Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development.

Cited by papers we hold 12

• Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion · 2024
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• Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans · 2024
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• Spike deep mutational scanning helps predict success of SARS-CoV-2 clades · 2024
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• Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting · 2023
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• Neutralization, effector function and immune imprinting of Omicron variants · 2023
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• Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455–456 synergistically enhances antibody evasion and ACE2 binding · 2023
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• Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies · 2023
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• BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection · 2022
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• Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains · 2022
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• Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination · 2022
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• Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines · 2022
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• Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution · 2022
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