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Human papillomavirus (HPV) vaccines provide excellent protection from infection and disease. The minimum number of doses needed for long-term protection and the potential need for boosters are areas of continuing interest. Studies on the durability of vaccines have focused on antibodies, fewer have analyzed memory immune cells that could provide protection even when antibody levels are low. In this study, subjects who had participated in one of two trials comparing two and three doses (2D, 3D), were given an additional vaccine dose (Gardasil®9, 9vHPV) several years after the initial vaccine doses, and the magnitude of immune responses were compared. Both trials had 2D children who received doses at 0 and 6 months (G1a), 3D children 9-13 (08-001) or 9-14 (V503-010) years old at enrollment in the original trial (G2) and 3D women (age 16-26) (G3). Trial V503-010 had a second 2D group of children vaccinated at 0 and 12 months (G1b). Changes in numbers of HPV specific memory B cells (Bmem) (N = 6 per group, both studies) at 1 month and plasmablasts (PB) (08-001: N = 6 per group, V503-010: G1a N = 12, G1b N = 8, G2 N = 6, G3 N = 28) at 1 week, relative to baseline at the additional dose, were compared among groups. Changes in the geometric mean titers (GMTs) of HPV specific antibodies relative to baseline were compared (N = same as PB). Statistically significant (p < 0.05) increases in the numbers of PB, Bmem and antibody levels (GMT) were seen among subjects receiving an extra vaccine dose relative to baseline. Increases in the number of PB and Bmem were not significantly different among subjects receiving two or three doses. Thus, robust immune responses were observed and did not differ significantly among subjects vaccinated with two or three doses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Denise Galloway reports financial support was provided by Merck Sharp and Dohme Pharmaceuticals. Denise Galloway reports a relationship with Merck Sharp and Dohme Pharmaceuticals that includes: consulting or advisory and funding grants. Honoraria paid from Merck to Erin M. Scherer for lectures/seminars delivered, Manish Sadarangani has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer and Sanofi-Pasteur. All funds have been paid to his institute, and he has not received any personal payments. Sandhya Sankaranarayanan, Alain Luxembourg and are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Background: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose., Methods: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined., Results: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays., Conclusions: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)