{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:22:04Z","timestamp":1789046524364,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["MP120810"],"award-info":[{"award-number":["MP120810"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech\/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world\u2019s population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.<\/jats:p>","DOI":"10.3390\/vaccines9030214","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:33:57Z","timestamp":1614803637000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6961","authenticated-orcid":false,"given":"Ahmed","family":"Kandeil","sequence":"first","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-5714","authenticated-orcid":false,"given":"Ahmed","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-2104","authenticated-orcid":false,"given":"Rehab R.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-2240","authenticated-orcid":false,"given":"Rabeh","family":"El-Shesheny","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"El Taweel","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mokhtar R.","family":"Gomaa","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-9398","authenticated-orcid":false,"given":"Mahmoud","family":"Shehata","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-6251","authenticated-orcid":false,"given":"Marawan A.","family":"Elbaset","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed E.","family":"Kayed","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara H.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2159-2511","authenticated-orcid":false,"given":"Yassmin","family":"Moatasim","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia","family":"Kutkat","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha N.","family":"Yassen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa E.","family":"Shabana","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"GabAllah","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina Nabil","family":"Kamel","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura M.","family":"Abo Shama","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Sayes","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira N.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Chemical Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa S.","family":"Elalfy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassim MSA","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa N.","family":"Abd El-Fattah","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Chemical Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem Mohamed","family":"El Hariri","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Abdel Kader","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Chemical Pathology, Medical Division, National Research Centre, Cairo, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Azmy","sequence":"additional","affiliation":[{"name":"Reproductive Health Department, Medical Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazi","family":"Kayali","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA"},{"name":"Human Link, Dubai, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Center of Scientific Excellence for Influenza Virus, Environmental Research Division, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","unstructured":"ICTV (2019, January 01). Virus Taxonomy. Available online: http:\/\/ictvonline.org\/virusTaxonomy.asp:."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.abc1932","article-title":"Development of an inactivated vaccine candidate for SARS-CoV-2","volume":"369","author":"Gao","year":"2020","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/s41591-020-1070-6","article-title":"Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters","volume":"26","author":"Tostanoski","year":"2020","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.cell.2020.06.008","article-title":"Development of an inactivated vaccine candidate, bbibp-corv, with potent protection against sars-cov-2","volume":"182","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"596851","DOI":"10.3389\/fmicb.2020.596851","article-title":"Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibodies in Egyptian Convalescent Plasma Donors","volume":"11","author":"Gomaa","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_6","first-page":"481","article-title":"Comparison of ketamine-xylazine and ketamine-dexmedetomidine anesthesia and intraperitoneal tolerance in rats","volume":"52","author":"Wellington","year":"2013","journal-title":"J. Am. Assoc. Lab. Anim. Sci. JAALAS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jmv.10475","article-title":"Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract","volume":"71","author":"Kajon","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.immuni.2020.03.007","article-title":"SARS-CoV-2 Vaccines: Status Report","volume":"52","author":"Amanat","year":"2020","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/14760584.2017.1357471","article-title":"Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases","volume":"16","author":"Barrett","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.3201\/eid2606.200516","article-title":"Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States","volume":"26","author":"Harcourt","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1089\/vim.2010.0028","article-title":"Immunogenicity and protective efficacy in mice and hamsters of a beta-propiolactone inactivated whole virus SARS-CoV vaccine","volume":"23","author":"Roberts","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chowdhury, P., Topno, R., Khan, S.A., and Mahanta, J. (2015). Comparison of beta-Propiolactone and Formalin Inactivation on Antigenicity and Immune Response of West Nile Virus. Adv. Virol., 2015.","DOI":"10.1155\/2015\/616898"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1086\/422454","article-title":"Fever after immunization: Current concepts and improved future scientific understanding","volume":"39","author":"Kohl","year":"2004","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1016\/j.vaccine.2016.08.051","article-title":"An inflammatory response is essential for the development of adaptive immunity-immunogenicity and immunotoxicity","volume":"34","author":"Nakayama","year":"2016","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1586\/14760584.4.3.419","article-title":"Fever following immunization","volume":"4","author":"Tapiainen","year":"2005","journal-title":"Expert Rev. Vaccines"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41541-019-0132-6","article-title":"The how\u2019s and what\u2019s of vaccine reactogenicity","volume":"4","author":"Herve","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1055\/s-0037-1615898","article-title":"D-dimer testing in the diagnosis of acute venous thromboembolism","volume":"82","author":"Lee","year":"1999","journal-title":"Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1015-9584(09)60277-3","article-title":"Diagnostic value of blood D-dimer level in acute mesenteric ischaemia in the rat: An experimental study","volume":"28","author":"Kulacoglu","year":"2005","journal-title":"Asian J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kulkarni, O.P., Lichtnekert, J., Anders, H.J., and Mulay, S.R. (2016). The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is \u201cInflammation\u201d Always Inflammation?. Mediat. Inflamm., 2016.","DOI":"10.1155\/2016\/2856213"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.advms.2019.12.007","article-title":"Elevated levels of d-dimer are associated with inflammation and disease activity rather than risk of venous thromboembolism in patients with granulomatosis with polyangiitis in long term observation","volume":"65","author":"Borowiec","year":"2020","journal-title":"Adv. Med Sciences"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21037\/amj.2017.02.07","article-title":"Correlation of D-dimer level with the inflammatory conditions: A retrospective study","volume":"2","author":"Bao","year":"2017","journal-title":"AME Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1111\/j.1538-7836.2011.04413.x","article-title":"Influenza vaccination and hemostasis: No sustainable procoagulant effects from 2009 H1N1 influenza vaccine in healthy healthcare workers","volume":"9","author":"Smit","year":"2011","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.1038\/s41467-020-20228-7","article-title":"A single dose of recombinant VSV-G-spike vaccine provides protection against SARS-CoV-2 challenge","volume":"11","author":"Tamir","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rosenke, K., Meade-White, K., Letko, M., Clancy, C., Hansen, F., Liu, Y., Okumura, A., Tang-Huau, T.L., Li, R., and Saturday, G. (2020). Defining the Syrian hamster as a highly susceptible preclinical model for SARS-CoV-2 infection. BioRxiv.","DOI":"10.1101\/2020.09.25.314070"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pandey, K., Acharya, A., Mohan, M., Ng, C.L., Reid, S.P., and Byrareddy, S.N. (2020). Animal models for SARS-CoV-2 research: A comprehensive literature review. Transbound Emerg. Dis.","DOI":"10.1111\/tbed.13907"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11259-020-09778-9","article-title":"Infectivity, virulence, pathogenicity, host-pathogen interactions of SARS and SARS-CoV-2 in experimental animals: A systematic review","volume":"44","author":"Sarkar","year":"2020","journal-title":"Vet Res. Commun."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:04Z","timestamp":1760160724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["vaccines9030214"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9030214","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]}}}