A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters

Phanramphoei Namprachan Frantz ,David Hardy,Hervé Bourhy,Claude Ruffié,Frédéric Tangy,Valérie Najburg,Guilherme Dias De Melo,Aleksandr Barinov,Xavier Montagutelli,Jean-Nicolas Tournier,Anan Jongkaewwattana,Laurine Conquet,Chantal Combredet,Hélène Strick‐Marchand ,James P Di Santo ,Emmanuelle Billon-Denis,Lauriane Kergoat,Samaporn Teeravechyan,Etienne Simon‐Lorière ,Magali Tichit,Priyanka Fernandes,Laurine Levillayer,Florence Larrous,Matthieu Prot

doi:10.1038/s41467-021-26506-2

Abstract

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.

Highlights

Several COVID-19 vaccines have been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants
Based on our previous work with measles vaccine (MV) expressing SARS-CoV-1 S, in which the surfaceexpressed full-length antigen showed higher immunogenicity[12] and since SARS-CoV and SARS-CoV-2 S proteins share a high degree of similarity[24], the full-length S protein of SARS-CoV-2 with transmembrane domain was chosen as the main antigen to be expressed by the MV vector
We introduced a number of modifications in the native S sequence (Fig. 1), including human codon-optimization and mutation of two prolines, K986P and V987P, in the S2 region, following a proven strategy to stabilize the S protein in its prefusion conformation, increasing its expression and immunogenicity[25,26,27]

Summary

Introduction

Several COVID-19 vaccines have been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1dominant T-cell responses and high neutralizing antibody titers. After exceptional commitment from the scientific and industrial communities over the past year, several vaccines have been successfully developed in an amazingly accelerated time frame, approved by health authorities, and effectively deployed in many countries These vaccines based on messenger RNA (mRNA) and adenovirus vectors have demonstrated high levels of protection from COVID-191–3. The live attenuated measles vaccine (MV) is one of the safest and most efficacious human preventive medicines It elicits neutralizing antibodies and robust, long-lasting Th1 cellular responses, making it an attractive candidate for SARS-CoV-2 vaccination with minimal risk of vaccine-associated enhanced respiratory disease (VAERD)[6]. A number of recombinant MV (rMV)-based vaccines against viral pathogens are currently in preclinical and clinical trials[17]

Methods

Results

Conclusion