PMID- 34489128 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20220531 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 39 IP - 43 DP - 2021 Oct 15 TI - Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged >/=50 years: A randomized phase III trial (PNEU-PATH). PG - 6422-6436 LID - S0264-410X(21)01071-9 [pii] LID - 10.1016/j.vaccine.2021.08.038 [doi] AB - BACKGROUND: Streptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries. METHODS: This phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged >/=50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23. RESULTS: The most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F). CONCLUSION: Administration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged >/=50 years. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Song, Joon-Young AU - Song JY AD - Korea University College of Medicine, Seoul, South Korea. FAU - Chang, Chih-Jen AU - Chang CJ AD - National Cheng Kung University, Tainan, Taiwan. FAU - Andrews, Charles AU - Andrews C AD - Diagnostics Research Group, San Antonio, TX, USA. FAU - Diez-Domingo, Javier AU - Diez-Domingo J AD - FISABIO, Valencia, Spain. FAU - Oh, Myoung-Don AU - Oh MD AD - Seoul National University College of Medicine, Seoul, South Korea. FAU - Dagan, Ron AU - Dagan R AD - Ben-Gurion University, Beer-Sheva, Israel. FAU - Hartzel, Jonathan AU - Hartzel J AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Pedley, Alison AU - Pedley A AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Li, Jianing AU - Li J AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Sterling, Tina AU - Sterling T AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Tamms, Gretchen AU - Tamms G AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Chiarappa, Joseph A AU - Chiarappa JA AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Lutkiewicz, Jeannine AU - Lutkiewicz J AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Musey, Luwy AU - Musey L AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Tu, Yingmei AU - Tu Y AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: ying.mei.tu@merck.com. FAU - Buchwald, Ulrike K AU - Buchwald UK AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: ubuchwa1@jhmi.edu. CN - V114-016 (PNEU-PATH) study group LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210904 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (23-valent pneumococcal capsular polysaccharide vaccine) RN - 0 (Antibodies, Bacterial) RN - 0 (Pneumococcal Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM MH - Aged MH - *Antibodies, Bacterial MH - Double-Blind Method MH - Humans MH - Immunogenicity, Vaccine MH - Middle Aged MH - *Pneumococcal Infections/prevention & control MH - Pneumococcal Vaccines/adverse effects MH - Vaccination MH - Vaccines, Conjugate/adverse effects OTO - NOTNLM OT - Immunogenicity OT - Pneumococcal conjugate vaccine OT - Pneumococcal disease OT - Safety OT - Sequential vaccination COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JH, AP, JL, TS, GT, JAC, J. Lutkiewicz, LM, YT, and UKB are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. JD-D received grants/research support from MSD, GSK, Sanofi Pasteur, has served on advisory boards of GSK and Johnson & Johnson, and has been a consultant for MSD. JYS and CPA received grants/research support from MSD. MO, CJC, and RD have no conflict of interest. EDAT- 2021/09/08 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/09/07 06:12 PHST- 2021/05/20 00:00 [received] PHST- 2021/08/06 00:00 [revised] PHST- 2021/08/10 00:00 [accepted] PHST- 2021/09/08 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/09/07 06:12 [entrez] AID - S0264-410X(21)01071-9 [pii] AID - 10.1016/j.vaccine.2021.08.038 [doi] PST - ppublish SO - Vaccine. 2021 Oct 15;39(43):6422-6436. doi: 10.1016/j.vaccine.2021.08.038. Epub 2021 Sep 4.