tetano
Editor, Senior Moderator
J Med Virol
. 2024 Sep;96(9):e29893.
doi: 10.1002/jmv.29893. Glycan masking of NTD loops with a chimeric RBD of the spike protein as a vaccine design strategy against emerging SARS-CoV-2 Omicron variants
Hao-Chan Hung[SUP] 1 [/SUP], Boon-Fatt Tan[SUP] 2 [/SUP], Wei-Shuo Lin[SUP] 1 [/SUP], Suh-Chin Wu[SUP] 1 3 4 [/SUP]
Affiliations
The N-terminal domain (NTD) of the SARS-CoV-2 S protein comprises five exposed protruding loops. Deletions, insertions, and substitutions within these NTD loops play a significant role in viral evolution and contribute to immune evasion. We reported previously that introducing the glycan masking mutation R158N/Y160T in the NTD loop led to increased titers of neutralizing antibodies against the SARS-CoV-2 Wuhan-Hu-01 strain, as well as the Alpha, Beta, and Delta variants. In this study, we conducted further investigations on 10 additional glycan-masking sites in the NTD loops. Our findings indicate that the introduction of glycan masking mutations, specifically N87/G89T, H146N/N148T, N185/K187T, and V213N/D215T significantly enhanced neutralizing antibody titers against the Delta variant. The combination of dual glycan-masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N results in a shift toward the Omicron BA.1. Furthermore, the introduction of the Omicron receptor binding domain (RBD) alongside these two dual glycan masking mutations of Wuhan-Hu-1 and XBB.1 NTD sequences resulted in a noticeable shift in antigenic distances, aligning with the Omicron BA.4/5, BA.2.75.2, BQ.1.1, and XBB.1 subvariants on the antigenic map. This strategic combination, which involves the dual glycan masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N in the NTD loops, along with the domain swap incorporating the Omicron RBD, emerges as a promising vaccine design strategy for the continuous development of next-generation SARS-CoV-2 vaccines.
Keywords: NTD loop; Omicron; SARS‐CoV‐2; glycan masking; vaccine.
. 2024 Sep;96(9):e29893.
doi: 10.1002/jmv.29893. Glycan masking of NTD loops with a chimeric RBD of the spike protein as a vaccine design strategy against emerging SARS-CoV-2 Omicron variants
Hao-Chan Hung[SUP] 1 [/SUP], Boon-Fatt Tan[SUP] 2 [/SUP], Wei-Shuo Lin[SUP] 1 [/SUP], Suh-Chin Wu[SUP] 1 3 4 [/SUP]
Affiliations
- PMID: 39192804
- DOI: 10.1002/jmv.29893
The N-terminal domain (NTD) of the SARS-CoV-2 S protein comprises five exposed protruding loops. Deletions, insertions, and substitutions within these NTD loops play a significant role in viral evolution and contribute to immune evasion. We reported previously that introducing the glycan masking mutation R158N/Y160T in the NTD loop led to increased titers of neutralizing antibodies against the SARS-CoV-2 Wuhan-Hu-01 strain, as well as the Alpha, Beta, and Delta variants. In this study, we conducted further investigations on 10 additional glycan-masking sites in the NTD loops. Our findings indicate that the introduction of glycan masking mutations, specifically N87/G89T, H146N/N148T, N185/K187T, and V213N/D215T significantly enhanced neutralizing antibody titers against the Delta variant. The combination of dual glycan-masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N results in a shift toward the Omicron BA.1. Furthermore, the introduction of the Omicron receptor binding domain (RBD) alongside these two dual glycan masking mutations of Wuhan-Hu-1 and XBB.1 NTD sequences resulted in a noticeable shift in antigenic distances, aligning with the Omicron BA.4/5, BA.2.75.2, BQ.1.1, and XBB.1 subvariants on the antigenic map. This strategic combination, which involves the dual glycan masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N in the NTD loops, along with the domain swap incorporating the Omicron RBD, emerges as a promising vaccine design strategy for the continuous development of next-generation SARS-CoV-2 vaccines.
Keywords: NTD loop; Omicron; SARS‐CoV‐2; glycan masking; vaccine.