Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

• Published in: Journal of adolescent health 2012, Vol.50 (1), p.38-46
• Main Authors: Pedersen, Court, M.D., Sc.D, Breindahl, Morten, M.D., Ph.D, Aggarwal, Naresh, M.B.B.S., C.C.F.P., F.C.F.P, Berglund, Johan, M.D., Ph.D, Oroszlán, György, M.D., Ph.D, Silfverdal, Sven Arne, M.D., Ph.D., M.P.H, Szüts, Péter, M.D., Ph.D, O'Mahony, Michael, Ph.D, David, Marie-Pierre, M.Sc, Dobbelaere, Kurt, M.D, Dubin, Gary, M.D, Descamps, Dominique, M.D
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adolescent; ADOLESCENTS; Adverse effects; Aluminum Hydroxide - administration & dosage; Biological and medical sciences; CERVICAL-CANCER VACCINE; Child; CHILDREN; Drug Therapy, Combination; Female; FOLLOW-UP; Girls; Hepatitis A; Hepatitis A vaccines; Hepatitis A Vaccines - administration & dosage; Hepatitis A Vaccines - adverse effects; Hepatitis A Vaccines - immunology; Hepatitis A virus; Hepatitis B; Hepatitis B vaccines; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - adverse effects; Hepatitis B Vaccines - immunology; Hepatitis B virus; HOMOSEXUAL-MEN; Human papillomavirus; Human papillomavirus 16 - drug effects; Human papillomavirus 16 - immunology; Human papillomavirus 18 - drug effects; Human papillomavirus 18 - immunology; Human papillomavirus vaccines; Human papillomaviruses; Human viral diseases; Humans; Immune response; IMMUNIZATION; Immunogenicity; Infectious diseases; Lipid A - administration & dosage; Lipid A - analogs & derivatives; Medical sciences; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - adverse effects; Papillomavirus Vaccines - immunology; PARTICLE VACCINE; Pediatrics; Randomized controlled trial; Safety; SUSTAINED EFFICACY; TYPE-18; Uterine Cervical Neoplasms - prevention & control; Vaccines; Viral diseases; Viral hepatitis; YOUNG-WOMEN
• ISSN: 1054-139X; 1879-1972; 1879-1972
• DOI: 10.1016/j.jadohealth.2011.10.009

Abstract Purpose This randomized, open, controlled, multicenter study (110886/ NCT00578227 ) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone. Methods Healthy girls (9–15 years) were age-stratified (9, 10–12, and 13–15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7. Results The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0–5,080.8] and 5,288.4 [4,713.3–5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0–4,038.4] and 5,646.5 [4,481.3–7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4–26,312.0] and 26,981.9 [23,909.5–30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7–9,826.6] and 11,182.7 [9,924.8–12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population. Conclusions Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9–15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls.