Immunization with whole cell but not acellular pertussis vaccines primes CD4 T _RM cells that sustain protective immunity against nasal colonization with Bordetella pertussis

Abstract

Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (T RM ) cells in persistent protective immunity induced by infection or immunization with aP and whole-cell pertussis (wP) vaccines in mice. Immunization of mice with a wP vaccine protected against lung and nasal colonization, whereas an aP vaccine failed to protect in the nose. IL-17 and IFN-γ-secreting CD69 + CD4 + T RM cells were expanded in the lung and nasal tissue after B. pertussis challenge of mice immunized with wP, but not aP vaccines. However, previous infection induced the most persistent protection against nasal colonization and this correlated with potent induction of nasal tissue T RM cells, especially IL-17-secreting T RM cells. Blocking T cell migration to respiratory tissue during immunization with a wP vaccine impaired bacterial clearance, whereas transfer of T RM cells from convalescent or wP-immunized mice conferred protection to naïve mice. Our findings reveal that previous infection or wP vaccination are significantly more effective than aP vaccination in conferring persistent protective immunity against B. pertussis and that this is mediated by respiratory T RM cells.

Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization

“…A protective role for CD4 + T RM at mucosal surfaces has recently been described for a number of bacterial pathogens of public health significance. 1,2,[28][29][30][31][32][33][34] Exposure to live pneumococcus in the nasopharynx protects mice against subsequent homologous or heterologous pneumococcal challenge. 21,22 Hence, we hypothesized that I.N.…”

Vaccination against Paediatric Respiratory Pathogens

“…Moreover, earlier waning of protective immunity and the circulation of B. pertussis variants depleted of vaccine-included antigens further favor the increase in pertussis disease [74]. Studies in immunized children have reported that antibody responses and protective immunity wane 3-5 years after immunization with acellular pertussis (aP) vaccines, which may reflect poor induction of memory T and/or B cells [76][77][78].…”

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

“…Yet another cause for the increase is the differences detected in the immune response triggered by the whole cell vaccine (Th17) vs. the acellular vaccine (Th2) (51,(55)(56)(57). It is important to highlight that while neither whole-cell nor acellular vaccines confer long-lasting immunity, and the merits of both responses have been debated in recent years, the general consensus agrees on advantages to skewing T cell response toward Th1/Th17 immunity (58)(59)(60)(61).…”