A multispecific antibody prevents immune escape and confers pan-SARS-CoV-2 neutralization
Misasi, J.; Wei, R. R.; Wang, L.; Pegu, A.; Wei, C.-J.; Oloniniyi, O.; Zhou, T.; Moliva, J. I.; Zhao, B.; Choe, M.; Yang, E. S.; Zhang, Y.; Boruszczak, M.; Chen, M.; Leung, K.; Li, J.; Yang, Z.-Y.; Andersen, H.; Carlton, K.; Godbole, S.; Harris, D. R.; Henry, A. R.; Ivleva, V. B.; Lei, P.; Liu, C.; Longobardi, L.; Merriam, J. S.; Nase, D.; Olia, A. S.; Pessaint, L.; Porto, M.; Shi, W.; Wolff, J. J.; Douek, D. C.; Suthar, M. S.; Gall, J.; Koup, R. A.; Kwong, P. D.; Mascola, J. R.; Nabel, G. J.; Sullivan, N. J.
Show abstract
Summary ParagraphDespite effective countermeasures, SARS-CoV-2 persists worldwide due to its ability to diversify and evade human immunity1. This evasion stems from amino-acid substitutions, particularly in the receptor-binding domain of the spike, that confer resistance to vaccines and antibodies 2-16. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different receptor binding domain (RBD) sites17,18 into multispecific antibodies. Here, we describe multispecific antibodies, including a trispecific that prevented virus escape >3000-fold more potently than the most effective clinical antibody or mixtures of the parental antibodies. Despite being generated before the evolution of Omicron, this trispecific antibody potently neutralized all previous variants of concern and major Omicron variants, including the most recent BA.4/BA.5 strains at nanomolar concentrations. Negative stain electron microscopy revealed that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated inter-spike binding. An optimized trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2 and BA.5, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. Such multispecific antibodies decrease the likelihood of SARS-CoV-2 escape, simplify treatment, and maximize coverage, providing a strategy for universal antibody therapies that could help eliminate pandemic spread for this and other pathogens.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38 97%
- Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals 97%
- Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques 97%
Similar papers in this journal
- Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease 97%
- Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus glycoprotein complex 97%
- Protein design for evaluating vaccines against future viral variation 97%
Similar papers in this journal
- Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains 98%
- Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients 98%
- Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad Neuraminidase Inhibition by Human Antibodies 97%
Similar papers in this journal
- Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike 98%
- A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron 98%
- Potently neutralizing human antibodies that block SARS-CoV-2 receptor binding and protect animals 98%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.