Memory responses seen after whole-cell pertussis (wP) and acellular pertussis (aP) vaccine priming are different and reflect better long-term protection against pertussis disease seen with the whole-cell vaccines. Although acellular vaccines generate higher levels of antigen-specific IgG to the antigens included in the aP vaccines, there are many more pertussis antigens included in whole-cell vaccines. Acellular vaccine priming is associated with skewing of the immune response to a more Th2-like response, whereas whole-cell priming is associated with a Th1/Th17 response. Repeated booster doses of acellular vaccine in children primed with acellular vaccine has been shown to result in progressively shorter duration of protection against disease. This may be explained by the generation of higher levels of antigen-specific IgG4, which does not bind complement and leads to a suboptimal inflammatory response and impaired phagocytosis and antimicrobial defense. In contrast, whole-cell priming followed by aP vaccine boosters results in better opsonization, phagocytosis, and complement mediated killing through the preferential induction of IgG1.