| Autor: |
Abt, Evan R., Lam, Alex K., Miyako Noguchi, Rashid, Khalid, McLaughlin, Jami, Pu-Lin Teng, Tran, Wendy, Donghui Cheng, Nesterenko, Pavlo A., Zhiyuan Mao, Creech, Amanda L., Sojo, Giselle Burton, Jeyachandran, Arjit Vijey, Tam, Ying K., Henley, Jill E., Comai, Lucio, Pardi, Norbert, Arumugaswami, Vaithilingaraja, Witte, Owen N., Radu, Caius G. |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 12/3/2024, Vol. 121 Issue 49, p1-12, 17p |
| Abstrakt: |
Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T cell responses as well as protection against lethal SARS-CoV-2 challenge in human ACE2 transgenic mice. In HLA-A2.1 transgenic mice, the RdRp vaccine elicits CD8+ T cell responses against HLA-A* 02:01-restricted epitopes recognized by human donor T cells. These results highlight RdRp as a candidate antigen for COVID-19 vaccines. The findings also offer insights into crafting effective multivalent mRNA vaccines to broaden CD8+ T cell responses against SARS-CoV-2 and potentially other viruses with pandemic potential. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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