Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Abstract

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.whooping cough | T-cell memory | animal models | adaptive immunity |

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

“…Although the basis of this is still not fully clear, resurgence of pertussis is prominent in countries using acellular pertussis (aP) vaccines. It is becoming more evident that aP vaccines do not induce long lasting protection [1] and studies in animal models have suggested that aP vaccination fails to prevent nasal colonization and transmission of B. pertussis [2]. Studies in a baboon challenge model showed that immunization with an alum-formulated aP vaccine protected animals from disease, but did not prevent nasal colonization or bacterial transmission to naïve animals; nasal colonization in these animals lasted at least as long as that in unvaccinated controls [2].…”

“…It is becoming more evident that aP vaccines do not induce long lasting protection [1] and studies in animal models have suggested that aP vaccination fails to prevent nasal colonization and transmission of B. pertussis [2]. Studies in a baboon challenge model showed that immunization with an alum-formulated aP vaccine protected animals from disease, but did not prevent nasal colonization or bacterial transmission to naïve animals; nasal colonization in these animals lasted at least as long as that in unvaccinated controls [2]. In contrast, baboons immunized with wP vaccine cleared the bacteria faster, whereas previously infected animals were completely protected, with no nasal colonization detected after re-challenge.…”

Experience and challenges on influenza and pertussis vaccination in pregnant women

“…46 Furthermore, immunity induced by whole-cell vaccine also protects against mucosal infection, hence possibly limiting or interrupting transmission of Bordetella pertussis , an effect which is not observed following aP vaccination in baboon model challenge studies. 47 Nevertheless, concern regarding the reactogenicity of whole-cell pertussis vaccine, has resulted in most high-income and some low-middle income countries transitioning to aP vaccines. The increase in frequency and magnitude of current pertussis outbreaks might also be due to changes in lower threshold for investigating and the use of more sensitive molecular diagnostic tool compared to traditional culture methods.…”

The role ofB. pertussisvaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development

“…Both types of vaccines protect the individual against disease but animals vaccinated with ACV were colonized to a higher level and for longer when subsequently challenged with B. pertussis, compared to animals vaccinated with WCV. 7 Interestingly, vaccine-induced immunity, either from WCV or ACV, was inferior to immunity arising from natural infection in terms of protecting against colonisation following subsequent challenge. 7 Thus, it is very likely that the switch to the use of an ACV has changed the epidemiology of pertussis, resulting in the changing disease patterns observed.…”

“…7 Interestingly, vaccine-induced immunity, either from WCV or ACV, was inferior to immunity arising from natural infection in terms of protecting against colonisation following subsequent challenge. 7 Thus, it is very likely that the switch to the use of an ACV has changed the epidemiology of pertussis, resulting in the changing disease patterns observed.…”