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A T cell-targeted multi-antigen vaccine generates robust cellular and humoral immunity against SARS-CoV-2 infection
oleh: Stephen Boulton, Joanna Poutou, Rida Gill, Nouf Alluqmani, Xiaohong He, Ragunath Singaravelu, Mathieu J.F. Crupi, Julia Petryk, Bradley Austin, Leonard Angka, Zaid Taha, Iris Teo, Siddarth Singh, Rameen Jamil, Ricardo Marius, Nikolas Martin, Taylor Jamieson, Taha Azad, Jean-Simon Diallo, Carolina S. Ilkow, John C. Bell
Format: | Article |
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Diterbitkan: | Elsevier 2023-12-01 |
Deskripsi
SARS-CoV-2, the etiological agent behind the coronavirus disease 2019 (COVID-19) pandemic, has continued to mutate and create new variants with increased resistance against the WHO-approved spike-based vaccines. With a significant portion of the worldwide population still unvaccinated and with waning immunity against newly emerging variants, there is a pressing need to develop novel vaccines that provide broader and longer-lasting protection. To generate broader protective immunity against COVID-19, we developed our second-generation vaccinia virus-based COVID-19 vaccine, TOH-VAC-2, encoded with modified versions of the spike (S) and nucleocapsid (N) proteins as well as a unique poly-epitope antigen that contains immunodominant T cell epitopes from seven different SARS-CoV-2 proteins. We show that the poly-epitope antigen restimulates T cells from the PBMCs of individuals formerly infected with SARS-CoV-2. In mice, TOH-VAC-2 vaccination produces high titers of S- and N-specific antibodies and generates robust T cell immunity against S, N, and poly-epitope antigens. The immunity generated from TOH-VAC-2 is also capable of protecting mice from heterologous challenge with recombinant VSV viruses that express the same SARS-CoV-2 antigens. Altogether, these findings demonstrate the effectiveness of our versatile vaccine platform as an alternative or complementary approach to current vaccines.