Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis

Abstract

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in wholecell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection. Whooping cough is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis (1). In the prevaccine era, pertussis was rampant in the United States with annual reported cases ranging from 150,000 to 250,000 per year and with fatality rates approaching 10% (2). The introduction of combination diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccines in the 1940s and a gradual increase in vaccine coverage led to a dramatic decrease in pertussis incidence with a nadir of 1,000 cases reported in 1976. Due to concerns over the reactogenicity of the whole-cell pertussis vaccine and the prospects of diminishing acceptance among parents, combination diphtheria, tetanus, and acellular pertussis (DTaP) vaccines were introduced in the United States in 1991 and replaced whole-cell vaccines for all pertussis vaccinations in 1997. Currently acellular vaccines are the only pertussis vaccines licensed in the United States and much of the developed world (3). However, despite 95% vaccine coverage in infants, the annual number of reported pertussis cases has been rising over the last 20 to 30 years in the United States (4, 5). The rate of pertussis resurgence increased dramatically following the introduction of acellular vac...

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

“…Besides the previous documented differential Th1 versus Th2 polarization (43), we show a differential IL-9/IL-17 polarization in adulthood after aP versus wP childhood vaccination. Indeed, stronger IL-17 polarization from wP vaccination has been reported to be associated with higher protection in baboon models (15,26,27,44) and to be pivotal in the mediation of adaptive immunity by tissue-resident memory T cells after natural infection in mice (45,66). Although IL-17 has been detected in supernatants of PBMCs stimulated with pertussis antigens (67,68), to the best of our knowledge, this is the first time that CD4 + T cells secreting both IL-9 and IL-17 have been shown to be associated with pertussis-specific responses after wP or aP vaccination regimens in humans.…”

“…Overall, these data highlight a persistent polarization of T cell responses in adulthood decades after priming and despite continued aP boosting of both cohorts (from 1996 onward as part of the recommend immunization schedule). The much stronger IL-17 polarization was reported as being associated with protection and wP vaccination in mouse and baboon models, but had not been shown for humans (15,26,27,(44)(45)(46).…”

Circulating follicular T helper cells and cytokine profile in humans following vaccination with the rVSV-ZEBOV Ebola vaccine

“…Until recently, these cells had been associated predominantly with disease progression and pathology, but it is now increasingly understood that they play a crucial role in mediating protection against a variety of pathogens232425 and that they may be induced mainly by live, attenuated vaccines2326 and mucosal vaccines27. Both Tfh2 and Tfh17 subsets have been shown to be efficient in providing B cell help20.…”

Pre-clinical study of protective potency of candidate recombinant live pertussis vaccine for intranasal administration

“…Этот результат совпадает с результатами тестирования бактериальной нагрузки в носоглотке вакцинированных ЦКВ павианов анубис после их экспериментального заражения вирулентными бактериями возбудителя коклюша. В работе [16] продемонстрирована ускоренная по отношению к невакцинированным животным элиминация бактерий у обезьян, инъекционно вакцинированных ЦКВ.…”