The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis

Abstract

The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed.

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

“…For ex vivo determinations, the same combination of cytokines was used after 20 h incubation with lysate (10 μg/mL), epitope pools (2 μg/mL), or individual peptides (10 μg/mL) besides PHA (2 μg/mL) and DMSO as positive and negative controls, respectively. Consistent with these previous studies in order to be considered positive, a response in both in vitro or ex vivo modalities had to match all three different criteria: (1) [35][36][37][38], as observed in animal models [19,21], which could affect T cell responses against BP antigens to a greater extent than originally expected. To address this issue, we examined memory CD4 responses to a previously defined peptide pool of BP epitopes encompassing the 4 antigens (FHA, Fim2/3, PRN, and PtTox) contained in the aP vaccine [10] in a set of PBMCs derived from 31 donors either originally vaccinated with aP (n = 16) or originally vaccinated with wP (n = 15).…”

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

“…Indeed, evolutionary shifts favoring novel alleles for virulence factors, poor vaccination rates, and/or vaccine refusals and detection bias due to enhanced diagnostic techniques have been proposed (8)(9)(10)(11). Conversely, an emergent picture associated with differential mucosal immunity seems to offer a better explanation (9,(12)(13)(14)(15); however, human studies are lacking.…”

Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

“…The Gram-negative, aerobic coccobacillus Bordetella pertussis is the causative agent of whooping cough (pertussis), a highly contagious infectious disease of the respiratory tract with high mortality in newborns and infants. While pertussis is a vaccine preventable disease, the incidence of pertussis has been increased in many countries during the last decade, despite high vaccine coverage ( 1 , 2 ). It has been hypothesized that the resurgence of pertussis reflects ineffective or waning immunity induced by current acellular pertussis (aP) vaccines, as well as the emergence of strains of B. pertussis with mutations or deletion of antigens in the aP vaccines ( 2 , 3 ).…”