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

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

Déclaration de conflit d'intérêts

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.