Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination

Eduardo Lazcano-Ponce, Leticia Torres-Ibarra, Aurelio Cruz-Valdez, Jorge Salmerón, Tonatiuh Barrientos-Gutiérrez, Javier Prado-Galbarro, Margaret Stanley, Nubia Muñoz, Rolando Herrero, Mauricio Hernández-Ávila, Eduardo Lazcano-Ponce, Leticia Torres-Ibarra, Aurelio Cruz-Valdez, Jorge Salmerón, Tonatiuh Barrientos-Gutiérrez, Javier Prado-Galbarro, Margaret Stanley, Nubia Muñoz, Rolando Herrero, Mauricio Hernández-Ávila

Abstract

Background: There are limited data regarding the duration of immunity induced by different human papillomavirus (HPV) vaccination schedules and the immunogenicity of a booster dose of both bivalent HPV vaccine (bHPV) or quadrivalent HPV vaccine (qHPV).

Methods: Follow-up of a nonrandomized clinical trial to evaluate the 5-year antibody persistence of the bHPV in girls (age, 9-10 years) and women (age, 18-24 years). Noninferiority of the 2-dose versus 3-dose schedule among girls was evaluated at months 54 (n = 639) and 64 (n = 990). Girls vaccinated with a 2-dose schedule of bHPV or qHPV received a booster dose of either vaccine at month 61. Immunogenicity was measured using a virus-like particle-based enzyme-linked immunosorbent assay. Geometric mean titers (GMTs) for HPV16/18 were estimated after stratification by vaccination schedule and age group.

Results: At months 54 and 64, the 2-dose schedule remained noninferior to the 3-dose schedule. GMTs remained above natural infection levels across all age groups up to 64 months. After the booster, anti-HPV16/18 GMTs increased exponentially with the same pattern, regardless of vaccine administered. No safety concerns were identified with the booster dose.

Conclusions: A 2-dose schedule is highly immunogenic in girls, suggesting a high immune memory. Thus, a booster dose is likely to be unprofitable, considering the low global immunization coverage.

Clinical trials registration: NCT01717118.

Figures

Figure 1.
Figure 1.
Flow of participants through the study. The difference between the number of adolescents at month 61 and those at month 64 is attributable to a parent’s rejection to the blood specimen collection for serological analysis at month 64. ATP, According to protocol; bHPV, bivalent HPV vaccine; HPV, human papillomavirus; M, month; qHPV, quadrivalent HPV vaccine.
Figure 2.
Figure 2.
Anti–human papillomavirus type 16 (HPV16; A) and anti-HPV18 (B) geometrical mean titers (GMTs) at different study time points, by study group (according-to-protocol cohort). The solid line denotes GMTs for girls who received the 3-dose schedule (M 0,1,6), the reference group for noninferiority analysis. Dashed lines denote GMTs for subjects who cleared natural infection: 29.8 EU/mL (95% confidence interval, 28.5–31.1) for HPV16 and 22.7 EU/mL (95% CI, 21.7–23.7) for HPV18 [20]. The error bars represent 95% CIs. The booster dose was given only to girls who received 2 doses of HPV vaccine (M 0,6) at 9–10 years of age. bHPV, bivalent HPV vaccine; EU, enzyme-linked immunosorbent assay units; M, month; qHPV, quadrivalent HPV vaccine.
Figure 3.
Figure 3.
Proportion of adverse events among girls following a booster dose of bivalent human papillomavirus (HPV) vaccine (bHPV) or quadrivalent HPV vaccine (qHPV) administered 61 months after the first vaccine dose. The error bars represent 95% confidence intervals. There were no reports of paresthesia or erythema in the group of girls previously vaccinated with qHPV who received a booster of bHPV.

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Source: PubMed

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