Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Hastie, Kathryn M.; Li, Haoyang; Bedinger, Daniel; Schendel, Sharon L.; Dennison, S. Moses; Li, Kan; Rayaprolu, Vamseedhar; Yu, Xiaoying; Mann, Colin; Zandonatti, Michelle; Avalos, Ruben Diaz; Zyla, Dawid; Buck, Tierra; Hui, Sean; Shaffer, Kelly; Hariharan, Chitra; Yin, Jieyun; Olmedillas, Eduardo; Enriquez, Adrian; Parekh, Diptiben; Abraha, Milite; Feeney, Elizabeth Ann; Horn, Gillian Q.; team, CoVIC-DB; Aldon, Yoann; Ali, Hanif; Aracic, Sanja; Cobb, Ronald R.; Federman, Ross S.; Fernandez, Joseph; Glanville, Jacob; Green, Robin; Grigoryan, Gevorg; Hernández, Ana González; Ho, David D.; Huang, Kuan-Ying A.; Ingraham, John L.; Jiang, Weidong; Kellam, Paul; Kim, Cheol-Min; Kim, Min‐Soo; Kim, Hyeong Mi; Kong, Chao; Krebs, Shelly J.; Lan, Fei; Lang, Guo-Jun; Lee, Soo Young; Leung, Cheuk Lun; Liu, Junli; Lu, Yuele; MacCamy, Anna J.; McGuire, Andrew T.; Palser, Anne L.; Rabbitts, Terence H.; Tehrani, Zahra Rikhtegaran; Sajadi, Mohammad M.; Sanders, Rogier W.; Sato, Aaron K.; Schweizer, Liang; Seo, Ji-Min; Shen, Bingqing; Snitselaar, Jonne L.; Stamatatos, Leonidas; Tan, Yongcong; Tomic, Milan T.; Gils, Marit J. van; Youssef, Sawsan; Yu, Jian; Yuan, Tom Z.; Zhang, Qian; Peters, Bjoern; Tomaras, Georgia D.; Germann, Timothy C.; Saphire, Erica Ollmann

doi:10.1126/science.abh2315

Cited by 242 publications

(294 citation statements)

References 59 publications

(76 reference statements)

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“…Sites under selection are distributed over the entire spike protein, the S1 region containing NTD and RBD, which was observed to harbor a maximum number of sites under selection (Figure 6a,b) and significantly variable sites. These two domains are functionally important not only for maintaining a trimer conformation of spike and mediating host-receptor interactions but also as a predominant antigenic region with evidence for several monoclonal and polyclonal antibody binding sites, neutralizing sites as well as CD4 and CD8-responsive regions [60,61]. The variable sites N439K and Y453F, L455F and E484K are known to escape neutralization by therapeutic antibodies REGN10987 and REGN10933, respectively [62][63][64].…”

Section: Discussionmentioning

confidence: 99%

Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

Limaye

Kasibhatla

Ramtirthkar

et al. 2021

Viruses

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The COVID-19 pandemic is a global challenge that impacted 200+ countries. India ranks in the second and third positions in terms of number of reported cases and deaths. Being a populous country with densely packed cities, SARS-CoV-2 spread exponentially. India sequenced ≈0.14% isolates from confirmed cases for pandemic surveillance and contributed ≈1.58% of complete genomes sequenced globally. This study was designed to map the circulating lineage diversity and to understand the evolution of SARS-CoV-2 in India using comparative genomics and population genetics approaches. Despite varied sequencing coverage across Indian States and Union Territories, isolates belonging to variants of concern (VoC) and variants of interest (VoI) circulated, persisted, and diversified during the first seventeen months of the pandemic. Delta and Kappa lineages emerged in India and spread globally. The phylogenetic tree shows lineage-wise monophyletic clusters of VoCs/VoIs and diversified tree topologies for non-VoC/VoI lineages designated as ‘Others’ in this study. Evolutionary dynamics analyses substantiate a lack of spatio-temporal clustering, which is indicative of multiple global and local introductions. Sites under positive selection and significant variations in spike protein corroborate with the constellation of mutations to be monitored for VoC/VoI as well as substitutions that are characteristic of functions with implications in virus–host interactions, differential glycosylation, immune evasion, and escape from neutralization.

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Section: Discussionmentioning

confidence: 99%

Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

Limaye

Kasibhatla

Ramtirthkar

et al. 2021

Viruses

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“…The Coronavirus Immunotherapy Consortium (CoVIC) ( 47 ) was launched to evaluate potential therapeutic antibodies in side-by-side in vitro analyses using standardized platform assays and in vivo models. Findings from these comparative studies are used to create a profile of antibody activity that correlates with protective clinical efficacy and predicts clinically successful outcomes ( 47 , 48 ).…”

Section: Session 1 Key Theme: Characterization Of Functional Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

“…To date, CoVIC has compiled 350 candidate therapeutics from more than 50 groups in academia, research institutions, industry and biotechnology companies, and government agencies ( 47 , 48 ). These antibodies are evaluated by 8 partner laboratories according to CoVIC standardized testing protocols; CoVIC also assesses the ability of their compiled antibodies to retain their neutralizing activity to the VOCs ( 47 , 48 ).…”

Section: Session 1 Key Theme: Characterization Of Functional Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

Update on and Future Directions for Use of Anti–SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19

et al. 2022

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“…The list of these variants of concern (VOCs) consist of B.1.1.7 (Alpha), B.1.351 (Beta), B.1.1.28/P.1 (Gamma) and B.1.617.2 (Delta) variants (November 2021, WHO). The reduction of neutralization by antibodies is caused by mutations in S glycoprotein, including K417N/T, L452R, T478K, E484K and N501Y substitutions (15, 16). In this regard, it became necessary to isolate antibodies, the neutralizing activity of which will not be affected due to observed mutations, therefore, these antibodies or their cocktails will retain activity against each of VOCs.…”

Section: Introductionmentioning

confidence: 99%

Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern, including Omicron variant

Favorskaya

Shcheblyakov

Esmagambetov

et al. 2021

Preprint

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Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma and Delta variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.

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Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Cited by 242 publications

References 59 publications

Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

Update on and Future Directions for Use of Anti–SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19

Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern, including Omicron variant

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