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Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.

<div class='caption-title'>Identification of potential antibodies against a broader array of variants.</div>
<div class='caption-title'>MAbs binding and neutralization of diverse SARS-CoV-2 variants.</div>
<div class='caption-title'>Cryo-EM of Delta Spike Trimer with BA7208-Fab/BA7125-Fab.</div>
Wang Y, Yan A, Song D, Dong C, Rao M, Gao Y, Qi R, Ma X, Wang Q, Xu H, Liu H, Han J, Duan M, Liu S, Yu X, Zong M, Feng J, Jiao J, Zhang H, Li M, Yu B, Wang Y, Meng F, Ni X, Li Y, Shen Z, Sun B, Shao X, Zhao H, Zhao Y, Li R, Zhang Y, Du G, Lu J, You C, Jiang H, Zhang L, Wang L, Dou C, Liu Z, Zhao J
OpenAccess logo Cell Discov 9 3 (2023)
Related entries: 7xda, 7xdb, 7xdk, 7xdl

Cited: 9 times
EuropePMC logo PMID: 36609558

Abstract

SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1-BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.

Reviews citing this publication (2)

  1. Broadly neutralizing antibodies against COVID-19. Zhou D, Ren J, Fry EE, Stuart DI. Curr Opin Virol 61 101332 (2023)
  2. Biparatopic antibodies: therapeutic applications and prospects. Niquille DL, Fitzgerald KM, Gera N. MAbs 16 2310890 (2024)

Articles citing this publication (7)

  1. Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages. Marcotte H, Cao Y, Zuo F, Simonelli L, Sammartino JC, Pedotti M, Sun R, Cassaniti I, Hagbom M, Piralla A, Yang J, Du L, Percivalle E, Bertoglio F, Schubert M, Abolhassani H, Sherina N, Guerra C, Borte S, Rezaei N, Kumagai-Braesch M, Xue Y, Su C, Yan Q, He P, Grönwall C, Klareskog L, Calzolai L, Cavalli A, Wang Q, Robbiani DF, Hust M, Shi Z, Feng L, Svensson L, Chen L, Bao L, Baldanti F, Xiao J, Qin C, Hammarström L, Yang X, Varani L, Xie XS, Pan-Hammarström Q. Proc Natl Acad Sci U S A 121 e2315354120 (2024)
  2. Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides. Parisi G, Piacentini R, Incocciati A, Bonamore A, Macone A, Rupert J, Zacco E, Miotto M, Milanetti E, Tartaglia GG, Ruocco G, Boffi A, Di Rienzo L. Front Mol Biosci 10 1332359 (2023)
  3. Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants. Wang Y, Yan A, Song D, Duan M, Dong C, Chen J, Jiang Z, Gao Y, Rao M, Feng J, Zhang Z, Qi R, Ma X, Liu H, Yu B, Wang Q, Zong M, Jiao J, Xing P, Pan R, Li D, Xiao J, Sun J, Li Y, Zhang L, Shen Z, Sun B, Zhao Y, Zhang L, Dai J, Zhao J, Wang L, Dou C, Liu Z, Zhao J. Nat Commun 15 842 (2024)
  4. Nebulization of pharmacological solutions with an innovative medical device based on microvaporization. Brandimarte B, Di Rienzo Businco L, Cappello F, Fiore R, Bastone G, Gualdi G, Sollaku S, Casciani E, Tortorella F, Longo P, Centanini E, Pavaci S, Sangiuolo F, Patrizi MP, Miersch S, Sidhu SS, Sacchini V, Novelli G. Heliyon 9 e14673 (2023)
  5. A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses. Wang Y, Hao A, Ji P, Ma Y, Zhang Z, Chen J, Mao Q, Xiong X, Rehati P, Wang Y, Wang Y, Wen Y, Lu L, Chen Z, Zhao J, Wu F, Huang J, Sun L. Nat Commun 15 5127 (2024)
  6. Engineered Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2 Omicron Subvariants BA.1, BA.4/5, XBB.1 and BQ.1.1. Wang J, Shi B, Chen H, Yu M, Wang P, Qian Z, Hu K, Wang J. Vaccines (Basel) 12 417 (2024)
  7. The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine. Chen X, Mohapatra A, Nguyen HTV, Schimanski L, Kit Tan T, Rijal P, Chen CP, Cheng SH, Lee WH, Chou YC, Townsend AR, Ma C, Huang KA. PLoS Pathog 20 e1012246 (2024)


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