Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033)
Affiliation:
1. Taniguchi Hospital, Osaka, Japan;2. Aiwa Hospital, Saitama, Japan;3. Fukui-ken Saiseikai Hospital, Fukui, Japan;4. Sotobo Children''s Clinic, Chiba, Japan;5. Kyoritsu Narashinodai Hospital, Chiba, Japan;6. Clinical Research, Japan Development, MSD K.K., Tokyo, Japan;7. Biostatistics and Research Decision Sciences, Japan Development, MSD K.K., Tokyo, Japan;1. Transport and Road Safety (TARS) Research Centre, School of Aviation, University of New South Wales, Australia;2. Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia;3. Institute of Statistical Research and Training, University of Dhaka, Dhaka, Bangladesh;4. Child Health Research Foundation, Dhaka, Bangladesh;5. Department of Sociology, University of Dhaka, Dhaka, Bangladesh;6. School of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia;7. Department of Biostatistics, University of Washington, Seattle, WA, United States;8. Global Health Workforce Network (GHWN), World Health Organization, Geneva, Switzerland;9. School of Mathematics, Physics, and Computing, University of Southern Queensland, Toowoomba, Queensland, Australia;1. College of Medicine, University of Florida, Gainesville, FL, USA;2. Department of Orthopaedic Surgery and Sports Medicine, University of Florida, Gainesville, FL, USA;1. School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;2. Institute of Immunology, Third Military Medical University, Chongqing 400038, China;3. Cancer Center, Daping Hospital & Army Medical Center of PLA, Third Military Medical University, Chongqing 400042, China;4. Guangdong Provincial Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China;5. Dermatology Hospital, Southern Medical University, Guangzhou 510091, China;1. Institute for HIV/AIDS and STD Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing, China;2. Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China;1. Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA;2. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;3. Acuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada;1. Global Health Research Center, Duke Kunshan University, Kunshan, Jiangsu, China;2. MindRank Ltd., Hangzhou, China;3. Yinzhou District Disease Prevention and Control Center, Ningbo, Zhejiang, China;4. Indiana State University, IN, USA;5. School of Public Health, Wuhan University, Wuhan, Hubei, China;6. China Center for Health Development Studies, Peking University, Beijing, China;7. PKU Institute for Global Health and Development, Peking University, Beijing, China;8. Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, Zhejiang, China
Abstract:
BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F.MethodsHealthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2–6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3.ResultsOverall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13 shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > −10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI −10.6).ConclusionIn Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series.Trial registration: ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.
