Immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent and one dose of bivalent HPV vaccine versus two doses of nonavalent vaccine – A randomized clinical trial |
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| Institution: | 1. Quebec Public Health Institute, Quebec, Canada;2. Laval University Research Hospital Center, Quebec, Canada;3. Centers for Disease Control and Prevention, Atlanta, USA;1. Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica;2. International Agency for Research on Cancer, Lyon, France;3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA;4. University of California, San Francisco (UCSF), San Francisco, CA, USA;5. Information Management Services (IMS), Calverton, MD, USA;6. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA;7. Department of Pathology, University of Virginia, Charlottesville, VA, USA;8. DDL Diagnostic Laboratory, Rijswijk, The Netherlands;1. Guangxi Center for Disease Control and Prevention, #18 Jin Zhou Road, Nanning 530028, Guangxi, PR China;2. Wuzhou Center for Disease Control and Prevention, #3 Chun Hu Road, Wuzhou 543002, Guangxi, PR China;3. MSD R&D (China) Co., Ltd., #21 Rong Da Road, Beijing 100012, PR China;1. Sasaki Foundation Kyoundo Hospital, 1-8 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan;2. Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0004, Japan;3. Toranomon Womens Clinic, Dai 2 Makoto Bld. 3F, Toranomon, Minato-ku, Tokyo, 105-0001, Japan;4. Hamada Hospital, 2-5 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan;5. Nagoya Teishin Hospital, 1-22-9-2901 Uchiyama, Chikusa, Nagoya, 464-0075, Japan;6. Kobari General Hospital, 29-1 Yokouchi, Noda-shi, Chiba, 278-8501, Japan;7. Chayamachi Ladies Clinic, 2-19 Chayamachi, Kita-ku, Osaka-shi, Osaka, 530-0013, Japan;8. MSD KK, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan;1. Clinical Vaccine Unit and Primary Care Research Consortium, Duke University School of Medicine, 2608 Erwin Road Suite 210, Durham, NC 27705, USA;2. Division of STD Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329-4027, USA;3. Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329-4027, USA;1. Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP, L’Hospitalet de Llobregat, Catalonia, Spain;2. Center for Infection Research in Cancer (CIRC) at Moffitt Cancer Center, Tampa, FL, USA;3. Icahn School of Medicine at Mount Sinai, New York, NY, USA;4. Research Unit, Pablo Tobon Uribe Hospital Medellin, Medellín, Colombia;5. Department of Gynaecology and Obstetrics, Odense University Hospital, Odense, Denmark;6. Department of Medicine, University of California San Francisco, San Francisco, CA, USA;7. Merck & Co., Inc., Kenilworth, NJ, USA;1. National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, Bethesda, MD 20892, United States;2. GlaxoSmithKline Vaccines, Avenue Fleming 20, B-1300 Wavre, Belgium;3. GlaxoSmithKline SA, 2301 Renaissance 22 Boulevard, RN0220, King of Prussia, PA 19406, United States;4. Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Solarium Bldg., Liberia, Costa Rica |
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| Abstract: | BackgroundLimited data is available on the use of different HPV vaccines in the same subjects. We evaluated the immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent (9vHPV) and one dose of bivalent vaccine (2vHPV) administered in different order versus two doses of 9vHPV vaccine.Methods371 girls and boys aged 9–10 years were randomized (1:1) to receive (I) two doses of 9vHPV or (II) a mixed schedule of 2vHPV + 9vHPV or 9vHPV + 2vHPV with a 6 month interval. Antibodies to HPV were tested by ELISA in blood samples collected one or six months post-first dose and one month post-second dose.ResultsPost-first dose of 9vHPV 99.4–100% of subjects were seropositive to 9 HPV types included in the vaccine. GMTs varied from 5.0 to 73.6 IU(AU)/ml depending on HPV type. Post-first dose of 2vHPV all subjects were seropositive to HPV16 and 18 (GMTs 16.7 and 11.7 IU/ml, respectively) and 50.0–76.7% were seropositive to 7 types not included in 2vHPV (GMTs varied from 0.3 to 17.5 AU/ml depending on type). Post-second dose all subjects, regardless of the study group, were seropositive to 9 HPV types included in 9vHPV. Anti-HPV16 and 18 GMTs were higher in subjects with the mixed schedule and for the other 7 HPV types higher in subjects who received two doses of 9vHPV vaccine. A higher proportion of subjects who received 2vHPV reported local or systemic adverse events than those who received 9vHPV as the first dose. Post-second dose there were no differences in reported adverse events between the two vaccines.ConclusionsThe results show the mixed HPV vaccination schedules used in this study are immunogenic and have an acceptable safety profile. Although the seroprotective threshold of antibodies remains unknown the 100% seropositivity to all 9 HPV types included in 9vHPV and the increase of GMTs observed in all study groups post-second dose administration are reassuring and suggest protection might be achieved regardless of the schedule used.Clinical Trials Registration: Clinicaltrials.gov NCT02567955. |
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| Keywords: | Human papillomavirus (HPV) Bivalent vaccine Nonavalent vaccine Mixed schedule |
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