Exceeding expectations: factors contributing to the potency of human papillomavirus vaccines

The commercial prophylactic vaccines for human papillomavirus (HPV) are subunit vaccines composed of spontaneously assembled virus-like particles formed from 360 copies of the L1 major virion protein. The vaccines have exceeded expectations in immunogenicity, clinical trials efficacy, and effectiveness in national immunisation programmes. Booster doses are not required to generate these outcomes. In this Review, we discuss the immunological and virological considerations that can help with explaining the high potency of HPV vaccines. These considerations provide biological plausibility for HPV vaccines being the first subunit vaccines to confer high-level, long-term protection after a single priming dose, support projections of eliminating vaccine-targeted types in populations with achievable coverage rates in adolescents, and offer insights for developing future antimicrobial vaccines.