Adjuvant-dependent effects on the safety and efficacy of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Autor:	Heise M; University of North Carolina at Chapel Hill., Dillard J; University of North Carolina at Chapel Hill., Taft-Benz S; University of North Carolina., Knight A; Dallas Tissue Research., Anderson E; University of North Carolina at Chapel HIll., Pressey K; University of North Carolina at Chapel Hill., Parotti B; University of North Carolina at Chapel Hill., Martinez S; University of North Carolina at Chapel Hill., Diaz J; University of North Carolina at Chapel Hill., Sarkar S; Southern Research., Madden E; EpiCypher., De la Cruz G; University of North Carolina at Chapel Hill., Adams L; Gryphon Scientific LLC., Dinnon K 3rd; The Rockefeller University., Leist S; University of North Carolina at Chapel Hill., Martinez D; Yale University., Schaefer A; University of North Carolina at Chapel Hill., Powers J; University of North Carolina at Chapel Hill., Yount B; Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill., Castillo I; University of North Carolina at Chapel Hill., Morales N; University of North Carolina at Chapel Hill., Burdick J; University of North Carolina at Chapel Hill., Evangelista MK; University of North Carolina at Chapel Hill., Ralph L; University of North Carolina at Chapel Hill., Pankow N; University of North Carolina at Chapel Hill., Linnertz C; University of North Carolina at Chapel Hill., Lakshmanane P; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC., Montgomery S; University of North Carolina at Chapel Hill., Ferris M; University of North Carolina., Baric R; University of North Carolina at Chapel Hill., Baxter V; Texas Biomedical Research Institute, San Antonio, Texas, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Oct 27. Date of Electronic Publication: 2023 Oct 27.
DOI:	10.21203/rs.3.rs-3401539/v1
Abstrakt:	Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease. Consistent with human results, iCoV2 + Alum protected against homologous challenge. However, challenge with a heterologous SARS-related coronavirus, Rs-SHC014-CoV (SHC014), up to at least 10 months post-vaccination, resulted in VAERD in iCoV2 + Alum-vaccinated animals, characterized by pulmonary eosinophilic infiltrates, enhanced pulmonary pathology, delayed viral clearance, and decreased pulmonary function. In contrast, vaccination with iCoV2 in combination with an alternative adjuvant (RIBI) did not induce VAERD and promoted enhanced SHC014 clearance. Further characterization of iCoV2 + Alum-induced immunity suggested that CD4 + T cells were a major driver of VAERD, and these responses were partially reversed by re-boosting with recombinant Spike protein + RIBI adjuvant. These results highlight potential risks associated with vaccine breakthrough in recipients of Alum-adjuvanted inactivated vaccines and provide important insights into factors affecting both the safety and efficacy of coronavirus vaccines in the face of heterologous virus infections. Competing Interests: Declarations of Interest / Conflicts of Interest RSB has served on the Scientific Advisory Boards for Takeda vaccines, VaxArt and Invivyd Therapeutics, and has collaborations with Gilead, Janssen Pharmaceuticals, Pardas Biosciences, and Chimerix. RSB, KHD III and SRL are listed as inventors on patents pertaining to the mouse-adapted SARS-CoV-2 viruses (MA10 and MA10-B.1.351; Patent number 11,225,508) and the SARS-CoV-2 nanoLuciferase viruses (SARS-CoV-2-nLuc and B.1.351-nLuc; Patent number 11,492,379) used in this study. In accordance with the Nature Portfolio Competing interests policy, this section is also stated at the end of this manuscript.
Databáze:	MEDLINE
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