tetano
Editor, Senior Moderator
Mol Ther Methods Clin Dev
. 2023 Sep 16:31:101110.
doi: 10.1016/j.omtm.2023.101110. eCollection 2023 Dec 14. A T cell-targeted multi-antigen vaccine generates robust cellular and humoral immunity against SARS-CoV-2 infection
Stephen Boulton[SUP] 1 2 [/SUP], Joanna Poutou[SUP] 1 2 [/SUP], Rida Gill[SUP] 1 [/SUP], Nouf Alluqmani[SUP] 1 2 [/SUP], Xiaohong He[SUP] 1 [/SUP], Ragunath Singaravelu[SUP] 1 2 [/SUP], Mathieu J F Crupi[SUP] 1 2 [/SUP], Julia Petryk[SUP] 1 [/SUP], Bradley Austin[SUP] 1 [/SUP], Leonard Angka[SUP] 1 [/SUP], Zaid Taha[SUP] 1 2 [/SUP], Iris Teo[SUP] 1 3 [/SUP], Siddarth Singh[SUP] 1 [/SUP], Rameen Jamil[SUP] 1 [/SUP], Ricardo Marius[SUP] 1 2 [/SUP], Nikolas Martin[SUP] 1 [/SUP], Taylor Jamieson[SUP] 1 2 [/SUP], Taha Azad[SUP] 1 2 4 5 [/SUP], Jean-Simon Diallo[SUP] 1 2 [/SUP], Carolina S Ilkow[SUP] 1 2 [/SUP], John C Bell[SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; nucleocapsid; poly-epitope; spike; t cell; vaccine; vaccinia virus.
. 2023 Sep 16:31:101110.
doi: 10.1016/j.omtm.2023.101110. eCollection 2023 Dec 14. A T cell-targeted multi-antigen vaccine generates robust cellular and humoral immunity against SARS-CoV-2 infection
Stephen Boulton[SUP] 1 2 [/SUP], Joanna Poutou[SUP] 1 2 [/SUP], Rida Gill[SUP] 1 [/SUP], Nouf Alluqmani[SUP] 1 2 [/SUP], Xiaohong He[SUP] 1 [/SUP], Ragunath Singaravelu[SUP] 1 2 [/SUP], Mathieu J F Crupi[SUP] 1 2 [/SUP], Julia Petryk[SUP] 1 [/SUP], Bradley Austin[SUP] 1 [/SUP], Leonard Angka[SUP] 1 [/SUP], Zaid Taha[SUP] 1 2 [/SUP], Iris Teo[SUP] 1 3 [/SUP], Siddarth Singh[SUP] 1 [/SUP], Rameen Jamil[SUP] 1 [/SUP], Ricardo Marius[SUP] 1 2 [/SUP], Nikolas Martin[SUP] 1 [/SUP], Taylor Jamieson[SUP] 1 2 [/SUP], Taha Azad[SUP] 1 2 4 5 [/SUP], Jean-Simon Diallo[SUP] 1 2 [/SUP], Carolina S Ilkow[SUP] 1 2 [/SUP], John C Bell[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37822719
- PMCID: PMC10562195
- DOI: 10.1016/j.omtm.2023.101110
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.
Keywords: COVID-19; SARS-CoV-2; nucleocapsid; poly-epitope; spike; t cell; vaccine; vaccinia virus.