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SARS-CoV-2 pseudovirus strain:XBB.1.5

ABSTRACT: SARS-CoV-2 XBB.1.5 RBD-only pseudovirus based deep mutational scanning libraries

PROVIDER: PRJNA1035795 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26671700.fastq.gz	Fastqsanger.gz
	SRR26671701.fastq.gz	Fastqsanger.gz
	SRR26671702.fastq.gz	Fastqsanger.gz
	SRR26671703.fastq.gz	Fastqsanger.gz
	SRR26671704.fastq.gz	Fastqsanger.gz

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Project description:SARS-CoV-2 Omicron infection results in a milder clinical feature compared to the Delta strain. The development of Omicron specific vaccine has also been hampered due to the low immunogenicity. By reverse-mutating the amino acids in the Omicron receptor binding domain (RBD), we identified that the mutation from Phenylalanine 375 (F375) in the Omicron spike to Serine 375 (S375) in Delta and other early strains significantly enhances the immune response in the manner of vaccines. Interestingly, the new evolution of the 371FAPF375FAF sequence in Omicron exhibited a potent inhibitory effect on macrophage uptake of the RBD nanoparticle or spike-pseudovirus particles. Omicron RBD enhances binding to Siglec-9 on macrophages to reduce the immunogenicity and increase the immune evasion, which could be abrogated by Serine 375 mutation. Based upon these observations, we further developed a bivalent Omicron RBD with S375 mutation and Delta RBD nanoparticle vaccine, which elicited potent and broad neutralizing antibodies in mice, rabbits, and rhesus macaques. Our research suggests that manipulating the Siglec-9 pathway could be a promising approach to enhancing vaccine response. Importantly, our findings suggest that Omicron subvariants have developed a new strategy to evade immune surveillance by impairing the phagocytosis and antigen presentation processes of macrophages.

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