Safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine coadministered with quadrivalent influenza vaccine: A phase 3 randomized trial
Affiliation:
1. PMG Research of Wilmington, LLC, 1202 Medical Center Dr, Wilmington, NC 28401, USA;2. Indago Research & Health Center, Inc., 3700 W 12th Ave, Suite 300, Hialeah, FL 33012, USA;3. Vaccine Research and Development, Pfizer Inc, 500 Arcola Rd, Collegeville, PA 19426, USA;4. Vaccine Research and Development, Pfizer Inc, 401 North Middletown Rd, Pearl River, NY 10965, USA;1. National Pingtung University of Science and Technology, Pingtung, Taiwan;2. Kaohsiung Medical University, Kaohsiung, Taiwan;1. Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do 16499, Republic of Korea;2. AI-Superconvergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon, Gyeonggi-do 16499, Republic of Korea;3. Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea;1. Brown University, School of Public Health, USA;2. Rhode Island, Department of Health, USA;1. Environmental Medicine and Population Sciences, Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Japan;2. Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Japan;3. Department of Health Care Administration and Management, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;4. Department of Food Science, Faculty of Home Economics, Otsuma Women''s University, Tokyo, Japan;1. Department of Paediatric Infectious Diseases and Immunology Children''s Health Ireland at Crumlin & Temple Street, Dublin, Ireland;2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;3. School of Medicine, University College Dublin, Dublin, Ireland;4. Children’s Hospital of Philadelphia Global Health Center, USA;5. Niños Primeros en Salud, Consuelo, Dominican Republic;6. Hospital Materno Infantil San Lorenzo de Los Mina, Santo Domingo, Dominican Republic;7. Clinical Innovation Unit, The Rotunda Hospital, Dublin, Ireland;8. Irish Meningitis and Sepsis Reference Laboratory, Children’s Health Ireland at Temple Street, Dublin, Ireland;9. Department of Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland;10. Division of Obstetrics & Gynaecology, The Rotunda Hospital, Dublin, Ireland;11. Division of Pediatric Infectious Diseases, Grossman School of Medicine, New York University, New York, NY, USA;12. Global Medical and Scientific Affairs, Merck Research Laboratories, Merck & Co., Inc, Upper Gwynedd, PA, USA;1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;2. World Organisation for Animal Health Reference Laboratory for Classical Swine Fever, China Institute of Veterinary Drug Control, Beijing 100081, China;3. Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China;4. Laboratory, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430015, China
Abstract:
IntroductionOlder adults are at increased risk of adverse outcomes from pneumococcal disease and influenza infections. Vaccination is an established strategy for preventing both illnesses. This study evaluated coadministration of 20-valent pneumococcal conjugate vaccine (PCV20) and an adjuvanted quadrivalent inactivated influenza vaccine (QIV).MethodsThis phase 3, randomized, double-blind, multicenter study included 1796 US adults ≥ 65 years of age randomized 1:1 to receive either PCV20 and QIV followed 1 month later by saline (Coadministration group) or QIV and saline followed 1 month later by PCV20 (Separate Administration group). Primary immunogenicity objectives were to show noninferiority of PCV20 and QIV coadministration compared with separate administration of either vaccine based on serotype-specific opsonophagocytic activity (OPA) titers for PCV20 and strain-specific hemagglutination inhibition assay (HAI) titers for QIV. Safety endpoints included local reactions, systemic events, and adverse events (AEs).ResultsNoninferiority for pneumococcal and influenza antibody responses (lower bound 95 % CI of the OPA and HAI geometric mean ratios of > 0.5 and > 0.67, respectively) was shown for the Coadministration group compared with the Separate Administration group for all 20 pneumococcal serotypes and all 4 influenza vaccine strains. Local reactions and systemic events were mostly mild or moderate in severity across groups; injection site pain was the most frequent local reaction, and fatigue was the most frequent systemic event. Mild and moderate fatigue were reported more frequently after PCV20 and QIV coadministration compared with separate administration (mild, 20.0 % vs 10.8 %-12.6 %; moderate, 12.3 % vs 8.4 %-9.6 %); this was not considered clinically significant. AE reporting rates were similar across groups, and no serious AEs were considered vaccination-related.ConclusionsImmune responses after coadministration of PCV20 and QIV were noninferior to separate administration of either vaccine. The PCV20 safety profile was similar when given together with or after QIV. These findings support PCV20 and QIV coadministration.Trial Registration: ClinicalTrials.gov, NCT04526574.
