Evaluation of the immunogenicity of the quadrivalent HPV vaccine using 2 versus 3 doses at month 21: An epidemiological surveillance mechanism for alternate vaccination schemes

Abstract

The cost of HPV vaccines and the need for 3 doses remains a barrier for their inclusion in routine vaccination schedules for girls in low and middle income countries. In a non-inferiority study, we aimed to compare the immunogenicity of a standard 3 doses and a 2 doses schedule. We enrolled 450 participants in an open-label non-randomized clinical trial to evaluate the immunogenicity induced at different ages by the licensed HPV6/11/16/18 quadrivalent vaccine in a 2 doses schedule (0-6 months, n = 150 girls aged 9-10 y) and 3 doses schedule (0, 2, and 6 months; n = 150 girls aged 9-10 y and n=150 women aged 18 to 24 years). To assess the antibody response, blood samples were obtained at Month 7 and 21 after the first vaccination from participants in all study groups. cLIA testing was performed at Merck Research Laboratories. Antibody levels were expressed as milli-Merck units (mMU) per ml. Primary outcome was non-inferiority (95% CI, lower bound >0.5) of the geometric mean titers (GMT) ratios for HPV6, HPV11, HPV16 and HPV18 antibodies 7 and 21 months after the first dose among girls receiving 2 doses compared with young women and girls receiving 3 doses. All vaccinees were seropositive for both HPV16 and HPV18 antibodies at month 7. At month 21, 98.5 and 56.6% of women 18-24 y old were seropositive for HPV16 and 18, respectively. For girls in the three doses group, seropositivity rates were 99.3 and 86.3% for HPV16 and 18, respectively. For girls in the two doses group rates were 99.3 and 70.2% for HPV16 and 18, respectively. The two doses schedule was non-inferior compared to the 3 doses schedule in same-age girls and to the group of adult women after 21 months of the first vaccine dose. Our results are in agreement with similar trials evaluating the immune response of a 2 doses schedule of both HPV vaccines, supporting the recent WHO recommendation as well as the Mexican policy to incorporate the 2 doses schedule for girls aged 9-11 y.

Keywords: HPV quadrivalent vaccine; Mexico; alternative vaccination scheme; non-inferiority.

Figure 1.

CONSORT diagram. Figure legend. Flowchart of participants disposition throughout the study.

Figure 2.

Kinetics of antibody responses to HPV-16/18/6/11 from quadrivalent vaccine. *GMTs, geometric mean titers; milli-Merck units per mL (mMU/mL); CI, confidence interval; M 0,2,6, HPV-16/18/6/11 vaccine at standard schedule at 0,2,6 months; M 0–6–60, HPV-16/18/6/11 vaccine at extended schedule at 0–6–60 months. Plateau (dotted line), GMT values for Canadian women ages 16–26 y who were vaccinated with 3 doses of the quadrivalent vaccine.