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2. Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

Author

Wang, Qian, Guo, Yicheng, Liu, Liyuan, Schwanz, Logan T., Li, Zhiteng, Nair, Manoj S., Ho, Jerren, Zhang, Richard M., Iketani, Sho, Yu, Jian, Huang, Yiming, Qu, Yiming, Valdez, Riccardo, Lauring, Adam S., Huang, Yaoxing, Gordon, Aubree, Wang, Harris H., Liu, Lihong, and Ho, David D.

Published
2023
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3. Author Correction: Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Author

Han, Yuling, Duan, Xiaohua, Yang, Liuliu, Nilsson-Payant, Benjamin E., Wang, Pengfei, Duan, Fuyu, Tang, Xuming, Yaron, Tomer M., Zhang, Tuo, Uhl, Skyler, Bram, Yaron, Richardson, Chanel, Zhu, Jiajun, Zhao, Zeping, Redmond, David, Houghton, Sean, Nguyen, Duc-Huy T., Xu, Dong, Wang, Xing, Jessurun, Jose, Borczuk, Alain, Huang, Yaoxing, Johnson, Jared L., Liu, Yuru, Xiang, Jenny, Wang, Hui, Cantley, Lewis C., tenOever, Benjamin R., Ho, David D., Pan, Fong Cheng, Evans, Todd, Chen, Huanhuan Joyce, Schwartz, Robert E., and Chen, Shuibing

Published
2024
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7. Defining the risk of SARS-CoV-2 variants on immune protection

Author

DeGrace, Marciela M, Ghedin, Elodie, Frieman, Matthew B, Krammer, Florian, Grifoni, Alba, Alisoltani, Arghavan, Alter, Galit, Amara, Rama R, Baric, Ralph S, Barouch, Dan H, Bloom, Jesse D, Bloyet, Louis-Marie, Bonenfant, Gaston, Boon, Adrianus CM, Boritz, Eli A, Bratt, Debbie L, Bricker, Traci L, Brown, Liliana, Buchser, William J, Carreño, Juan Manuel, Cohen-Lavi, Liel, Darling, Tamarand L, Davis-Gardner, Meredith E, Dearlove, Bethany L, Di, Han, Dittmann, Meike, Doria-Rose, Nicole A, Douek, Daniel C, Drosten, Christian, Edara, Venkata-Viswanadh, Ellebedy, Ali, Fabrizio, Thomas P, Ferrari, Guido, Fischer, Will M, Florence, William C, Fouchier, Ron AM, Franks, John, García-Sastre, Adolfo, Godzik, Adam, Gonzalez-Reiche, Ana Silvia, Gordon, Aubree, Haagmans, Bart L, Halfmann, Peter J, Ho, David D, Holbrook, Michael R, Huang, Yaoxing, James, Sarah L, Jaroszewski, Lukasz, Jeevan, Trushar, Johnson, Robert M, Jones, Terry C, Joshi, Astha, Kawaoka, Yoshihiro, Kercher, Lisa, Koopmans, Marion PG, Korber, Bette, Koren, Eilay, Koup, Richard A, LeGresley, Eric B, Lemieux, Jacob E, Liebeskind, Mariel J, Liu, Zhuoming, Livingston, Brandi, Logue, James P, Luo, Yang, McDermott, Adrian B, McElrath, Margaret J, Meliopoulos, Victoria A, Menachery, Vineet D, Montefiori, David C, Mühlemann, Barbara, Munster, Vincent J, Munt, Jenny E, Nair, Manoj S, Netzl, Antonia, Niewiadomska, Anna M, O’Dell, Sijy, Pekosz, Andrew, Perlman, Stanley, Pontelli, Marjorie C, Rockx, Barry, Rolland, Morgane, Rothlauf, Paul W, Sacharen, Sinai, Scheuermann, Richard H, Schmidt, Stephen D, Schotsaert, Michael, Schultz-Cherry, Stacey, Seder, Robert A, Sedova, Mayya, Sette, Alessandro, Shabman, Reed S, Shen, Xiaoying, Shi, Pei-Yong, Shukla, Maulik, Simon, Viviana, Stumpf, Spencer, Sullivan, Nancy J, Thackray, Larissa B, and Theiler, James

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Emerging Infectious Diseases, Pneumonia, Vaccine Related, Pneumonia & Influenza, Infectious Diseases, Biodefense, Immunization, Biotechnology, Prevention, Lung, Prevention of disease and conditions, and promotion of well-being, 2.1 Biological and endogenous factors, 3.4 Vaccines, Aetiology, Infection, Good Health and Well Being, Animals, Biological Evolution, COVID-19, COVID-19 Vaccines, Humans, National Institute of Allergy and Infectious Diseases (U.S.), Pandemics, Pharmacogenomic Variants, SARS-CoV-2, United States, Virulence, General Science & Technology
Abstract

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

Published
2022

8. Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking

Author

Liu, Lihong, Casner, Ryan G., Guo, Yicheng, Wang, Qian, Iketani, Sho, Chan, Jasper Fuk-Woo., Yu, Jian, Dadonaite, Bernadeta, Nair, Manoj S., Mohri, Hiroshi, Reddem, Eswar R., Yuan, Shuofeng, Poon, Vincent Kwok-Man, Chan, Chris Chung-Sing, Yuen, Kwok-Yung, Sheng, Zizhang, Huang, Yaoxing, Bloom, Jesse D., Shapiro, Lawrence, and Ho, David D.

