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Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.
<div class='caption-title'>Utilizing antibody avidity effects suggests a strategy to target antibodies to conserved regions of sarbecovirus RBDs</div>
<div class='caption-title'>A subset of mAbs elicited in mosaic-8 and homotypic SARS-CoV-2 RBD nanoparticle-immunized mice show cross-reactive binding and neutralization properties</div>
Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ
OpenAccess logo Immunity (2022)
Related entries: 7uz4, 7uz5, 7uz7, 7uz8, 7uz9, 7uza, 7uzb, 7uzc, 7uzd

Cited: 14 times
EuropePMC logo PMID: 36370711

Abstract

Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

Articles - 7uz6 mentioned but not cited (1)

  1. Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes. Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ. Immunity 55 2419-2435.e10 (2022)


Reviews citing this publication (4)

  1. Bringing immunofocusing into focus. Musunuri S, Weidenbacher PAB, Kim PS. NPJ Vaccines 9 11 (2024)
  2. In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms. Cankat S, Demael MU, Swadling L. Cell Mol Immunol 21 103-118 (2024)
  3. SARS-CoV-2 S Glycoprotein Stabilization Strategies. Pedenko B, Sulbaran G, Guilligay D, Effantin G, Weissenhorn W. Viruses 15 558 (2023)
  4. Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19. Ren Z, Shen C, Peng J. Viruses 15 1297 (2023)

Articles citing this publication (9)

  1. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Cohen AA, van Doremalen N, Greaney AJ, Andersen H, Sharma A, Starr TN, Keeffe JR, Fan C, Schulz JE, Gnanapragasam PNP, Kakutani LM, West AP, Saturday G, Lee YE, Gao H, Jette CA, Lewis MG, Tan TK, Townsend AR, Bloom JD, Munster VJ, Bjorkman PJ. Science 377 eabq0839 (2022)
  2. Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein. Bianchini F, Crivelli V, Abernathy ME, Guerra C, Palus M, Muri J, Marcotte H, Piralla A, Pedotti M, De Gasparo R, Simonelli L, Matkovic M, Toscano C, Biggiogero M, Calvaruso V, Svoboda P, Cervantes Rincón T, Fava T, Podešvová L, Shanbhag AA, Celoria A, Sgrignani J, Stefanik M, Hönig V, Pranclova V, Michalcikova T, Prochazka J, Guerrini G, Mehn D, Ciabattini A, Abolhassani H, Jarrossay D, Uguccioni M, Medaglini D, Pan-Hammarström Q, Calzolai L, Fernandez D, Baldanti F, Franzetti-Pellanda A, Garzoni C, Sedlacek R, Ruzek D, Varani L, Cavalli A, Barnes CO, Robbiani DF. Sci Immunol 8 eade0958 (2023)
  3. An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design. Sheng Z, Bimela JS, Wang M, Li Z, Guo Y, Ho DD. Front Immunol 14 1190416 (2023)
  4. Broadly neutralizing aptamers to SARS-CoV-2: A diverse panel of modified DNA antiviral agents. Gelinas AD, Tan TK, Liu S, Jaramillo JG, Chadwick J, Harding AC, Zhang C, Ream BE, Chase CN, Otis MR, Lee T, Schneider DJ, James WS, Janjic N. Mol Ther Nucleic Acids 31 370-382 (2023)
  5. Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens. Mabrouk MT, Zidan AA, Aly N, Mohammed MT, Ghantous F, Seaman MS, Lovell JF, Nasr ML. Vaccines (Basel) 11 1655 (2023)
  6. Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron. Hao L, Hsiang TY, Dalmat RR, Ireton R, Morton JF, Stokes C, Netland J, Hale M, Thouvenel C, Wald A, Franko NM, Huden K, Chu HY, Sigal A, Greninger AL, Tilles S, Barrett LK, Van Voorhis WC, Munt J, Scobey T, Baric RS, Rawlings DJ, Pepper M, Drain PK, Gale M. Viruses 15 530 (2023)
  7. Heteromultimeric sarbecovirus receptor binding domain immunogens primarily generate variant-specific neutralizing antibodies. Zang T, Osei Kuffour E, Baharani VA, Canis M, Schmidt F, Da Silva J, Lercher A, Chaudhary P, Hoffmann HH, Gazumyan A, Miranda IC, MacDonald MR, Rice CM, Nussenzweig MC, Hatziioannou T, Bieniasz PD. Proc Natl Acad Sci U S A 120 e2317367120 (2023)
  8. Meta-Analysis SARS-CoV-2 neutralizing antibody bebtelovimab - a systematic scoping review and meta-analysis. Liew MNY, Kua KP, Lee SWH, Wong KK. Front Immunol 14 1100263 (2023)
  9. Targets and cross-reactivity of human T cell recognition of common cold coronaviruses. Tarke A, Zhang Y, Methot N, Narowski TM, Phillips E, Mallal S, Frazier A, Filaci G, Weiskopf D, Dan JM, Premkumar L, Scheuermann RH, Sette A, Grifoni A. Cell Rep Med 4 101088 (2023)


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