PT  - JOURNAL ARTICLE
AU  - Panke Qu
AU  - Julia N. Faraone
AU  - John P. Evans
AU  - Yi-Min Zheng
AU  - Claire Carlin
AU  - Mirela Anghelina
AU  - Patrick Stevens
AU  - Soledad Fernandez
AU  - Daniel Jones
AU  - Ashish Panchal
AU  - Linda J. Saif
AU  - Eugene M. Oltz
AU  - Kai Xu
AU  - Richard J. Gumina
AU  - Shan-Lu Liu
TI  - Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants
AID  - 10.1101/2023.01.16.524244
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.16.524244
4099  - http://biorxiv.org/content/early/2023/01/17/2023.01.16.524244.short
4100  - http://biorxiv.org/content/early/2023/01/17/2023.01.16.524244.full
AB  - Newly emerging Omicron subvariants continue to emerge around the world, presenting potential challenges to current vaccination strategies. This study investigates the extent of neutralizing antibody escape by new subvariants XBB.1.5, CH.1.1, and CA.3.1, as well as their impacts on spike protein biology. Our results demonstrated a nearly complete escape of these variants from neutralizing antibodies stimulated by three doses of mRNA vaccine, but neutralization was rescued by a bivalent booster. However, CH.1.1 and CA.3.1 variants were highly resistant to both monovalent and bivalent mRNA vaccinations. We also assessed neutralization by sera from individuals infected during the BA.4/5 wave of infection and observed similar trends of immune escape. In these cohorts, XBB.1.5 did not exhibit enhanced neutralization resistance over the recently dominant BQ.1.1 variant. Notably, the spike proteins of XBB.1.5, CH.1.1, and CA.3.1 all exhibited increased fusogenicity compared to BA.2, correlating with enhanced S processing. Overall, our results support the administration of new bivalent mRNA vaccines, especially in fighting against newly emerged Omicron subvariants, as well as the need for continued surveillance of Omicron subvariants.Competing Interest StatementThe authors have declared no competing interest.