PMID- 38129286 OWN - NLM STAT- MEDLINE DCOM- 20240212 LR - 20240212 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 42 IP - 3 DP - 2024 Jan 25 TI - Immunogenicity and safety of a second heterologous booster dose of NVX-CoV2373 (TAK-019) in healthy Japanese adults who had previously received a primary series of COVID-19 mRNA vaccine: Interim analysis report of a phase 3 open-label trial. PG - 662-670 LID - S0264-410X(23)01482-2 [pii] LID - 10.1016/j.vaccine.2023.12.036 [doi] AB - BACKGROUND: The phase 3, single-arm, open-label TAK-019-3001 study assessed two heterologous booster doses of NVX-CoV2373 administered 5 months apart in healthy Japanese adults who had completed a primary series of a COVID-19 mRNA vaccine 6-12 months previously. In the main part of this study, a first booster induced rapid and robust anti-SARS-CoV-2 immune responses, addressing waning immunity in participants. METHODS: This interim analysis evaluated the immunogenicity and safety of a second booster in the extension part of this study including comparisons with the first booster. Immunogenicity was assessed on extension day (ED) 1 (before vaccination) and ED15. Solicited and unsolicited adverse events occurring in the 7 and 28 days, respectively, after vaccination were assessed. RESULTS: Of the 150 participants who received a first NVX-CoV2373 booster, 129 were administered a second booster on ED1. Participant characteristics were consistent between the main and extension parts of the study. Titres of anti-SARS-CoV-2 rS serum immunoglobulin G and serum neutralizing antibodies against the SARS-CoV-2 ancestral strain at ED15 were 4.0- and 3.0-fold higher, respectively, than those observed 5 months after the first booster on ED1, and 3.0- and 1.4-fold higher, respectively, than those observed 14 days after the first booster on day 15. The proportions of participants who experienced solicited local and systemic adverse events (AEs) in the 7 days after the second booster were 73.6 % and 51.2 %, respectively: most were of grade 2 severity or lower. Seven percent of participants experienced unsolicited AEs in the 28 days after the second booster: all were unrelated to the treatment. There were no deaths or AEs leading to study discontinuation. DISCUSSION: A second heterologous NVX-CoV2373 booster in healthy Japanese adults induced more robust anti-SARS-CoV-2 immune responses than the first booster. The second booster was well tolerated. No new safety concerns were identified. CI - Copyright (c) 2023 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, Japan Takeda Pharmaceuticals, 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 - Mori, Mitsuhiro AU - Mori M AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan Takeda Pharmaceuticals, Osaka, Japan. Electronic address: mitsuhiro.mori@takeda.com. LA - eng PT - Clinical Trial, Phase III PT - Journal Article DEP - 20231221 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (mRNA Vaccines) RN - 2SCD8Q63PF (NVX-CoV2373 adjuvated lipid nanoparticle) SB - IM MH - Adult MH - Humans MH - Antibodies, Neutralizing MH - Antibodies, Viral MH - *COVID-19/prevention & control MH - *COVID-19 Vaccines/adverse effects MH - Immunogenicity, Vaccine MH - Japan MH - mRNA Vaccines MH - SARS-CoV-2 OTO - NOTNLM OT - COVID-19 OT - Heterologous booster OT - NVX-CoV2373 OT - SARS-CoV-2 OT - Vaccine immunogenicity OT - Vaccine 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 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 Sakai reports a relationship with Takeda Pharmaceutical Company Limited that includes: employment. Mitsuhiro Mori 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. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/12/22 00:42 MHDA- 2024/02/05 06:44 CRDT- 2023/12/21 22:02 PHST- 2023/10/22 00:00 [received] PHST- 2023/12/09 00:00 [accepted] PHST- 2024/02/05 06:44 [medline] PHST- 2023/12/22 00:42 [pubmed] PHST- 2023/12/21 22:02 [entrez] AID - S0264-410X(23)01482-2 [pii] AID - 10.1016/j.vaccine.2023.12.036 [doi] PST - ppublish SO - Vaccine. 2024 Jan 25;42(3):662-670. doi: 10.1016/j.vaccine.2023.12.036. Epub 2023 Dec 21.