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

• Published in: Vaccine Vol. 42; no. 3; pp. 662 - 670
• Main Authors: Kuriyama, Kenji, Murakami, Kyoko, Sugiura, Kenkichi, Sakui, Sho, Schuring, Ron P., Mori, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 25.01.2024; Elsevier Limited
• Subjects: Adult; Adults; Adverse events; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; Heterologous booster; Humans; IgG antibody; Immune response; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Infections; Japan; Labels; mRNA; mRNA Vaccines; NVX-CoV2373; Robustness; Safety; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccine immunogenicity; Vaccine safety; Vaccines; Japan; United Kingdom > UK; United States > US; LLOQ; rS; SAP; SCR; AE; AESI; CoP; CI; IgG; Vaccine safety; EU/mL; Heterologous booster; nAb; GMT; COVID-19; SARS-CoV-2; GMFR; SAE; MN50; Vaccine immunogenicity; MAAE; NVX-CoV2373; ULOQ; ELISA
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2023.12.036

•This study assessed two NVX-CoV2373 boosters given 5 months apart in Japanese adults.•This is the first assessment of a second NVX-CoV2373 booster in Japanese adults.•The second booster induced more robust immune responses than the first booster.•Neutralizing antibody titres were 1.4-fold higher than after the first booster.•The second booster was well tolerated and had an acceptable safety profile. 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. 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. 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. 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.