The Role of Mucosal Immunity in Pertussis

Abstract

Pertussis or whooping cough, mainly caused by Bordetella pertussis, is a severe respiratory disease that can affect all age groups but is most severe and can be life-threatening in young children. Vaccines against this disease are widely available since the 1950s. Despite high global vaccination coverage, the disease is not under control in any country, and its incidence is even increasing in several parts of the world. Epidemiological and experimental evidence has shown that the vaccines fail to prevent B. pertussis infection and transmission, although they are very effective in preventing disease. Given the high infection rate of B. pertussis, effective control of the disease likely requires prevention of infection and transmission in addition to protection against disease. With rare exceptions B. pertussis infections are restricted to the airways and do not usually disseminate beyond the respiratory epithelium. Therefore, protection at the level of the respiratory mucosa may be helpful for an improved control of pertussis. Yet, compared to systemic responses, mucosal immune responses have attracted relatively little attention in the context of pertussis vaccine development. In this review we summarize the available literature on the role of mucosal immunity in the prevention of B. pertussis infection. In contrast to vaccination, natural infection in humans and experimental infections in animals induce strong secretory IgA responses in the naso-pharynx and in the lungs. Several studies have shown that secretory IgA may be instrumental in the control of B. pertussis infection. Furthermore, studies in mouse models have revealed that B. pertussis infection, but not immunization with current acellular pertussis vaccines induces resident memory T cells, which may also contribute to protection against colonization by B. pertussis. As these resident memory T cells are long lived, vaccines that are able to induce them should provide long-lasting immunity. As of today, only one vaccine designed to induce potent mucosal immunity is in clinical development. This vaccine is a live attenuated B. pertussis strain delivered nasally in order to mimic the natural route of infection. Due to its ability to induce mucosal immunity it is expected that this approach will contribute to improved control of pertussis.

Development and Validation of a Bordetella pertussis Whole-Genome Screening Strategy

“…Higher levels of antibody against ACT have also been observed in the plasma of aP-primed donors (unpublished observations). Thus, aP-vaccinated subjects are associated with immune responses against a variety of BP antigens not just present in the aP vaccine, which is consistent with the notion that aP prevents disease but not BP colonization/exposure [18,19,21].…”

“…Several lines of evidence argue against this simplistic view, which are related to the possible interplay between vaccination and natural BP exposure/infection [16]. Specifically, recent data from both baboon and mouse models [15,[17][18][19][20][21] suggests that aP vaccination might prevent disease but not infection or in particular nasopharyngeal subclinical colonization. This might paradoxically result in broad responses in aP and is of greater magnitude than wP because of heavier and more frequent exposure.…”

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

“…Therefore, reducing nasal carriage by immunization is an important goal to prevent transmission and lowering the risk of exposure especially to unvaccinated individuals. Induction of mucosal immunity in the respiratory tract and particularly in the nasal cavity could assist preventing nasal colonization by B. pertussis and therefore reducing the chance of transmission 7 . B. pertussis infections induce powerful mucosal immunoglobulin A (IgA) and T helper (Th) type 17-mediated responses and prevent colonization in the complete respiratory tract upon reinfection 8,9 .…”

“…In addition, the immune response after intranasal immunization with the live-attenuated pertussis vaccine BPZE1 is also characterized by Th17 and IgA responses and this vaccine diminishes the capability of B. pertussis to colonize the nose 10 . Mucosal immunity might therefore be an important mechanism to prevent nasal carriage and reduce the risk for transmission 7 .…”

Papel del estado de portador en el control de enfermedades infecciosas y su relación con la vacunación

“…Esta respuesta es importante en el control de la infección. (34) La incidencia de tosferina ha aumentado desde la introducción de las vacunas acelulares. Estas vacunas, en contraste con las vacunas de células completas, no generan inmunidad en mucosas y no otorgan inmunidad de grupo.…”