Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1...

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Omicron variant (B.1.1.529) emerged rapidly with numerous mutations, designated a variant of concern (VOC).
• Omicron evolved into sublineages BA.1 and BA.2, dominating global SARS-CoV-2 infections.
• Early data indicated reduced neutralizing antibody responses against BA.1 in recovered and vaccinated individuals.

Purpose of the Study:

• To evaluate antibody (immunoglobulin G [IgG]) binding and ACE2 (angiotensin-converting enzyme 2) binding inhibition for Omicron BA.1 and BA.2.
• To compare Omicron variants against other VOCs/variants of interest in a diverse cohort.
• To assess IgG binding dynamics in relation to infection and vaccination status.

Main Methods:

• Assessed IgG binding and ACE2 binding inhibition for Omicron BA.1 and BA.2.
• Utilized a cohort of 352 individuals: convalescent, vaccinated, and infected-then-vaccinated.
• Compared Omicron variants to a panel of other VOCs/variants of interest.

Main Results:

• Omicron variants efficiently bind to ACE2, but elicited antibodies showed reduced binding and ACE2 inhibition compared to wild-type SARS-CoV-2.
• BA.1 demonstrated less IgG binding than BA.2, while BA.2 showed reduced ACE2 binding inhibition.
• Antibody binding to Omicron improved in vaccinated individuals only after a third dose.

Conclusions:

• Omicron BA.1 and BA.2 retain efficient ACE2 binding capability.
• Vaccine/infection-induced antibodies can bind Omicron, but extensive mutations limit strong inhibitory responses.
• Omicron variants exhibit immune evasion, reducing control by pre-existing antibodies.