From the Curator-in-Chief's Desk—July 29, 2022

Antibody Evasion by Omicron Variants BA.4 and BA.5

Omicron has fueled the recent global increase of COVID-19 cases. Omicron’s antibody evasion is one reason for this rise in cases, which Dr. Zhengli Shi, Wuhan Institute of Virology, highlighted in this week’s curator commentary. In their article "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, & BA.5," Wang, Q., et al. assessed Omicron sublineages BA.2.12.1 and BA.4/5 against a panel of monoclonal antibodies. The authors described BA.4/5 as "substantially" more resistant to neutralization, mainly because of spike protein substitutions at residues L452 and F486. Shi noted that understanding how spike protein substitutions impact neutralization activity are important for informing future vaccines and treatments. Fortunately, Takashita, E., et al. demonstrated the therapeutic antibody bebtelovimab and antivirals remdesivir, molnupiravir and nirmatrelvir retained activity against BA.4 and BA.5 in The New England Journal of Medicine.

Omicron BA.2.75 Substitutions Affect Immune Evasion

Global SARS-CoV-2 genomic sequencing allows scientists to characterize and plan for new variants. The recently emerged Omicron sublineage BA.2.75 carries more spike protein substitutions than BA.4/5. To understand how these changes affect the immune evasion by BA.2.75, Yamasoba, D., et al. assayed pseudoviruses encoding the BA.2.75 spike protein against monoclonal antibodies in their preprint. The authors reported that therapeutic antibodies regdanvimab, sotrovimab and tixagevimab were functional against BA.2.75, though BA.2.75 appears more resistant to bebtelovimab. In another preprint, Cao, Y., et al. found BA.2.75 shows higher immune evasion than BA.4/5 against sera samples from individuals with past Delta infections, with BA.2.75 having a "distinct" antibody evasion profile compared to BA.4/5. The authors suggested this may account for BA.2.75’s growth advantage in India that experienced high rates of infections caused by the Delta variant. These early data on the BA.2.75 Omicron sublineage support continued surveillance, research and characterization of new variants to plan for public health measures.

Boosters Provide Protection Against Omicron

While Omicron variants evade previous immunity, booster doses of COVID-19 vaccines induce neutralizing antibodies to Omicron. In their preprint, Bhiman, J., et al. observed high titers of neutralizing antibodies against Omicron BA.1 and BA.4 after 3 doses of the Novavax COVID-19 vaccine, which the CDC recently recommended for adults in the U.S. Published in Science, Bowen, J., et al. noted increased neutralizing antibodies and antibody breadth against Omicron sublineages in individuals who received a third homologous or heterologous booster dose regardless of vaccine type. In the future, mucosal boosters could be used to bolster protection to variants. Tang, J., et al. in Science Immunology found addition of a mucosal vaccine encoding the spike protein with a primary mRNA vaccination series induced a strong neutralization of the Omicron BA.1.1 variant in a mouse model. In the meantime, vaccinations in conjunction with masking and testing will help slow the summer spike in cases.

July 29, 2022

By Zhengli Shi, Ph.D., senior scientist, Wuhan Institute of Virology, Chinese Academy of Sciences. Shi is a curator of the registry. 

"Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5" by Wang, Q., et al., published in Nature on July 5, 2022. 
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