertussis

“…Adaptive immunity generated by previous infection or immunization with the whole-cell vaccine is effective at preventing severe disease, and studies in a mouse model suggested that a combination of Abs and Th1 and Th17 cells are involved (3)(4)(5)(6)(7). Protection against a primary infection with B. pertussis is mediated by innate and adaptive immune responses, and IFN-g secreted by NK and Th1 cells seems to be critical (4,8,9). However, host immune responses are suppressed, especially early in infection, because of the induction of regulatory T cells (10), as well as by the various immune-subversion strategies evolved by B. pertussis virulence factors to prolong survival in the host (2,11,12).…”