Acellular Pertussis Vaccine Inhibits Bordetella pertussis Clearance from the Nasal Mucosa of Mice

Abstract

Bordetella pertussis whole-cell vaccines (wP) caused a spectacular drop of global pertussis incidence, but since the replacement of wP with acellular pertussis vaccines (aP), pertussis has resurged in developed countries within 7 to 12 years of the change from wP to aP. In the mouse infection model, we examined whether addition of further protective antigens into the aP vaccine, such as type 2 and type 3 fimbriae (FIM2/3) with outer membrane lipooligosaccharide (LOS) and/or of the adenylate cyclase toxoid (dACT), which elicits antibodies neutralizing the CyaA toxin, could enhance the capacity of the aP vaccine to prevent colonization of the nasal mucosa by B. pertussis. The addition of the toxoid and of the opsonizing antibody-inducing agglutinogens modestly enhanced the already high capacity of intraperitoneally-administered aP vaccine to elicit sterilizing immunity, protecting mouse lungs from B. pertussis infection. At the same time, irrespective of FIM2/3 with LOS and dACT addition, the aP vaccination ablated the natural capacity of BALB/c mice to clear B. pertussis infection from the nasal cavity. While wP or sham-vaccinated animals cleared the nasal infection with similar kinetics within 7 weeks, administration of the aP vaccine promoted persistent colonization of mouse nasal mucosa by B. pertussis.

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

“…Furthermore, given that the wP vaccine contains >3400 open-reading frames, whereas the aP vaccine includes only five or fewer Bp proteins, it is likely that the former elicits a broader reactivity and targets additional surface antigens, some of which might be of particular relevance and linked to superior vaccine performance [ 46 , 47 ]. This potentially underlies differences observed in the breadth of antibody responses and/or functional antibodies induced: primarily PT-neutralising compared to a combination of neutralising, agglutinating and opsonising antibodies following aP and wP vaccines, respectively [ 48 , 49 , 50 ]. However, to date, the extent and targets of T-cell immunity in the context of natural infection, clinical disease or vaccination have not been comprehensively defined.…”

A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy

“…Bordetella pertussis colonization in humans was shown to induce a systemic immune response without causing clinical (whooping cough) symptoms in a controlled human infection study ( 59 ). Also, it is known that colonization can occur after aP but not wP vaccination in mice and baboon models ( 12 , 30 , 60 ), which would explain why the same subgroup is not seen in wP-primed individuals. This hypothesis will need to be addressed in future studies by directly assessing subclinical colonization using nasal swab collections for PCR-based detection of Bordetella pertussis and assessing its impact on the immune response.…”

The Path to New Pediatric Vaccines against Pertussis

“…Most importantly, however, while protective against pertussis disease, pertussis vaccination has at best limited effects on the prevention of colonization by and transmission of B. pertussis [26]. Furthermore, experimental studies in baboons and mice suggest that acellular pertussis vaccination may result in prolonged nasal carriage of B. pertussis [26][27][28][29].…”

“…The recently developed baboon model recapitulates the nearly full spectrum of human pertussis, including paroxysmal cough [39] and airborne transmission of B. pertussis from animal to animal [49]. aP vaccination of baboons protected these animals from pertussis disease, but did not prevent infection and transmission [26], and in fact, similar to mice [27][28][29], prolonged nasal carriage of B. pertussis. In contrast, wP vaccination did not prolong nasal carriage in baboons, which cleared the infection faster than non-vaccinated baboons, although much less efficiently than convalescent baboons [26].…”