| Autor: |
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 L.Y. Teo, Julie McAuley, Paula Ellenberg, James P. Cooney, Kathryn C. Davidson, Richard Bowen, Marc Pellegrini, Steven Rockman, Dale I. Godfrey, Terry M. Nolan, Lin-fa Wang, Georgia Deliyannis, Damian F.J. Purcell, Colin W. Pouton |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 32, Iss 4, Pp 101380- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2024.101380 |
| Popis: |
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 overcome the detrimental effects of immune imprinting. A subsequent heterologous boost study using XBB.1.5 booster vaccines was evaluated using both sVNT and authentic virus neutralization. Geometric mean XBB.1.5 neutralization values after third-dose RBD-TM or whole-spike XBB.1.5 booster vaccines were compared with those after a third dose of ancestral spike booster vaccine. Fold-improvement over ancestral vaccine was just 1.3 for the whole-spike XBB.1.5 vaccine, similar to data published using human serum samples. In contrast, the fold-improvement achieved by the RBD-TM XBB.1.5 vaccine was 16.3, indicating that the RBD-TM vaccine induced the production of antibodies that neutralize the XBB.1.5 variant despite previous exposure to ancestral spike protein. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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