Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines [DTaP & Tdap] 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 [DTP] and challenged with B. pertussis at 7 mo.
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 [whooping cough] to unvaccinated contacts.
[Acellular pertussis vaccine] which induces an immune response mis-matched to that induced by natural infection, fails to prevent colonization or transmission…
Two common hypotheses for the resurgence have been proposed: i) current acellular pertussis vaccines (aP) vaccines are less effective than the whole-cell pertussis (wP) vaccines they replaced and ii) aP-induced immunity wanes more quickly than anticipated.
[Acellular pertussis] vaccines do not prevent colonization following direct challenge or infection by transmission. In addition, aP-vaccinated animals are capable of transmitting disease to naïve contacts.
At 7 mo of age, vaccinated, naïve, and previously infected (convalescent) animals were challenged with… a B. pertussis clinical isolate that causes severe infection in humans and baboons. Naïve animals were heavily colonized… none of the convalescent animals [with natural immunity] were colonized.
To assess the ability of vaccination to prevent pertussis infection by transmission, two aP-vaccinated animals and one unvaccinated animal were cohoused with a directly challenged, unvaccinated animal.
[A]ll animals became colonized 7–10 d after cohousing with the infected animal. The peak levels and kinetics of colonization were indistinguishable between the naïve and aP-vaccinated animals.
Following challenge, the titers for vaccinated animals were essentially unchanged, whereas boosting was observed for some antigens in convalescent animals.
The resurgence began during the wP vaccine era, but the pace has quickened since aP vaccines were recommended for all primary and booster doses.
[S]everal recent observational studies concluded that children primed with aP vaccine had a twofold to fivefold greater risk of pertussis diagnosis compared with wP-primed children.
[A]nimals vaccinated with wP cleared infection by a direct challenge twice as fast as animals vaccinated with aP. However, neither vaccine was able to prevent colonization as well as immunity from a previous infection.
[R]ecent cohort and case-control studies concluded that 5 [years] following the fifth aP dose, children are fourfold to 15-fold more likely to acquire pertussis compared with within the first year, consistent with waning aP immunity.
We hypothesized an additional explanation for pertussis resurgence is that aP-vaccinated individuals can act as asymptomatic or mildly symptomatic carriers and contribute significantly to transmission in the population.
Observational studies suggest that asymptomatic pertussis can occur in vaccinated children and adults…
However, during the aP vaccine trials, participants were not screened for B. pertussis infection unless they presented with pertussis-like symptoms and at least 7–21 d cough.
In the present study we show that aP-vaccinated primates were heavily infected following direct challenge, and the time to clearance was not different compared with naïve animals.
Similarly, there was no difference in the kinetics or peak level of colonization between aP-vaccinated and naïve animals that were infected by natural transmission.
Importantly, we also show in two experiments that aP-vaccinated animals transmitted B. pertussis to naïve cage mates.
Together these data form the key finding of this study: aP vaccines do not prevent infection or transmission of Bordetella pertussis even 1 mo after completing the primary vaccination series.
[T]he inability to prevent infection was not due to low-antibody titers.
The mechanism by which aP prevents coughing despite heavy bacterial colonization is not known but deserves further attention.
Currently, a major focus of public health agencies is the prevention of pertussis infection in young infants…
One recommendation to reduce transmission of pertussis to infants is by “cocooning,” or vaccinating people who have contact with infants.
Our data show that aP-vaccinated animals are infected and transmit pertussis to naïve contacts. Consistent with these findings, seroepidemiological studies have concluded that B. pertussis circulation is still high in countries with excellent aP uptake, and a cross-sectional study showed that postpartum aP vaccination of mothers did not reduce pertussis illness in young infants.
These data suggest that cocooning is unlikely to be an effective strategy to reduce the burden of pertussis in infants.