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Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

ABSTRACT: On the 24 ^th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

SUBMITTER: Dejnirattisai W

PROVIDER: S-EPMC8722586 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

Dejnirattisai Wanwisa W Huo Jiandong J Zhou Daming D Zahradník Jiří J Supasa Piyada P Liu Chang C Duyvesteyn Helen M E HME Ginn Helen M HM Mentzer Alexander J AJ Tuekprakhon Aekkachai A Nutalai Rungtiwa R Wang Beibei B Dijokaite Aiste A Khan Suman S Avinoam Ori O Bahar Mohammad M Skelly Donal D Adele Sandra S Johnson Sile Ann SA Amini Ali A Ritter Thomas T Mason Chris C Dold Christina C Pan Daniel D Assadi Sara S Bellass Adam A Omo-Dare Nikki N Koeckerling David D Flaxman Amy A Jenkin Daniel D Aley Parvinder K PK Voysey Merryn M Clemens Sue Ann Costa SAC Naveca Felipe Gomes FG Nascimento Valdinete V Nascimento Fernanda F Fernandes da Costa Cristiano C Resende Paola Cristina PC Pauvolid-Correa Alex A Siqueira Marilda M MM Baillie Vicky V Serafin Natali N Ditse Zanele Z Da Silva Kelly K Madhi Shabir S Nunes Marta C MC Malik Tariq T Openshaw Peter Jm PJ Baillie J Kenneth JK Semple Malcolm G MG Townsend Alain R AR Huang Kuan-Ying A KA Tan Tiong Kit TK Carroll Miles W MW Klenerman Paul P Barnes Eleanor E Dunachie Susanna J SJ Constantinides Bede B Webster Hermione H Crook Derrick D Pollard Andrew J AJ Lambe Teresa T Paterson Neil G NG Williams Mark A MA Hall David R DR Fry Elizabeth E EE Mongkolsapaya Juthathip J Ren Jingshan J Schreiber Gideon G Stuart David I DI Screaton Gavin R GR

bioRxiv : the preprint server for biology 20211222

On the 24 <sup>th</sup> November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vac ...[more]

PMID: 34981049

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Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies.MethodsFour nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods.ResultsThree of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 μg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 μg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary.ConclusionOur study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.

Dataset Information

Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

Publications

Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

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