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Nat Commun . A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Aug 26;15(1):7225.
doi: 10.1038/s41467-024-51535-y. A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants

Xiang Liu[SUP] 1 2 3 [/SUP], Wern Hann Ng[SUP] 1 2 3 [/SUP], Eva Zusinaite[SUP] 4 [/SUP], Joseph Freitas[SUP] 1 2 3 [/SUP], Adam Taylor[SUP] 1 2 3 [/SUP], Venugopal Yerragunta[SUP] 5 [/SUP], Shukra Madhaha Aavula[SUP] 5 [/SUP], Sambaiah Gorriparthi[SUP] 5 [/SUP], Santhakumar Ponsekaran[SUP] 5 [/SUP], Rama Lakshmi Bonda[SUP] 5 [/SUP], Priyanka Mani[SUP] 5 [/SUP], Sridevi V Nimmagadda[SUP] 5 [/SUP], Sainan Wang[SUP] 4 [/SUP], Laura Sandra Lello[SUP] 4 [/SUP], Ali Zaid[SUP] 1 2 3 [/SUP], Ujjwal Dua[SUP] 1 6 [/SUP], Sharon A Taft-Benz[SUP] 7 [/SUP], Elizabeth Anderson[SUP] 7 [/SUP], Victoria K Baxter[SUP] 7 [/SUP], Sanjay Sarkar[SUP] 7 [/SUP], Zheng L Ling[SUP] 8 [/SUP], Thomas M Ashhurst[SUP] 8 9 [/SUP], Samuel M S Cheng[SUP] 10 [/SUP], Priyabrata Pattnaik[SUP] 5 [/SUP], Anand Kumar Kanakasapapathy[SUP] 5 [/SUP], Ralph S Baric[SUP] 7 [/SUP], Felicity J Burt[SUP] 11 [/SUP], Malik Peiris[SUP] 10 12 [/SUP], Mark T Heise[SUP] 7 [/SUP], Nicholas J C King[SUP] 1 8 13 14 15 [/SUP], Andres Merits[SUP] 4 [/SUP], Rajendra Lingala[SUP] 5 [/SUP], Suresh Mahalingam[SUP] 16 17 18 [/SUP]



Affiliations
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.


 
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