PMID- 34315611 OWN - NLM STAT- MEDLINE DCOM- 20211022 LR - 20220531 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 39 IP - 38 DP - 2021 Sep 7 TI - A phase 3, randomized, double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age. PG - 5428-5435 LID - S0264-410X(21)00863-X [pii] LID - 10.1016/j.vaccine.2021.07.004 [doi] AB - INTRODUCTION: Introduction of pneumococcal conjugate vaccines (PCVs), including the 13-valent PCV (PCV13), has considerably reduced pneumococcal disease burden. However, additional serotypes not in PCV13 continue to present a substantial disease burden. The 20-valent PCV (PCV20) was developed to expand protection against pneumococcal disease beyond PCV13. As part of the phase 3 clinical development program, the current study assessed consistency of immune responses across 3 lots of PCV20 and described the safety profile of PCV20. METHODS: This phase 3, randomized, multicenter, double-blind study of pneumococcal vaccine-naive adults 18-49 years of age randomized 1710 participants in a 2:2:2:1 ratio to receive 1 of 3 lots of PCV20 or PCV13. Immunogenicity was assessed through serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month (28-42 days) after vaccination. Reported local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 30 days, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination were evaluated. RESULTS: Equivalence in immune responses (OPA geometric mean titers) for all 20 vaccine serotypes was demonstrated across the 3 PCV20 lots. Robust responses, assessed by OPA geometric mean fold rises, percentage of participants achieving >/=4-fold rises, and percentage of participants with OPA titers >/=lower limit of quantitation, were observed after PCV20. Reported rates of local reactions, systemic events, and AEs were similar between the pooled PCV20 lots and PCV13; most events were mild or moderate. Reported rates of SAEs and NDCMCs were low and similar between the PCV20 and PCV13 groups. CONCLUSIONS: Three different lots of PCV20 demonstrated robust and consistent immunogenicity. The safety and tolerability of PCV20 was acceptable and similar to that of PCV13. (Clinicaltrials.gov: NCT03828617). CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Klein, Nicola P AU - Klein NP AD - Kaiser Permanente Vaccine Study Center, Oakland, CA 94612, USA. Electronic address: Nicola.Klein@kp.org. FAU - Peyrani, Paula AU - Peyrani P AD - Vaccine Medical Development and Scientific/Clinical Affairs, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: Paula.Peyrani@pfizer.com. FAU - Yacisin, Kari AU - Yacisin K AD - Vaccine Research and Development, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: Kari.Yacisin@pfizer.com. FAU - Caldwell, Nicole AU - Caldwell N AD - Vaccine Research and Development, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: Nicole.Caldwell@pfizer.com. FAU - Xu, Xia AU - Xu X AD - Vaccine Research and Development, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: Xia.Xu3@pfizer.com. FAU - Scully, Ingrid L AU - Scully IL AD - Vaccine Research and Development, Pfizer Inc, Pearl River, NY 10965, USA. Electronic address: Ingrid.Scully@pfizer.com. FAU - Scott, Daniel A AU - Scott DA AD - Vaccine Research and Development, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: Dan.Scott@pfizer.com. FAU - Jansen, Kathrin U AU - Jansen KU AD - Vaccine Research and Development, Pfizer Inc, Pearl River, NY 10965, USA. Electronic address: Kathrin.Jansen@pfizer.com. FAU - Gruber, William C AU - Gruber WC AD - Vaccine Research and Development, Pfizer Inc, Pearl River, NY 10965, USA. Electronic address: bill.gruber@pfizer.com. FAU - Watson, Wendy AU - Watson W AD - Vaccine Research and Development, Pfizer Inc, Collegeville, PA 19426, USA. Electronic address: wendy.watson2@pfizer.com. LA - eng SI - ClinicalTrials.gov/NCT03828617 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210724 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Bacterial) RN - 0 (Pneumococcal Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM MH - Adolescent MH - Adult MH - Antibodies, Bacterial MH - Double-Blind Method MH - Humans MH - Middle Aged MH - *Pneumococcal Infections/prevention & control MH - *Pneumococcal Vaccines/adverse effects MH - Vaccines, Conjugate/adverse effects MH - Young Adult OTO - NOTNLM OT - 20-valent pneumococcal conjugate vaccine OT - Clinical trial OT - Immunogenicity and safety OT - Lot consistency OT - Streptococcus pneumoniae COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PP, KY, NC, XX, IS, DS, KJ, WG, and WW are employees of Pfizer and may hold stock or stock options. NK received research support from Pfizer for this study and research support from Pfizer, GSK, Merck, Sanofi Pasteur and Protein Science (now Sanofi Pasteur) for unrelated studies. EDAT- 2021/07/29 06:00 MHDA- 2021/10/27 06:00 CRDT- 2021/07/28 05:41 PHST- 2021/04/06 00:00 [received] PHST- 2021/07/02 00:00 [revised] PHST- 2021/07/05 00:00 [accepted] PHST- 2021/07/29 06:00 [pubmed] PHST- 2021/10/27 06:00 [medline] PHST- 2021/07/28 05:41 [entrez] AID - S0264-410X(21)00863-X [pii] AID - 10.1016/j.vaccine.2021.07.004 [doi] PST - ppublish SO - Vaccine. 2021 Sep 7;39(38):5428-5435. doi: 10.1016/j.vaccine.2021.07.004. Epub 2021 Jul 24.