PMID- 38310018 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240226 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 42 IP - 6 DP - 2024 Feb 27 TI - One-year follow-up of the immunogenicity and safety of a primary series of the NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Final report of a phase I/II randomized controlled trial. PG - 1319-1325 LID - S0264-410X(24)00068-9 [pii] LID - 10.1016/j.vaccine.2024.01.056 [doi] AB - BACKGROUND: In the interim report of this phase I/II randomized, placebo-controlled trial in Japanese adults, a two-dose primary series of NVX-CoV2373 (5 microg SARS-CoV-2 recombinant nanoparticle spike protein [rS]; 50 microg Matrix-M) administered 21 days apart induced robust anti-SARS-CoV-2 immune responses up to day 50 and had an acceptable safety profile. METHODS: Following the double-blind phase of this study (day 1-50), participants were informed about their assignment to NVX-CoV2373 or placebo, and their reconsent was required for continuation in the open-label phase (day 51-387). This final report evaluated immunogenicity on days 202 and 387, and safety findings from the 1-year follow-up. RESULTS: In total, 131/150 participants in the NVX-CoV2373 arm and 4/50 in the placebo arm completed the study. The most common reason for discontinuation was because the participant requested a publicly available COVID-19 vaccine. At 6 months and 1 year after the second vaccine dose, both the geometric mean titres of anti-SARS-CoV-2 rS serum immunoglobulin G and serum neutralizing antibodies against the SARS-CoV-2 ancestral strain were numerically higher than before the second dose. There were no deaths, adverse events (AEs) leading to participant withdrawal, or AEs of special interest throughout the trial. During follow-up, 2.0 % (1/50) of participants in the placebo arm reported COVID-19 approximately 1 month after the second vaccine dose (serious AE requiring hospitalisation, already presented in the interim report) and 2.7 % (4/150) in the NVX-CoV2373 arm after approximately 10 months (mild [2/4] or moderate [2/4] in severity). DISCUSSION: A primary series of NVX-CoV2373 induced persistent immune responses up to 1 year after the second dose. The vaccine was well tolerated and had an acceptable safety profile. We believe our findings offer important insights for determining dosing intervals between primary and booster vaccinations. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Kuriyama, Kenji AU - Kuriyama K AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Osaka, Japan. Electronic address: kenji.kuriyama@takeda.com. FAU - Murakami, Kyoko AU - Murakami K AD - Medical Franchise Vaccine, Japan Medical Office, Takeda Pharmaceutical Company Ltd, Tokyo, Japan. Electronic address: kyoko.murakami@takeda.com. FAU - Sugiura, Kenkichi AU - Sugiura K AD - Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Osaka, Japan. Electronic address: kenkichi.sugiura@takeda.com. FAU - Sakui, Sho AU - Sakui S AD - Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Osaka, Japan. Electronic address: sho.sakui@takeda.com. FAU - Schuring, Ron P AU - Schuring RP AD - Clinical Development, Global Vaccine Business Unit, Takeda Pharmaceuticals International AG, Zurich, Switzerland. Electronic address: ron.schuring@takeda.com. FAU - Masuda, Taisei AU - Masuda T AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Osaka, Japan. Electronic address: taisei.masuda@takeda.com. FAU - Mori, Mitsuhiro AU - Mori M AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Osaka, Japan. Electronic address: mitsuhiro.mori@takeda.com. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20240202 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 2SCD8Q63PF (NVX-CoV2373 adjuvated lipid nanoparticle) RN - 0 (COVID-19 Vaccines) RN - 0 (Vaccines) RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) SB - IM MH - Adult MH - Humans MH - *COVID-19 Vaccines/adverse effects MH - Follow-Up Studies MH - Japan MH - *Vaccines MH - Antibodies, Neutralizing MH - SARS-CoV-2 MH - Immunogenicity, Vaccine MH - Antibodies, Viral MH - Double-Blind Method OTO - NOTNLM OT - COVID-19 OT - Immunogenicity OT - Japanese adults OT - NVX-CoV2373 OT - SARS-CoV-2 OT - Safety COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenji Kuriyama reports financial support was provided by Japan Agency for Medical Research and Development. Kenji Kuriyama reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. Kyoko Murakami reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment and equity or stocks. Kenkichi Sugiura reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. Sho Sakui reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. Ron P Schuring reports a relationship with Takeda Pharmaceuticals International AG that includes: employment. Taisei Masuda reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. Mitsuhiro Mori reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. EDAT- 2024/02/04 00:42 MHDA- 2024/02/26 06:43 CRDT- 2024/02/03 22:01 PHST- 2023/05/26 00:00 [received] PHST- 2023/10/17 00:00 [revised] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/02/26 06:43 [medline] PHST- 2024/02/04 00:42 [pubmed] PHST- 2024/02/03 22:01 [entrez] AID - S0264-410X(24)00068-9 [pii] AID - 10.1016/j.vaccine.2024.01.056 [doi] PST - ppublish SO - Vaccine. 2024 Feb 27;42(6):1319-1325. doi: 10.1016/j.vaccine.2024.01.056. Epub 2024 Feb 2.