Journal article

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

Hareth A Al-Wassiti, Stewart A Fabb, Samantha L Grimley, Ruby Kochappan, Joan K Ho, Chinn Yi Wong, Chee Wah Tan, Thomas J Payne, Asuka Takanashi, Chee Leng Lee, Rekha Shandre Mugan, Horatio Sicilia, Serena LY Teo, Julie McAuley, Paula Ellenberg, James P Cooney, Kathryn C Davidson, Richard Bowen, Marc Pellegrini, Steven Rockman Show all

Molecular Therapy: Methods & Clinical Development | Elsevier | Published : 2024

Abstract

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole-spike vaccines, sVNT studies suggested that BA.1 and BA.5 RBD-TM vaccines had the potential to overco..

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