Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

{ 'institution': [{'name': 'bioRxiv'}], 'indexed': { 'date-parts': [[2022, 11, 22]], 'date-time': '2022-11-22T05:55:25Z', 'timestamp': 1669096525819}, 'posted': {'date-parts': [[2022, 11, 17]]}, 'group-title': 'Microbiology', 'reference-count': 63, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2022, 11, 21]]}, 'abstract': '<jats:p>Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to ' 'the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The ' 'subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in ' 'November 2022. They carry an additional and often redundant set of mutations in the spike, ' 'likely responsible for increased transmissibility and immune evasion. Here, we established a ' 'viral amplification procedure to easily isolate Omicron strains. We examined their ' 'sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer ' 'BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. ' 'Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any ' 'antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly ' 'active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated ' 'individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A ' 'BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower ' 'against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection ' 'increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. ' 'Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in ' 'immunized populations and raises concerns about the efficacy of most currently available ' 'mAbs.</jats:p>', 'DOI': '10.1101/2022.11.17.516888', 'type': 'posted-content', 'created': { 'date-parts': [[2022, 11, 17]], 'date-time': '2022-11-17T21:35:16Z', 'timestamp': 1668720916000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies', 'prefix': '10.1101', 'author': [ {'given': 'Delphine', 'family': 'Planas', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3952-4261', 'authenticated-orcid': False, 'given': 'Timothee', 'family': 'Bruel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Isabelle', 'family': 'Staropoli', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Florence', 'family': 'Guivel-Benhassine', 'sequence': 'additional', 'affiliation': []}, {'given': 'Francoise', 'family': 'Porrot', 'sequence': 'additional', 'affiliation': []}, {'given': 'Piet', 'family': 'Maes', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1298-7565', 'authenticated-orcid': False, 'given': 'Ludivine', 'family': 'Grzelak', 'sequence': 'additional', 'affiliation': []}, {'given': 'Matthieu', 'family': 'Prot', 'sequence': 'additional', 'affiliation': []}, {'given': 'Said', 'family': 'Mougari', 'sequence': 'additional', 'affiliation': []}, {'given': 'Cyril', 'family': 'Planchais', 'sequence': 'additional', 'affiliation': []}, {'given': 'Julien', 'family': 'Puech', 'sequence': 'additional', 'affiliation': []}, {'given': 'Madelina', 'family': 'Saliba', 'sequence': 'additional', 'affiliation': []}, {'given': 'Riwan', 'family': 'Sahraoui', 'sequence': 'additional', 'affiliation': []}, {'given': 'Florent', 'family': 'Femy', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nathalie', 'family': 'Morel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jeremy', 'family': 'Dufloo', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1844-545X', 'authenticated-orcid': False, 'given': 'Rafael', 'family': 'Sanjuan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hugo', 'family': 'Mouquet', 'sequence': 'additional', 'affiliation': []}, {'given': 'Emmanuel', 'family': 'Andre', 'sequence': 'additional', 'affiliation': []}, {'given': 'Laurent', 'family': 'Hocqueloux', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-8420-7743', 'authenticated-orcid': False, 'given': 'Etienne', 'family': 'Simon-Loriere', 'sequence': 'additional', 'affiliation': []}, {'given': 'David', 'family': 'Veyer', 'sequence': 'additional', 'affiliation': []}, {'given': 'Thierry', 'family': 'Prazuck', 'sequence': 'additional', 'affiliation': []}, {'given': 'Helene', 'family': 'Pere', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0729-1475', 'authenticated-orcid': False, 'given': 'Olivier', 'family': 'Schwartz', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2022111910400671000_2022.11.17.516888v1.1', 'doi-asserted-by': 'crossref', 'first-page': '679', 'DOI': '10.1038/s41586-022-04411-y', 'article-title': 'Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern ' 'Africa', 'volume': '603', 'year': '2022', 'journal-title': 'Nature'}, { 'key': '2022111910400671000_2022.11.17.516888v1.2', 'doi-asserted-by': 'crossref', 'first-page': '1785', 'DOI': '10.1038/s41591-022-01911-2', 'article-title': 'Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa', 'volume': '28', 'year': '2022', 'journal-title': 'Nature Medicine'}, { 'key': '2022111910400671000_2022.11.17.516888v1.3', 'doi-asserted-by': 'crossref', 'first-page': '417', 'DOI': '10.1016/S0140-6736(22)00100-3', 'article-title': 'COVID-19 will continue but 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