Dataset Information

Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.

ABSTRACT: The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we used a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduces the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity-matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for antiviral indications would benefit from affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.

SUBMITTER: Zhao F

PROVIDER: S-EPMC9367177 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.

Zhao Fangzhu F Keating Celina C Ozorowski Gabriel G Shaabani Namir N Francino-Urdaniz Irene M IM Barman Shawn S Limbo Oliver O Burns Alison A Zhou Panpan P Ricciardi Michael J MJ Woehl Jordan J Tran Quoc Q Turner Hannah L HL Peng Linghang L Huang Deli D Nemazee David D Andrabi Raiees R Sok Devin D Teijaro John R JR Whitehead Timothy A TA Ward Andrew B AB Burton Dennis R DR Jardine Joseph G JG

iScience 20220811 9

The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we used a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased <i>in vitro</i> functional activity in terms of neutral ...[more]

PMID: 35971553

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Project description:Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

Dataset Information

Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.

Publications

Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.

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