Maternal vaccination impacts on neonatal susceptibility and response to Bordetella pertussis

Bordetella pertussis (Bp), the causative agent of "whooping cough," is the most important vaccine-preventable disease and an NIH and CDC high priority. The incidence rates of pertussis have increased over recent years, corresponding to the switch from the whole cell pertussis vaccine (wP) priming and acellular pertussis vaccine (aP) boosting vaccination in the early 2000s, to the current aP-only vaccination. Women given the safer but less effective aP vaccines are a rapidly increasing proportion of birthing mothers, creating a complex transition that we poorly understand and that may have particular risks to the most highly sensitive population, newborns. To protect neonates during the months before they can be fully vaccinated the CDC recommends a cocooning strategy, vaccinating all their potential contacts, creating local “herd immunity” to prevent exposure. This strategy is based on the dated and inaccurate belief that aP vaccines that protect against disease also prevent infection/transmission. In fact, there is growing evidence that aP vaccinated individuals, despite significant anti- Bp antibody titers, can still be colonized and can transmit Bp to close contacts, including their babies. Another approach, maternal vaccination where antibodies to Bp are transferred via placenta and colostrum/milk to the newborn, although the actual protective effect of antibody transfer is unknown. In fact, the efficacy of maternally transferred antibodies in protecting against colonization or disease has not been determined clinically. Such a clinical study would be challenging and costly and has not been attempted. The experimental evidence indicates that antibodies alone do little to prevent disease. Therefore, we are effectively in the middle of a nationwide test of the differential effects of wP-primed and aP-primed vaccination of mothers on the protection conferred to their offspring without a complete understanding of the likely impact. To address this urgent knowledge gap, we recently developed a novel mouse neonatal experimental infection system that more accurately models the unique features of the human neonatal immune system, enabling us to probe vaccine-induced protection against Bp transferred from mother to offspring. Our exciting preliminary data demonstrate that both the wP and aP maternal vaccinations confer substantial protection to the offspring’s lungs. These results demonstrate that we can measure the profound effects of maternal vaccination on the protection of pups. This approach allows us the specific means to examine the mechanisms of differentially conferred protection, as proposed below. Here we will utilize a combination of innovative immunological techniques to address the central hypothesis that transferred maternal antibodies contribute to protection in neonates via mechanisms we can distinguish using tools unique to the mouse model.