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GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and GEMCOVAC-19 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001), but not in the ChAdOx1 nCoV-19 arm (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio &gt;1 and difference in seroconversion &gt;0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ctri.nic.in\/Clinicaltrials\/pmaindet2.php?EncHid=NjY5MDM=&amp;Enc=&amp;userName=gemcovac\">CTRI\/2022\/10\/046475<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-024-02955-2","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T06:19:29Z","timestamp":1713421169000},"page":"1363-1372","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2\/3 randomized trial"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7952-9212","authenticated-orcid":false,"given":"Amit","family":"Saraf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3495-2563","authenticated-orcid":false,"given":"Rohan","family":"Gurjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarnendu","family":"Kaviraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3509-0398","authenticated-orcid":false,"given":"Aishwarya","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7413-3987","authenticated-orcid":false,"given":"Durgesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruta","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-9626","authenticated-orcid":false,"given":"Rashmi","family":"Virkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashri","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekta","family":"Baranwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9619-2364","authenticated-orcid":false,"given":"Ajay","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Raghuwanshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4551-9118","authenticated-orcid":false,"given":"Praveen","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxman","family":"Savergave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-4606","authenticated-orcid":false,"given":"Sanjay","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the GEMCOVAC-OM Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Pophale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Shende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra Baban","family":"Shinde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Vikhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Karmalkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Deshmukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Bulle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 602, 671\u2013675 (2022).","journal-title":"Nature"},{"key":"2955_CR5","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.vaccine.2024.01.087","volume":"42","author":"R Wadapurkar","year":"2024","unstructured":"Wadapurkar, R., Singh, S. & Singh, A. Leveraging the immunoinformatics approach for designing the SARS-CoV-2 Omicron-specific antigenic cassette of mRNA vaccine. Vaccine 42, 1630\u20131647 (2024).","journal-title":"Vaccine"},{"key":"2955_CR6","doi-asserted-by":"publisher","unstructured":"Comes, J. D. G., Pijlman, G. P. & Hick, T. A. H. Rise of the RNA machines\u2014self-amplification in mRNA vaccine design. 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