Vaccination is one of the most effective medical interventions. However, optimization of existing as well as design of new vaccines is still mostly conducted empirically; a rational approach to vaccine design is largely prohibited by the lack of insight into the relevant mechanisms underlying immune-mediated protection. To delineate the impact of variables on immune memory formation following vaccination, we took advantage of a trial assessing the role of the age of the recipient and the number of administered doses of the quadrivalent HPV vaccine in a well-characterized longitudinal cohort of girls and young women. We found that age of the recipient and the number of doses administered differentially impact the development of B and T cell memory. Specifically, age of the recipient significantly impacted generation of HPV 18-specific B cell memory, while the number of vaccine doses displayed a significant effect on the development of HPV-specific T cell memory. Our data indicate that rational design of vaccines has to be tailored according to the desired induction of B and/or T cell memory.