Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity

Shrock, Ellen; Fujimura, Eric; Kula, Tomasz; Timms, Richard T.; Lee, I-Hsiu; Leng, Yumei; Robinson, Matthew L.; Sie, Brandon M.; Li, Mamie Z.; Chen, Yuezhou; Logue, Jennifer K.; Zuiani, Adam; McCulloch, Denise J.; Lelis, Felipe; Henson, Stephanie N.; Monaco, Daniel R.; Travers, Meghan; Habibi, Shaghayegh; Clarke, William; Caturegli, Patrizio; Laeyendecker, Oliver; Piechocka-Trocha, Alicja; Li, Jonathan Z.; Khatri, Ashok; Chu, Helen Y.; Villani, Alexandra‐Chloé; Kays, Kyle R.; Goldberg, Marcia B.; Hacohen, Nir; Filbin, Michael R.; Yu, Xu G.; Walker, Bruce D.; Wesemann, Duane R.; Larman, H. Benjamin; Lederer, James A.; Elledge, Stephen J.; Lavin-Parsons, Kendall M.; Parry, Blair A.; Lilley, Brendan M.; Lodenstein, Carl L.; McKaig, Brenna; Charland, Nicole C.; Khanna, Hargun K.; Margolin, Justin D.; Gonye, Anna L.K.; Gushterova, Irena; LaSalle, Thomas J.; Sharma, Nihaarika; Russo, Brian C.; Rojas-López, Maricarmen; Sade-Feldman, Moshe; Manakongtreecheep, Kasidet; Tantivit, Jessica; Thomas, Molly; Abayneh, Betelihem A.; Allen, Patrick; Antille, Diane; Armstrong, Katrina; Boyce, Siobhan; Braley, Joan; Branch, Kelley R.; Broderick, Katherine; Carney, Julia; Chan, Andrew; Davidson, Susan; Dougan, Michael; Drew, David A.; Elliman, Ashley; Flaherty, Keith T.; Flannery, Jeanne; Forde, Pamela; Gettings, Elise; Griffin, Amanda; Grimmel, Sheila; Grinke, Kathleen; Hall, Kathryn; Healy, Meg; Henault, Deborah; Holland, Grace; Kayitesi, Chantal; LaValle, Vlasta; Lu, Yuting; Luthern, Sarah; Marchewka, Jordan; Martino, Brittani; McNamara, Roseann; Nambu, Christian; Nelson, Susan C.; Noone, Marjorie; Ommerborn, Christine; Pacheco, Lois Chris; Phan, Nicole; Porto, Falisha A.; Ryan, Edward T.; Selleck, Kathleen; Slaughenhaupt, Sue; Sheppard, Kimberly Smith; Suschana, Elizabeth; Wilson, Vivine; Alter, Galit; Balazs, Alejandro; Bals, Julia; Barbash, Max; Bartsch, Yannic C.; Boucau, Julie; Chevalier, Josh; Chowdhury, Fatema Z.; Einkauf, Kevin; Fallon, Jon; Fedirko, Liz; Finn, Kelsey; García-Broncano, Pilar; Hartana, Ciputra Adijaya; Jiang, Chenyang; Kapłonek, Paulina; Karpell, Marshall; Lam, Evan C.; Lefteri, Kristina; Lian, Xiaodong; Lichterfeld, Mathias; Lingwood, Daniel; Liu, Huan; Liu, Jinqing; Ly, Natasha; Michell, Ashlin; Millstrom, Ilan; Miranda, Noah; O’Callaghan, Claire; Osborn, Matthew; Pillai, Shiv; Rassadkina, Yelizaveta; Reissis, Alexandra; Ruzicka, Francis F.; Seiger, Kyra; Sessa, Libera; Sharr, Christianne; Shin, Sally; Singh, Nishant K.; Sun, Weiwei; Sun, Xiaoming; Ticheli, Hannah; Trocha-Piechocka, Alicja; Worrall, Daniel; Zhu, Alex; Daley, George Q.; Golan, David; Heller, Howard M.; Sharpe, Arlene; Jilg, Nikolaus; Rosenthal, Alex; Wong, C. Jason

doi:10.1126/science.abd4250

Cited by 610 publications

(898 citation statements)

References 39 publications

Supporting

Mentioning

802

Contrasting

Unclassified

Order By: Relevance

“…2A). As IgG and IgA are the most abundant isotypes in blood 53 APGQTGKIADYNYKLPDDFT' for horse (Fig. 3A); 'YQPYRVVVLSFELLH' and 'CVNFNFNGL' for mouse (Fig.…”

