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.

ABSTRACT

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 µg SARS-CoV-2 recombinant nanoparticle spike protein [rS]; 50 µg 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.