Immunogenicity of 2 or 3 Doses of 9vHPV Vaccine in U.S. Female Individuals 15 to 26 Years of Age

Abstract

BACKGROUND: Within the United States, a 9-valent human papillomavirus (9vHPV) vaccine (HPV-6/11/16/18/31/33/45/52/58) is recommended as a two-dose series among individuals 9 to 14 years of age and a three-dose series among those 15 to 26 years of age. Data comparing two versus three doses of 9vHPV vaccine among individuals 15 to 26 years of age are limited. METHODS: We report on an ongoing, single-blinded, randomized noninferiority trial of the 9vHPV vaccine among individuals 15 to 26 years of age in the United States. Participants were randomly assigned to a two-dose (0 and 6 months) or three-dose (0, 2, and 6 months) schedule. Blood draws to assess antibody titers were planned before the first vaccination and at 1 and 6 months after the final vaccination. The primary outcome was the rate of seroconversion at 1 month after final vaccination. The secondary outcome was the two-dose versus three-dose ratio of antibody geometric mean titers (GMTs) for each of the 9vHPV genotypes at 1 and 6 months after final vaccination. This interim analysis reports results of female participants at 1 month after final vaccination. RESULTS: Of 860 participants screened, 438 were enrolled and randomly assigned to the two-dose (n=217) or three-dose (n=221) group. At 1 month after the final vaccine dose, the seroconversion rate for each of the nine HPV genotypes in the vaccine was 100% among participants in the two-dose group and 99% in the three-dose group. The point estimates of the two-dose versus three-dose ratios of antibody GMTs for eight of the nine HPV genotypes were above unity; the ratio for HPV-45 was 0.86 (95% confidence interval [CI], 0.66 to 1.13). This was also the smallest value for the lower bound of the 95% CI for all nine ratios (ratios above 1 favor the two-dose schedule). No serious adverse events were observed. CONCLUSIONS: In this unplanned interim analysis of U.S. female participants 15 to 26 years of age, two doses of 9vHPV vaccine appear to elicit responses similar to three doses at 1 month postvaccination. We await final results at 6 months following the last vaccine dose. (ClinicalTrials.gov number, NCT03943875.)

Figure 1.. Dosing and Sampling Schedule.

Participants were randomly assigned to either a two-dose (0 and 6 months) or three-dose (0, 2, and 6 months) schedule, with V_n indicating vaccine dose number. Gray boxes indicate windows of time during which a participant could return for a follow-up vaccination or blood draw. Blood draws were planned at baseline (B₁), 1 month after final vaccination (B₂), and 6 months after final vaccination (B₃). Given that the timing of the second blood draw (B₂) differed for each participant based upon when they received their final vaccine dose (V₂ or V₃, depending on group), the time windows for these final vaccine administrations and B₂ overlap in the figure. 9vHPV denotes 9-valent human papillomavirus vaccine against human papillomavirus types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Figure 2.. CONSORT (Consolidated Standards of Reporting Trials) Flow Diagram of Participant Population.

mo denotes months.