TY - JOUR T1 - A bacteriophage-based, highly efficacious, needle and adjuvant-free, mucosal COVID-19 vaccine JF - bioRxiv DO - 10.1101/2022.04.28.489809 SP - 2022.04.28.489809 AU - Jingen Zhu AU - Swati Jain AU - Jian Sha AU - Himanshu Batra AU - Neeti Ananthaswamy AU - Paul B. Kilgore AU - Emily K. Hendrix AU - Yashoda M. Hosakote AU - Xiaorong Wu AU - Juan P. Olano AU - Adeyemi Kayode AU - Cristi L. Galindo AU - Simran Banga AU - Aleksandra Drelich AU - Vivian Tat AU - Chien-Te K. Tseng AU - Ashok K. Chopra AU - Venigalla B. Rao Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/04/29/2022.04.28.489809.abstract N2 - The authorized mRNA- and adenovirus-based SARS-CoV-2 vaccines are intramuscularly injected and effective in preventing COVID-19, but do not induce efficient mucosal immunity, or prevent viral transmission. We developed a bacteriophage T4-based, multicomponent, needle and adjuvant-free, mucosal vaccine by engineering spike trimers on capsid exterior and nucleocapsid protein in the interior. Intranasal administration of T4-COVID vaccine induced higher virus neutralization antibody titers against multiple variants, balanced Th1/Th2 antibody and cytokine responses, stronger CD4+ and CD8+ T cell immunity, and higher secretory IgA titers in sera and bronchoalveolar lavage with no effect on the gut microbiota, compared to vaccination of mice intramuscularly. The vaccine is stable at ambient temperature, induces apparent sterilizing immunity, and provides complete protection against original SARS-CoV-2 strain and its Delta variant with minimal lung histopathology. This mucosal vaccine is an excellent candidate for boosting immunity of immunized and/or as a second-generation vaccine for the unimmunized population.Competing Interest StatementThe authors have declared no competing interest. ER -