A Self-Amplifying RNA Vaccine Protects Against SARS-CoV-2 (D614G) and Alpha Variant of Concern (B.1.1.7) in a Transmission-Challenge Hamster Model

Abstract

Vaccines for SARS-CoV-2 have been hugely successful in alleviating hospitalization and deaths caused by the newly emerged coronavirus that is the cause of COVID. However, although the parentally administered vaccines are very effective at reducing severe disease, they do not induce sterilizing immunity. As the virus continues to circulate around the globe, it is still not clear how long protection will last, nor whether variants will emerge that escape vaccine immunity. Animal models can be useful to complement studies of antigenicity of novel variants and inform decision making about the need for vaccine updates. The Syrian golden hamster is the preferred small animal model for SARS-CoV-2 infection. Since virus is efficiently transmitted between hamsters, we developed a transmission challenge model that presents a more natural dose and route of infection than the intranasal challenge usually employed. Our studies demonstrate that an saRNA vaccine based on the earliest Wuhan-like virus spike sequence induced neutralizing antibodies in sera of immunized hamsters at similar titres to those in human convalescent sera or vaccine recipients. The saRNA vaccine was equally effective at abrogating clinical signs in animals who acquired through exposure to cagemates infected either with a virus isolated in summer 2020 or with a representative Alpha (B.1.1.7) variant isolated in December 2020. The vaccine also reduced shedding of infectious virus from the nose, further reinforcing its likely effectiveness at reducing onwards transmission. This model can be extended to test the effectiveness of vaccination in blocking infections with and transmission of novel variants as they emerge.

Note:
Funding Information: This study was supported by The Bill and Melinda Gates Foundation [INV-016635]. We acknowledge the G2P-UK National Virology consortium funded by MRC/UKRI (grant ref: MR/W005611/1) for contributing funding for this work. RK was supported by Wellcome fellowship no. 216353/Z/19/Z.

Declaration of Interests: Robin Shattock and Paul McKay RJS and PFM are co-inventors on a patent application covering this SARS-CoV-2 saRNA vaccine. All other authors have nothing to declare.

Ethics Approval Statement: All work performed was approved by the local genetic manipulation (GM) safety committee of 217 Imperial College London, St. Mary’s Campus (centre number GM77), and the Health and Safety 218 Executive of the United Kingdom, under reference CBA1.77.20.1. Animal research was carried out 219 under a United Kingdom Home Office License, P48DAD9B4.

Keywords: SARS-CoV-2, variant, saRNA, hamster, Transmission