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

BackgroundThe 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. MethodsThis 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. ResultsOf 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. DiscussionA 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.