Pertussis still represents a major cause of morbidity and mortality worldwide. Although vaccination is the most powerful tool in preventing pertussis and despite nearly 70 years of universal childhood vaccination, incidence of the disease has been rising in the last two decades in countries with high vaccination coverage. Two types of vaccines are commercially available against pertussis: whole-cell pertussis vaccines (wPVs) introduced in the 1940s and still in use especially in low and middle-income countries; less reactogenic acellular pertussis vaccines (aPVs), licensed since the mid-1990s.

In the last years, studies on pertussis vaccination have highlighted significant gaps and major differences between the two types of vaccines in the induction of protective anti-pertussis immunity in humans. This chapter will discuss the responses of the immune system to wPVs and aPVs, with the aim to enlighten critical points needing further efforts to reach a good level of protection in vaccinated individuals.