Long-term immunogenicity of alternative HPV vaccine schedules and the effect of an additional dose given three to five years post-primary vaccination

We assessed antibody persistence and the impact of an additional dose administered 42-60 months after initial vaccination. Girls initially vaccinated at ages 9-10 with two doses of quadrivalent HPV vaccine participated in two randomized trials: The 0-6-42HPV study which compared a quadrivalent and bivalent additional dose given at 42 months; The 0-6-60ICI-VPH study compared no additional dose to a quadrivalent dose at 60 months. HPV16/18 antibody detection and geometric mean concentrations (GMCs) were assessed (M9ELISA). Overall, 526 girls provided a blood sample. All had detectable HPV16/18 antibodies 10 years post-initial vaccination. An additional dose at 42 versus 60 months led to similar GMCs, both with higher immune responses compared to 2-dose group participants. Compared to the quadrivalent, the bivalent induced significantly higher HPV18 GMCs, which has unknown clinical significance. Two-dose schedule and delayed quadrivalent or bivalent additional doses are highly immunogenic, supporting long-term immunogenicity of alternative and mixed vaccination schedules.