Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation

• Published in: The Lancet infectious diseases Vol. 22; no. 12; pp. 1666 - 1668
• Main Authors: Wang, Qian, Li, Zhiteng, Ho, Jerren, Guo, Yicheng, Yeh, Andre Yanchen, Mohri, Hiroshi, Liu, Michael, Wang, Maple, Yu, Jian, Shah, Jayesh G, Chang, Jennifer Y, Herbas, Favio, Yin, Michael T, Sobieszczyk, Magdalena E, Sheng, Zizhang, Liu, Lihong, Ho, David D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.12.2022; Elsevier Limited
• Subjects: ACE2; Affinity; Angiotensin-converting enzyme 2; Antibodies; Antibodies, Viral; Coronaviruses; Correspondence; COVID-19; Disease transmission; Humans; Immunoglobulins; Infectious diseases; Inventors; Monoclonal antibodies; mRNA; Mutation; Pandemics; Patent applications; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccination
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(22)00694-6

All the spike proteins from BA.4/5 sublineages, and those of BA.4/5 carrying point mutations of R346S and N658S, showed similar binding affinities to ACE2, with dissociation constant values ranging 0·39–0·49 nM. [...]the expansion of BA.4.6 cannot be explained by a higher affinity for human ACE2. Next, to investigate the antibody evasion properties of BA.4.6, BA.4.7, BA.5.9, and BF.7, we assessed the sensitivity of their corresponding pseudoviruses to neutralisation with serum samples from healthy individuals who had received three doses of a COVID-19 mRNA vaccine BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna; ie, who had received booster doses) and patients with either BA.1, BA.2, or BA.4/5 breakthrough infection after vaccination (figure; appendix p 1). JY, LL, and DDH are inventors on patent applications (WO2021236998) or provisional patent applications (63/271,627) filed by Columbia University for a number of SARS-CoV-2 neutralising antibodies described in this Correspondence; both sets of applications are under review.