title: 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.
authors.affiliation: a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernández-Ávila
authors.affiliation: a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Torres-Ibarra
authors.affiliation: b University of Cambridge ; Cambridge , UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Stanley
authors.affiliation: a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.|c Unidad de Investigación Epidemiológica y en Servicios de Salud; Instituto Mexicano del Seguro Social ; Cuernavaca , Morelos , México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
authors.affiliation: a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cruz-Valdez
authors.affiliation: d National Institute of Cancer ; Bogotá , Colombia.
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.affiliation: e International Agency for Research on Cancer ; Lyon , France.
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: f Centro Nacional para la Salud de la Infancia y la Adolescencia ; Mexico City , Mexico.
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Villaseñor-Ruíz
authors.affiliation: a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lazcano-Ponce
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D062665:Epidemiological Monitoring; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D008800:Mexico; D030361:Papillomavirus Infections / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
keywords: HPV quadrivalent vaccine; Mexico; alternative vaccination scheme; non-inferiority