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.

ABSTRACT

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.