Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters

Abstract

Vaccines have been central in ending the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants increasingly escape first-generation vaccine protection. To fill this gap, live particle-based vaccines mimicking natural infection aim at protecting against a broader spectrum of virus variants. We designed "single-cycle SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess superior immune-modulatory features and provide an excellent safety profile in the Syrian hamster model. Full protection of all intranasally vaccinated animals was achieved against an autologous challenge with SARS-CoV-2 virus using an Envelope-gene-deleted vaccine candidate. By deleting key immune-downregulating genes, sterilizing immunity was achieved with an advanced candidate without virus spread to contact animals. Hence, SCVs have the potential to induce a broad and durable protection against COVID-19 superior to a natural infection.

Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform

“…Further, CLEVER was used for related substantial manipulations, including the complete deletion of the Envelope gene (E) which led to the creation of a single-cycle virus that may serve as a live, replication-incompetent vaccine candidate (Lett et al, 2023).…”