Published
2023
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10. Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Author

King, Hannah A. D., Joyce, M. Gordon, Lakhal-Naouar, Ines, Ahmed, Aslaa, Cincotta, Camila Macedo, Subra, Caroline, Peachman, Kristina K., Hack, Holly R., Chen, Rita E., Thomas, Paul V., Chen, Wei-Hung, Sankhala, Rajeshwer S., Hajduczki, Agnes, Martinez, Elizabeth J., Peterson, Caroline E., Chang, William C., Choe, Misook, Smith, Clayton, Headley, Jarrett A., Elyard, Hanne A., Cook, Anthony, Anderson, Alexander, Wuertz, Kathryn McGuckin, Dong, Ming, Swafford, Isabella, Case, James B., Currier, Jeffrey R., Lal, Kerri G., Amare, Mihret F., Dussupt, Vincent, Molnar, Sebastian, Daye, Sharon P., Zeng, Xiankun, Barkei, Erica K., Alfson, Kendra, Staples, Hilary M., Carrion, Ricardo, Krebs, Shelly J., Paquin-Proulx, Dominic, Karasavvas, Nicos, Polonis, Victoria R., Jagodzinski, Linda L., Vasan, Sandhya, Scott, Paul T., Huang, Yaoxing, Nair, Manoj S., Ho, David D., de Val, Natalia, Diamond, Michael S., Lewisi, Mark G., Rao, Mangala, Matyas, Gary R., Gromowski, Gregory D., Peel, Sheila A., Michael, Nelson L., Modjarrad, Kayvon, and Bolton, Diane L.

Published
2021

12. Antibody evasion properties of SARS-CoV-2 Omicron sublineages

Author

Iketani, Sho, Liu, Lihong, Guo, Yicheng, Liu, Liyuan, Chan, Jasper F.-W., Huang, Yiming, Wang, Maple, Luo, Yang, Yu, Jian, Chu, Hin, Chik, Kenn K.-H., Yuen, Terrence T.-T., Yin, Michael T., Sobieszczyk, Magdalena E., Huang, Yaoxing, Yuen, Kwok-Yung, Wang, Harris H., Sheng, Zizhang, and Ho, David D.

Published
2022
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14. Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19

Author

Liu, Hengrui, Iketani, Sho, Zask, Arie, Khanizeman, Nisha, Bednarova, Eva, Forouhar, Farhad, Fowler, Brandon, Hong, Seo Jung, Mohri, Hiroshi, Nair, Manoj S., Huang, Yaoxing, Tay, Nicholas E. S., Lee, Sumin, Karan, Charles, Resnick, Samuel J., Quinn, Colette, Li, Wenjing, Shion, Henry, Xia, Xin, Daniels, Jacob D., Bartolo-Cruz, Michelle, Farina, Marcelo, Rajbhandari, Presha, Jurtschenko, Christopher, Lauber, Matthew A., McDonald, Thomas, Stokes, Michael E., Hurst, Brett L., Rovis, Tomislav, Chavez, Alejandro, Ho, David D., and Stockwell, Brent R.

Published
2022
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15. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2

Author

Liu, Lihong, Iketani, Sho, Guo, Yicheng, Chan, Jasper F.-W., Wang, Maple, Liu, Liyuan, Luo, Yang, Chu, Hin, Huang, Yiming, Nair, Manoj S., Yu, Jian, Chik, Kenn K.-H., Yuen, Terrence T.-T., Yoon, Chaemin, To, Kelvin K.-W., Chen, Honglin, Yin, Michael T., Sobieszczyk, Magdalena E., Huang, Yaoxing, Wang, Harris H., Sheng, Zizhang, Yuen, Kwok-Yung, and Ho, David D.

Published
2022
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16. Developing inhibitory peptides against SARS-CoV-2 envelope protein

Author

Bekdash, Ramsey, primary, Yoshida, Kazushige, additional, Nair, Manoj S., additional, Qiu, Lauren, additional, Ahdout, Johnathan, additional, Tsai, Hsiang-Yi, additional, Uryu, Kunihiro, additional, Soni, Rajesh K., additional, Huang, Yaoxing, additional, Ho, David D., additional, and Yazawa, Masayuki, additional

Published
2024
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17. Emergence and expansion of SARS-CoV-2 B.1.526 after identification in New York

