tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Jun 28;100693.
doi: 10.1016/j.xcrm.2022.100693. Online ahead of print.
Mucosal chemokine adjuvant enhances synDNA vaccine-mediated responses to SARS-CoV-2 and provides heterologous protection in vivo
Ebony N Gary[SUP] 1 [/SUP], Nicholas J Tursi[SUP] 2 [/SUP], Bryce Warner[SUP] 3 [/SUP], Elizabeth M Parzych[SUP] 1 [/SUP], Ali R Ali[SUP] 1 [/SUP], Drew Frase[SUP] 1 [/SUP], Estella Moffat[SUP] 4 [/SUP], Carissa Embury-Hyatt[SUP] 4 [/SUP], Trevor R F Smith[SUP] 5 [/SUP], Kate E Broderick[SUP] 5 [/SUP], Laurent Humeau[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Ami Patel[SUP] 1 [/SUP], Daniel W Kulp[SUP] 1 [/SUP], David B Weiner[SUP] 7 [/SUP]
Affiliations
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic has claimed more than 5 million lives. Emerging variants of concern (VOCs) continually challenge viral control. Directing vaccine-induced humoral and cell-mediated responses to mucosal surfaces may enhance vaccine efficacy. Here we investigate the immunogenicity and protective efficacy of optimized synthetic DNA plasmids encoding wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (pS) co-formulated with the plasmid-encoded mucosal chemokine cutaneous T cell-attracting chemokine (pCTACK; CCL27). pCTACK-co-immunized animals exhibit increased spike-specific antibodies at the mucosal surface and increased frequencies of interferon gamma (IFNγ)[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells in the respiratory mucosa. pCTACK co-immunization confers 100% protection from heterologous Delta VOC challenge. This study shows that mucosal chemokine adjuvants can direct vaccine-induced responses to specific immunological sites and have significant effects on heterologous challenge. Further study of this unique chemokine-adjuvanted vaccine approach in the context of SARS-CoV-2 vaccines is likely important.
Keywords: COVID-19; DNA vaccine; SARS-CoV-2; adjuvant; chemokine; mucosal.
. 2022 Jun 28;100693.
doi: 10.1016/j.xcrm.2022.100693. Online ahead of print.
Mucosal chemokine adjuvant enhances synDNA vaccine-mediated responses to SARS-CoV-2 and provides heterologous protection in vivo
Ebony N Gary[SUP] 1 [/SUP], Nicholas J Tursi[SUP] 2 [/SUP], Bryce Warner[SUP] 3 [/SUP], Elizabeth M Parzych[SUP] 1 [/SUP], Ali R Ali[SUP] 1 [/SUP], Drew Frase[SUP] 1 [/SUP], Estella Moffat[SUP] 4 [/SUP], Carissa Embury-Hyatt[SUP] 4 [/SUP], Trevor R F Smith[SUP] 5 [/SUP], Kate E Broderick[SUP] 5 [/SUP], Laurent Humeau[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Ami Patel[SUP] 1 [/SUP], Daniel W Kulp[SUP] 1 [/SUP], David B Weiner[SUP] 7 [/SUP]
Affiliations
- PMID: 35839767
- PMCID: PMC9237025
- DOI: 10.1016/j.xcrm.2022.100693
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic has claimed more than 5 million lives. Emerging variants of concern (VOCs) continually challenge viral control. Directing vaccine-induced humoral and cell-mediated responses to mucosal surfaces may enhance vaccine efficacy. Here we investigate the immunogenicity and protective efficacy of optimized synthetic DNA plasmids encoding wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (pS) co-formulated with the plasmid-encoded mucosal chemokine cutaneous T cell-attracting chemokine (pCTACK; CCL27). pCTACK-co-immunized animals exhibit increased spike-specific antibodies at the mucosal surface and increased frequencies of interferon gamma (IFNγ)[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells in the respiratory mucosa. pCTACK co-immunization confers 100% protection from heterologous Delta VOC challenge. This study shows that mucosal chemokine adjuvants can direct vaccine-induced responses to specific immunological sites and have significant effects on heterologous challenge. Further study of this unique chemokine-adjuvanted vaccine approach in the context of SARS-CoV-2 vaccines is likely important.
Keywords: COVID-19; DNA vaccine; SARS-CoV-2; adjuvant; chemokine; mucosal.