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

JM Warfel, LI Zimmerman… - Proceedings of the …, 2014 - National Acad Sciences
JM Warfel, LI Zimmerman, TJ Merkel
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
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 …
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 naļve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naļve 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.
National Acad Sciences