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

Martin Joseph Lett; Fabian Otte; David Hauser; Jacob Schön; Enja Tatjana Kipfer; Donata Hoffmann; Nico Joël Halwe; Lorenz Ulrich; Yuepeng Zhang; Vladimir Cmiljanović; Claudia Wylezich; Lorena Urda; Christopher M. R. Lang; Martin Beer; Christian Mittelholzer; Thomas Klimkait

doi:10.1101/2023.05.17.541127

Molecular BiologybioRxivMay 17, 2023

Preprint

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

Martin Joseph Lett iD, Fabian Otte iD, David Hauser iD, Jacob Schön iD, Enja Tatjana Kipfer iD, Donata Hoffmann iD, Nico Joël Halwe iD, Lorenz Ulrich iD, Yuepeng Zhang iD, Vladimir Cmiljanović, Claudia Wylezich iD, Lorena Urda iD, Christopher M. R. Lang iD, Martin Beer iD, Christian Mittelholzer iD, Thomas Klimkait iD

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.

PDF DOI