Section: Characterization Of the 18 Linear B-cell Epitopes Selected Wmentioning

confidence: 99%

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Zhao

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

show abstract

“…2A). As IgG and IgA are the most abundant isotypes in blood 53 APGQTGKIADYNYKLPDDFT' for horse (Fig. 3A); 'YQPYRVVVLSFELLH' and 'CVNFNFNGL' for mouse (Fig.…”

Section: Characterization Of the 18 Linear B-cell Epitopes Selected Wmentioning

confidence: 99%

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Zhao

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…T14I mutation is also present in peptides predicted as HLA Class I T cell epitopes. 12 M: D3G and N: S194L mutations are present in antibody epitopes, 16 which may reduce antibody avidity. Mutation effects can contribute to immunomodulation that increases CFR, because innate immune system depression, 37 adaptive immune system dysregulation, 38 and incoordination between cell-mediated and humoral immunity 39 underlie the exacerbation of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we also found that mutations associated with higher prevalence, such as ORF1a: I300F (nsp2), ORF1a: H1113Y (nsp3), ORF1b: A1844V (nsp14), S: T307I; ORF6: I33T, N: A12G/ORF9b: H9D, N: S197L, and N: A220V, are present in antibody epitopes. 16 ORF6: I33T is also located in a HLA-DR T cell epitope. 36 The high prevalence among NHB and Hispanics has been attributed to living in densely populated areas.…”

Section: Discussionmentioning

confidence: 99%

“…There are many national parks near Native American settlements, and people in such areas may have immunity that had been induced by exposure to microorganisms such as animal-derived viruses. 16 Indeed, the areas of national parks in the US states were negatively correlated with the CFR and mortality of SARS-CoV-2 (Table 1). However, MRA showed less contribution than Native Americans, suggesting that the presence of national parks alone cannot explain the decline in CFR and mortality.…”

Section: United Statesmentioning

confidence: 97%

See 1 more Smart Citation

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

Takahashi

Kamikubo

Hattori

2020

Preprint

View full text Add to dashboard Cite

The world has been plagued by complex waves of SARS-CoV-2 epidemics that vary from region to region, leaving the end of the pandemic unpredictable. Here we performed "genetic fingerprinting" to compare the local viral genotypes with epidemiological information and reveal the molecular dynamics of the SARS-CoV-2 epidemic worldwide. A multifaceted analyses of the epidemic trends and their relationship to virus genotypes, regional herd immunity, population density, and race has shown that epidemic outcomes are affected by: (1) Increased fitness of the virus due to mutations of viral proteins; (2) Immunity against previously prevalent subtypes that prevents or exacerbates COVID-19; (3) Immune evasion due to viral mutations; (4) Viral competition with coexisting subtypes; (5) Dense and crowded living environment; (6) Racial and social disparities; (7) Upper limit of viral mutations that enable natural selection. These findings provide an overview of the current epidemic, help predict the future, and develop effective countermeasures.

show abstract

“…Further research has revealed that even people who have not been infected with the virus can have antibodies 3 and T cells 2 that recognize SARS-CoV-2. This might be the result of people having previously been infected with related coronaviruses that cause the common cold.…”

Section: The Immunity Challengementioning

confidence: 99%

Why decoding the immune response to COVID matters for vaccines

2020

Nature

View full text Add to dashboard Cite

the consensus among clinicians and researchers is that the FDA's decision was premature, because not all these antibodies will be protective. There is not yet definitive evidence that this treatment is effective 4 , although trials are ongoing to explore whether convalescent plasma from people with high levels of neutralizing antibodies against the virus might be beneficial in the treatment of severe COVID-19. A more promising approach than convalescent plasma would be to isolate specific and potent neutralizing antibodies from infected patients, and to develop antibody treatments based on these. This approach has been successful for other viral diseases: just last week, the FDA approved one such treatment for Ebola virus. And trials are under way to test the effectiveness of such monoclonal antibodies against COVID-19. How likely is reinfection? Another urgent question is whether a person who has recovered from COVID-19 is protected from future Nature's second pandemic progress report A detailed understanding of immunity is key to developing safe and effective vaccines.

show abstract

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity

Cited by 610 publications

References 39 publications

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

Why decoding the immune response to COVID matters for vaccines

Contact Info

Product

Resources

About