bioRxiv (Cold Spring Harbor Laboratory) · 2022 · 103 citations · 33 references
Veterinary MedicineImmunologyInfectious DiseasesMonoclonal AntibodiesVaccine ImmunologyVaccinologyAntibody CharacterizationAntibody-antigen RecognitionSubunit VaccinesVaccinationVaccines For Emerging PathogensViral VaccinesAntibodiesEvasion Of Antibody Mediated ImmunityNeutralizing Antibody EvasionSars-cov-2 InfectionVaccine-induced Antibody Responses
The BQ and XBB subvariants of SARS‑CoV‑2 Omicron are rapidly expanding, likely because their additional spike mutations enhance antibody evasion. This study evaluates how sera from vaccinated and infected individuals, including those boosted with a WA1/BA.5 bivalent mRNA vaccine, neutralize BQ.1, BQ.1.1, XBB, and XBB.1. Neutralization titers against BQ and XBB subvariants were reduced 13–81‑fold and 66–155‑fold, monoclonal antibodies effective against earlier Omicron were largely inactive, key spike mutations were identified, ACE2 binding remained unchanged, and these variants pose a serious threat to current vaccines and authorized antibodies, potentially driving their population dominance through antibody evasion.
The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
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