Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination

Abstract

Background: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women.

Methods: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women.

Results: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination.

Conclusion: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Keywords: Human papillomavirus; Natural immunity; Single dose; Vaccine immune responses; quadrivalent HPV vaccine.

Fig. 1

Evolution of immune responses for vaccine-targeted HPV types 16, 18, 6 and 11 obtained using M9ELISA assay over time in the recipients of a single-dose or three doses of the HPV vaccine compared to the antibody levels detected in unvaccinated participants (natural immunity) [*blood was collected from three dose recipients at 7 months and from single dose recipients at 12 months after dose 1].

Fig. 2

Evolution of neutralization geometric mean titres for HPV 16, 18, and 11 obtained using PBNA assay over time in the recipients of a single-dose, two or three doses of the HPV vaccine compared to the antibody levels detected in unvaccinated participants (natural immunity) [*blood was collected from single dose recipients at 24 months and from two/three dose recipients at 36 months after dose 1. HPV 11 neutralization titres were tested at months 60 and 120 time points only].