Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission
Chengjin Ye, Jun‐Gyu Park, Kevin Chiem, Piyush Dravid, Anna Allué‐Guardia, Andreu Garcia‐Vilanova, Paula Pino Tamayo, Vinay Shivanna, Amit Kapoor, Mark R. Walter, James J. Kobie, Richard K. Plemper, Jordi B. Torrelles, Luis Martínez‐Sobrido
Abstract
Live-attenuated vaccines (LAVs) are able to induce robust immune responses, including both humoral and cellular immunity, representing a very promising option to provide broad and long-term immunity. To develop LAVs for SARS-CoV-2, we engineered attenuated recombinant SARS-CoV-2 (rSARS-CoV-2) that simultaneously lacks the viral open reading frame 3a (ORF3a) in combination with either ORF6, ORF7a, or ORF7b (Δ3a/Δ6, Δ3a/Δ7a, and Δ3a/Δ7b, respectively) proteins. Among them, the rSARS-CoV-2 Δ3a/Δ7b was completely attenuated and able to provide 100% protection against an otherwise lethal challenge in K18 hACE2 transgenic mice. Moreover, the rSARS-CoV-2 Δ3a/Δ7b conferred protection against viral transmission between golden Syrian hamsters.