SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern
Open Access
- 24 May 2023
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 14, 1195299
- https://doi.org/10.3389/fimmu.2023.1195299
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Here we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in SARS-CoV-2 variants challenge. Results showed RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice. Taken together, our data suggest RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.This publication has 71 references indexed in Scilit:
- Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virusHuman Vaccines & Immunotherapeutics, 2016
- Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large AnimalsMolecular Therapy, 2015
- Pathophysiology of T follicular helper cells in humans and miceNature Immunology, 2015
- Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus InfectionJournal of Virology, 2014
- Understanding the T cell immune response in SARS coronavirus infectionEmerging Microbes & Infections, 2012
- CD4+T Cells: Differentiation and FunctionsJournal of Immunology Research, 2012
- A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon ChallengeJournal of Virology, 2011
- Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNANucleic Acids Research, 2011
- Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoVThe Journal of Immunology, 2008
- Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cellsBlood, 2006