Mucosal chemokine adjuvant enhances synDNA vaccine-mediated responses to SARS-CoV-2 and provides heterologous protection in vivo.

Autor:	Gary EN; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Tursi NJ; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Warner B; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada., Parzych EM; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Ali AR; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Frase D; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Moffat E; National Center for Foreign Animal Disease (NCFAD), Canadian Food Inspection Agency, Winnipeg, MB, Canada., Embury-Hyatt C; National Center for Foreign Animal Disease (NCFAD), Canadian Food Inspection Agency, Winnipeg, MB, Canada., Smith TRF; Inovio Pharmaceuticals, Bluebell, PA, USA., Broderick KE; Inovio Pharmaceuticals, Bluebell, PA, USA., Humeau L; Inovio Pharmaceuticals, Bluebell, PA, USA., Kobasa D; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada., Patel A; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Kulp DW; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA., Weiner DB; The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA. Electronic address: dweiner@wistar.org.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2022 Jul 19; Vol. 3 (7), pp. 100693. Date of Electronic Publication: 2022 Jun 28.
DOI:	10.1016/j.xcrm.2022.100693
Abstrakt:	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) + CD8 + 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. Competing Interests: Declarations of interests D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. Remuneration received by D.B.W. includes direct payments and stock or stock options. D.B.W. discloses the following paid associations with commercial partners: GeneOne (consultant), Geneos (advisory board), AstraZeneca (advisory board, speaker), Inovio (BOD, SRA, stock), Sanofi (advisory board), and BBI (advisory board). (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu