mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting DOI Creative Commons
Hareth Al-Wassiti, Stewart A. Fabb, Samantha L. Grimley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 4, 2023

Abstract To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion variant RBD, transmembrane (TM) and cytoplasmic tail (CT) fragments SARS-CoV-2 spike protein. In naive mice, RBD-TM against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity range RBDs. setting heterologous boost, background exposure to whole sVNT studies suggested that were able overcome detrimental effects immune imprinting. BA.5 booster serum antibodies with 12 22-fold higher RBD than their equivalent variants. Boosting provided good protection more recent variants including XBB XBB.1.5. Each is 28% length its equivalent. This advantage will enable tetravalent be developed at well-tolerated doses formulated mRNA. One Sentence Summary RBDs mutants are effective can imprinting in mice

Language: Английский

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting DOI Creative Commons
Hareth Al-Wassiti, Stewart A. Fabb, Samantha L. Grimley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 4, 2023

Abstract To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion variant RBD, transmembrane (TM) and cytoplasmic tail (CT) fragments SARS-CoV-2 spike protein. In naive mice, RBD-TM against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity range RBDs. setting heterologous boost, background exposure to whole sVNT studies suggested that were able overcome detrimental effects immune imprinting. BA.5 booster serum antibodies with 12 22-fold higher RBD than their equivalent variants. Boosting provided good protection more recent variants including XBB XBB.1.5. Each is 28% length its equivalent. This advantage will enable tetravalent be developed at well-tolerated doses formulated mRNA. One Sentence Summary RBDs mutants are effective can imprinting in mice

Language: Английский

Citations

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