Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, Chadwick DR, Clark R, Cosgrove CA, Galloway J, Goodman AL, Heer A, Higham A, Iyengar S, Jeanes C, Kalra PA, Kyriakidou C, Bradley JM, Munthali C, Minassian AM, McGill F, Moore P, Munsoor I, Nicholls H, Osanlou O, Packham J, Pretswell CH, San Francisco Ramos A, Saralaya D, Sheridan RP, Smith R, Soiza RL, Swift PA, Thomson EC, Turner J, Viljoen ME, Fries L, Cho I, McKnight I, Glenn G, Rivers EJ, Robertson A, Alves K, Smith K, and Toback S
Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported., Methods: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses., Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups., Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated., Clinical Trials Registration: EudraCT, 2020-004123-16., Competing Interests: Potential conflicts of interest. K. A., I. C., L. F., G. G., I. Mc., E. J. R., A. R., K. S., and S. T. are employees of Novavax Inc and receive a salary for their work. K. S. reports stock received as part of employment compensation from Novavax. A. R. reports stock or stock options from Novavax. E. J. R. and I. Mc. report Novavax stock. K. A. reports vested and unvested Novavax stock/restricted stock units. I. C. reports Novavax stock and stock options and salary and bonus as an employee of Novavax. L. F. reports consulting fees as a prior full-time employee, now contractor to, Novavax reimbursed hourly for work performed on this study and in analyses and drafting this report, and shares and stock options from Novavax. G. G. reports stock-related compensations from Novavax. S. T. reports royalties or licenses, salary and stock, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, as an employee of Novavax. Guy's and St Thomas' National Health Service (NHS) Foundation Trust (with which A. L. G. is affiliated) received funding from Novavax for this trial. Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. A. L. G. is named as an inventor on a patent covering use of a particular promoter construct that is often used in vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine, and may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the university's revenue sharing policy. M. B. reports a research grant to institution from Novavax related to this manuscript, advisory/speaker fees or grants to the institution from GSK, ViiV, Gilead, Janssen, Moderna, Pfizer, Valneva, MSD, Roche, Cipla, and Mylan and support for attending the online World AIDS conference from ViiV. D. R. C. reports a research grant to institution from Gilead Sciences, unpaid participation as an Independent Data Monitoring Board (IDMB) member for the FLARE Trial, and unpaid role as a British HIV Association trustee member. J. G. reports a research contract with institution from Novavax. C. A. C. reports a research grant to institution from Novavax related to this manuscript, and a research grant to institution from Moderna. P. T. H. reports a research grant to institution from Novavax related to this manuscript, research grants to institution from Pfizer, AstraZeneca, Moderna, Valneva, and Janssen, and payment to institution for educational events from Novavax. P. A. K. reports a research grant to institution from Novavax related to this manuscript, grants or contracts unrelated to this work from Vifor, Astellas, Evotec, Pharmacosmos, and Unicyte; consulting fees from AstraZeneca, Vifor, Unicyte, and UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Vifor, AstraZeneca, Pfizer, Pharmacosmos, Napp, and Bayer; and support for attending meetings and/or travel from Pharmacosmos and Vifor. J. P. reports a research grant to institution from Novavax related to this manuscript, and being co-applicant for a Haywood Foundation grant and for a National Institute for Health and Care Research (NIHR)/Clinical Research Network (CRN) COVID Innovation and Insight grant. P. A. S. reports a research grant to institution from Novavax related to this manuscript, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer and AstraZeneca; support for attending meetings and/or travel from Bayer; and participation on a DSMB or advisory board for Bayer. E. C. T. reports a research grant to institution from Novavax related to this manuscript, research grants to institution from Valneva, COV-BOOST, Medical Research Council (MRC), Wellcome, and Public Health Scotland; payment to author for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Wellcome Connecting Science—Sanger Institute; support for attending meetings and/or travel, paid to author, from Wellcome Connecting Science—Sanger Institute, University of Oxford, University of Cambridge, and University of Manchester; and unpaid leadership or fiduciary roles with the Scottish Committee for Pandemic Preparedness, UK Health Security Agency (HSA) technical groups, and the Scottish Genomics Oversight Group. J. T. reports Quin Technologies consulting fees; participation as chair of the Data Monitoring and Ethics Committee (DMEC) for the NIFTY Trial, an NIHR-funded trial; and a role as clinical advisor to Parathyroid UK, a patient support charity. S. I., C. J., H. N., D. B., A. Hi., R. S., I. M., A. M., R. C., D. N. B., D. S., E. P. G., J. B., R. L. S., A. He., C. M., C. P., and F. B. report a research grant to institution from Novavax related to this manuscript. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)