{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:38:11Z","timestamp":1774262291893,"version":"3.50.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016302","name":"Coalition for Epidemic Preparedness Innovations","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016302","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"\n Background<\/jats:title>\n NVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.<\/jats:p>\n <\/jats:sec>\n \n Methods and findings<\/jats:title>\n \n The phase 2 component of our randomized, placebo-controlled, phase 1 to 2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late-phase studies and was based on immunogenicity and safety data through Day 35 (14 days after the second dose). The trial was conducted at 9 sites in Australia and 8 sites in the United States. Participants in 2 age groups (aged 18 to 59 and 60 to 84 years) were randomly assigned to receive either 1 or 2 intramuscular doses of 5-\u03bcg or 25-\u03bcg NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response. After enrollment, 1,288 participants were randomly assigned to 1 of 4 vaccine groups or placebo, with 1,283 participants administered at least 1 study treatment. Of these, 45% were older participants 60 to 84 years. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose. Reactogenicity occurred less frequently and was of lower intensity in older participants. Both 2-dose regimens of 5-\u03bcg and 25-\u03bcg NVX-CoV2373 induced robust immune responses in younger and older participants. For the 2-dose regimen of 5 \u03bcg, geometric mean titers (GMTs) for IgG anti-spike protein were 65,019 (95% confidence interval (CI) 55,485 to 76,192) and 28,137 (95% CI 21,617 to 36,623) EU\/mL and for wild-type virus neutralizing antibody (with an inhibitory concentration of 50%\u2014MN\n 50%<\/jats:sub>\n ) were 2,201 (95% CI 1,343 to 3,608) and 981 (95% CI 560 to 1,717) titers for younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in a panel of convalescent sera for both age groups. Study limitations include the relatively short duration of safety follow-up to date and current lack of immune persistence data beyond the primary vaccination regimen time point assessments, but these data will accumulate over time.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The study confirmed the phase 1 findings that the 2-dose regimen of 5-\u03bcg NVX-CoV2373 is highly immunogenic and well tolerated in younger adults. In addition, in older adults, the 2-dose regimen of 5 \u03bcg was also well tolerated and showed sufficient immunogenicity to support its use in late-phase efficacy studies.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n NCT04368988<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pmed.1003769","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T13:26:37Z","timestamp":1633094797000},"page":"e1003769","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":91,"title":["Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6696-3975","authenticated-orcid":true,"given":"Neil","family":"Formica","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2563-9981","authenticated-orcid":true,"given":"Raburn","family":"Mallory","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-586X","authenticated-orcid":true,"given":"Gary","family":"Albert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-8919","authenticated-orcid":true,"given":"Michelle","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce S.","family":"Plested","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iksung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5125-9296","authenticated-orcid":true,"given":"Andreana","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Dubovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory M.","family":"Glenn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the 2019nCoV-101 Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"pmed.1003769.ref001","volume-title":"Coronavirus disease (COVID-19) dashboard","author":"World Health Organization","year":"2021"},{"issue":"16","key":"pmed.1003769.ref002","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.vaccine.2016.02.033","article-title":"Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola\/Makona virus glycoprotein (GP) nanoparticle vaccine in mice","volume":"34","author":"KL Bengtsson","year":"2016","journal-title":"Vaccine"},{"issue":"24","key":"pmed.1003769.ref003","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1056\/NEJMoa2026920","article-title":"Phase 1\u20132 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine","volume":"383","author":"C Keech","year":"2020","journal-title":"N Engl J Med"},{"issue":"3","key":"pmed.1003769.ref004","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro2090","article-title":"The spike protein of SARS-CoV\u2013a target for vaccine and therapeutic development","volume":"7","author":"L Du","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"6","key":"pmed.1003769.ref005","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"W Tai","year":"2020","journal-title":"Cell Mol Immunol"},{"issue":"5","key":"pmed.1003769.ref006","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"LR Baden","year":"2021","journal-title":"N Engl J Med"},{"issue":"27","key":"pmed.1003769.ref007","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"C4591001 Clinical Trial Group. 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