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Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV\u2010D in rhesus macaques against SARS\u2010CoV\u20102 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1\u2009mg dose by NIS), II (2\u2009mg dose by NIS), III (1\u2009mg dose by NFIS), IV (2\u2009mg dose by NFIS) and V (phosphate\u2010buffer saline [PBS]). The macaques were immunized with the vaccine candidates\/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS\u2010CoV\u20102 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Among\u00a0all the five groups, 2\u2009mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post\u2010SARS\u2010CoV\u20102 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2\u2009mg ZyCoV\u2010D vaccine candidate.<\/jats:p>","DOI":"10.1002\/jmv.28484","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T11:35:26Z","timestamp":1673350526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Needle\u2010free injection system delivery of ZyCoV\u2010D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS\u2010CoV\u20102"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-7166","authenticated-orcid":false,"given":"Pragya D.","family":"Yadav","sequence":"first","affiliation":[{"name":"Indian Council of Medical Research\u2010National Institute of Virology Pune Maharashtra 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