Immune responses after two- versus three-doses of HPV vaccination up to 4½ years post vaccination: an observational study among Dutch routinely vaccinated girls (HPV2D)

BACKGROUND: In 2014 the Netherlands switched from three- to two-doses for routine vaccination with the prophylactic bivalent human papillomavirus (HPV)-vaccine. This study explored whether antibody responses are non-inferior after two- compared to three-doses in girls. METHODS: Girls vaccinated at twelve years of age with two-(0,6 months) or three-doses (0,1,6 months) of the bivalent HPV vaccine were identified in the vaccination registration system. Type-specific antibody concentrations and avidity against HPV16/18/31/33/45/52/58 were assessed. Analyses were stratified for time since first dose (0-2, 2-3, 3-4 and 4-4 ½ years). Non-inferiority (margin 0.5) of the two- compared to three-dose schedule in girls was examined. RESULTS: Geometric mean concentrations (GMCs) for vaccine types were only non-inferior for two- compared with three-doses for HPV18 (at 2-3 years after first dose, GMC ratio 0.89, 95%CI 0.57-1.38) For vaccine types and cross-protective types (HPV16/18/31/33/45), avidity index (AI) was non-inferior for the two- compared with three-dose schedule, except for HPV31 at 4-4 ½ years and HPV33 3-4 and 4- 4 ½ years after first dose. CONCLUSION: GMCs for HPV 16/18 were not non-inferior for two- compared to three- doses, except for HPV18 (at 2-3 years after first dose). However, antibody avidity for these types showed non-inferiority, independent of concentrations.