Immune responses after 2 versus 3 doses of hpv vaccination up to 41/2 years after vaccination: an observational study among Dutch routinely vaccinated girls

Abstract

Background. In 2014 the Netherlands switched from 3 to 2 doses for routine vaccination with the prophylactic bivalent human papillomavirus (HPV) vaccine. The current study explored whether antibody responses are noninferior after 2 versus 3 doses in girls. Methods. Girls vaccinated at 12 years of age with 2 (at 0 and 6 months) or 3 doses (at 0, 1, and 6 months) of the bivalent HPV vaccine were identified in the vaccination registration system. Type-specific antibody concentrations and avidity against HPV-16/18/31/33/45/52/58 were assessed. Analyses were stratified for time since the first dose (0-2, 2-3, 3-4, or 4-41/2 years). Noninferiority (margin, 0.5) of the 2- versus the 3-dose schedule in girls was examined. Results. Geometric mean concentrations (GMCs) for vaccine types were only noninferior for 2 versus 3 doses for HPV-18 (at 2-3 years after the first dose; GMC ratio, 0.89; 95% confidence interval, .57-1.38) For vaccine types and cross-protective types (HPV- 16/18/31/33/45), the avidity index was noninferior for the 2-dose compared with the 3-dose schedule, except for HPV-31 at 4-41/2 years after the first dose and HPV-33 at 3-4 and 4-41/2 years. Conclusions. GMCs for HPV-16/18 were not noninferior for 2 versus 3 doses, except for HPV-18 (at 2-3 years after first dose). However, antibody avidity for these types showed noninferiority, independent of concentrations.