BibTex format
@article{De:2026:10.1016/j.omtn.2026.102918,
author = {De, Chiara A and Giachino, C and Pirillo, MF and Campanile, A and Pellino, E and Gallinaro, A and Froechlich, G and Falce, C and Scognamiglio, A and Totaro, S and Liguori, MV and Peltrini, R and De, Simone A and Capone, S and Pietro, Z and Negri, D and Cara, A and Nicosia, A and Sasso, E},
doi = {10.1016/j.omtn.2026.102918},
journal = {Mol Ther Nucleic Acids},
title = {Broadly cross-reactive mRNA COVID-19 vaccine encoding trimeric RBDs and NSP12 mitigates immune imprinting.},
url = {http://dx.doi.org/10.1016/j.omtn.2026.102918},
volume = {37},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The continuous evolution of SARS-CoV-2 variants, driven by mutations in the spike protein undermines viral recognition by antibodies elicited through prior infection or vaccination with the ancestral Wuhan strain. Original antigenic sin of SARS-CoV-2 ancestral virus or vaccine led to a weakened neutralizing antibody response against successive variants upon administration of an updated vaccine. On the contrary, T cells retain cross-reactivity thanks to the high density of conserved epitopes. We designed mRNA vaccines encoding single-chain heterotrimers of the receptor-binding domain (RBD) natural variants of interest (VOI), (RBD-VOI) and of phylogenetically informed consensus representing the major variant lineages RBD-consensus (RBD-Cons). We demonstrate a broad neutralizing activity against omicron subvariants and mitigated immune imprinting when RBD-Cons was used as a booster after conventional Wuhan spike priming. To enhance cellular immunity, we designed a second mRNA vaccine component encoding the viral polymerase NSP12 able to induce a cross-reactive T cell response to be combined with the heterotrimeric RBD vaccine. Our results offer a rational strategy for next-generation, imprinting-resistant vaccines.
AU - De,Chiara A
AU - Giachino,C
AU - Pirillo,MF
AU - Campanile,A
AU - Pellino,E
AU - Gallinaro,A
AU - Froechlich,G
AU - Falce,C
AU - Scognamiglio,A
AU - Totaro,S
AU - Liguori,MV
AU - Peltrini,R
AU - De,Simone A
AU - Capone,S
AU - Pietro,Z
AU - Negri,D
AU - Cara,A
AU - Nicosia,A
AU - Sasso,E
DO - 10.1016/j.omtn.2026.102918
PY - 2026///
SN - 2162-2531
TI - Broadly cross-reactive mRNA COVID-19 vaccine encoding trimeric RBDs and NSP12 mitigates immune imprinting.
T2 - Mol Ther Nucleic Acids
UR - http://dx.doi.org/10.1016/j.omtn.2026.102918
UR - https://www.ncbi.nlm.nih.gov/pubmed/42023032
VL - 37
ER -