{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:12:45Z","timestamp":1776269565406,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PJSC \u201cHuman Stem Cells Institute\u201d"},{"name":"Moscow Seed Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Public health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of \u201cBetuvax-CoV-2\u201d, a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based spherical virus-like nanoparticles as an adjuvant (\u201cBetuspheres\u201d). The study aimed to demonstrate vaccine safety in mice, rats, and Chinchilla rabbits through acute, subchronic, and reproductive toxicity studies. Along with safety, the vaccine demonstrated protective efficacy through SARS-CoV-2-neutralizing antibody production in mice, rats, hamsters, rabbits, and primates (rhesus macaque), and lung damage and infection protection in hamsters and rhesus macaque model. Eventually, \u201cBetuvax-CoV-2\u201d was proved to confer superior efficacy and protection against the SARS-CoV-2 in preclinical studies. Based on the above results, the vaccine was enabled to enter clinical trials that are currently underway.<\/jats:p>","DOI":"10.3390\/vaccines10081290","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T23:05:49Z","timestamp":1660259149000},"page":"1290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["SARS-CoV-2 Subunit Virus-like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-1254","authenticated-orcid":false,"given":"Anna V.","family":"Vakhrusheva","sequence":"first","affiliation":[{"name":"Betuvax LLC, 121096 Moscow, Russia"},{"name":"Department of Bioengineering, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3918-5618","authenticated-orcid":false,"given":"Aleksandr V.","family":"Kudriavtsev","sequence":"additional","affiliation":[{"name":"Betuvax LLC, 121096 Moscow, Russia"},{"name":"Department of Bioengineering, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-776X","authenticated-orcid":false,"given":"Nickolay A.","family":"Kryuchkov","sequence":"additional","affiliation":[{"name":"Clinical Excellence Group LLC, 127051 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-3841","authenticated-orcid":false,"given":"Roman V.","family":"Deev","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, I.I. Mechnikov North-Western State Medical University, 195067 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Frolova","sequence":"additional","affiliation":[{"name":"PJSC Human Stem Cells Institute, 129110 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-0300","authenticated-orcid":false,"given":"Konstantin A.","family":"Blagodatskikh","sequence":"additional","affiliation":[{"name":"Center of Genetics and Reproductive Medicine \u201cGenetico\u201d, 119333 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-3290","authenticated-orcid":false,"given":"Milana","family":"Djonovic","sequence":"additional","affiliation":[{"name":"Betuvax LLC, 121096 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5915-7999","authenticated-orcid":false,"given":"Andrey A.","family":"Nedorubov","sequence":"additional","affiliation":[{"name":"Center for Preclinical Studies, Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-5559","authenticated-orcid":false,"given":"Elena","family":"Odintsova","sequence":"additional","affiliation":[{"name":"Center for Preclinical Studies, Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-1914","authenticated-orcid":false,"given":"Aleksandr V.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Biotechnology Developments LLC, 119285 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-398X","authenticated-orcid":false,"given":"Ekaterina A.","family":"Romanovskaya-Romanko","sequence":"additional","affiliation":[{"name":"Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-3820","authenticated-orcid":false,"given":"Marina A.","family":"Stukova","sequence":"additional","affiliation":[{"name":"Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-5117","authenticated-orcid":false,"given":"Artur A.","family":"Isaev","sequence":"additional","affiliation":[{"name":"PJSC Human Stem Cells Institute, 129110 Moscow, Russia"},{"name":"Center of Genetics and Reproductive Medicine \u201cGenetico\u201d, 119333 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5048-7828","authenticated-orcid":false,"given":"Igor V.","family":"Krasilnikov","sequence":"additional","affiliation":[{"name":"Biotechnology Developments LLC, 119285 Moscow, Russia"},{"name":"Department of Vaccinology, Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Srivastava, N., and Saxena, S.K. 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Infect."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/8\/1290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:56Z","timestamp":1760141216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/8\/1290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["vaccines10081290"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10081290","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,10]]}}}