Author

Annavajhala, Medini K., Mohri, Hiroshi, Wang, Pengfei, Nair, Manoj, Zucker, Jason E., Sheng, Zizhang, Gomez-Simmonds, Angela, Kelley, Anne L., Tagliavia, Maya, Huang, Yaoxing, Bedford, Trevor, Ho, David D., and Uhlemann, Anne-Catrin

Subjects
Company distribution practices, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution.sup.1-3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies.sup.4. Two signature spike mutations of concern are E484K, which has a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here we report the emergence of the variant lineage B.1.526 (also known as the Iota variant.sup.5), which contains E484K, and its rise to dominance in New York City in early 2021. This variant is partially or completely resistant to two therapeutic monoclonal antibodies that are in clinical use and is less susceptible to neutralization by plasma from individuals who had recovered from SARS-CoV-2 infection or serum from vaccinated individuals, posing a modest antigenic challenge. The presence of the B.1.526 lineage has now been reported in all 50 states in the United States and in many other countries. B.1.526 rapidly replaced earlier lineages in New York, with an estimated transmission advantage of 35%. These transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, are likely to have contributed to the sharp rise and rapid spread of B.1.526. Although SARS-CoV-2 B.1.526 initially outpaced B.1.1.7 in the region, its growth subsequently slowed concurrently with the rise of B.1.1.7 and ensuing variants. The dynamics of the spread of the SARS-CoV-2 variant B.1.526 suggest that resistance to neutralization by antibodies may evolve in other variants and contribute to the spread of COVID-19., Author(s): Medini K. Annavajhala [sup.1] , Hiroshi Mohri [sup.2] , Pengfei Wang [sup.2] , Manoj Nair [sup.2] , Jason E. Zucker [sup.1] , Zizhang Sheng [sup.2] , Angela Gomez-Simmonds [sup.1] [...]

Published
2021
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21. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants

Author

Xu, Jianliang, Xu, Kai, Jung, Seolkyoung, Conte, Andrea, Lieberman, Jenna, Muecksch, Frauke, Lorenzi, Julio Cesar Cetrulo, Park, Solji, Schmidt, Fabian, Wang, Zijun, Huang, Yaoxing, Luo, Yang, Nair, Manoj S., Wang, Pengfei, Schulz, Jonathan E., Tessarollo, Lino, Bylund, Tatsiana, Chuang, Gwo-Yu, Olia, Adam S., Stephens, Tyler, Teng, I-Ting, Tsybovsky, Yaroslav, Zhou, Tongqing, Munster, Vincent, Ho, David D., Hatziioannou, Theodora, Bieniasz, Paul D., Nussenzweig, Michel C., Kwong, Peter D., and Casellas, Rafael

Published
2021
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22. SARS-CoV-2 infection causes dopaminergic neuron senescence

Author

Yang, Liuliu, Kim, Tae Wan, Han, Yuling, Nair, Manoj S., Harschnitz, Oliver, Zhu, Jiajun, Wang, Pengfei, Koo, So Yeon, Lacko, Lauretta A., Chandar, Vasuretha, Bram, Yaron, Zhang, Tuo, Zhang, Wei, He, Feng, Pan, Chendong, Wu, Junjie, Huang, Yaoxing, Evans, Todd, van der Valk, Paul, Titulaer, Maarten J., Spoor, Jochem K.H., Furler O'Brien, Robert L., Bugiani, Marianna, D.J. Van de Berg, Wilma, Schwartz, Robert E., Ho, David D., Studer, Lorenz, Chen, Shuibing, Yang, Liuliu, Kim, Tae Wan, Han, Yuling, Nair, Manoj S., Harschnitz, Oliver, Zhu, Jiajun, Wang, Pengfei, Koo, So Yeon, Lacko, Lauretta A., Chandar, Vasuretha, Bram, Yaron, Zhang, Tuo, Zhang, Wei, He, Feng, Pan, Chendong, Wu, Junjie, Huang, Yaoxing, Evans, Todd, van der Valk, Paul, Titulaer, Maarten J., Spoor, Jochem K.H., Furler O'Brien, Robert L., Bugiani, Marianna, D.J. Van de Berg, Wilma, Schwartz, Robert E., Ho, David D., Studer, Lorenz, and Chen, Shuibing

Abstract

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Published
2024

23. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Author

Wang, Pengfei, Nair, Manoj S., Liu, Lihong, Iketani, Sho, Luo, Yang, Guo, Yicheng, Wang, Maple, Yu, Jian, Zhang, Baoshan, Kwong, Peter D., Graham, Barney S., Mascola, John R., Chang, Jennifer Y., Yin, Michael T., Sobieszczyk, Magdalena, Kyratsous, Christos A., Shapiro, Lawrence, Sheng, Zizhang, Huang, Yaoxing, and Ho, David D.

Published
2021
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25. SARS-CoV-2 infection causes dopaminergic neuron senescence

Author

Yang, Liuliu, primary, Kim, Tae Wan, additional, Han, Yuling, additional, Nair, Manoj S., additional, Harschnitz, Oliver, additional, Zhu, Jiajun, additional, Wang, Pengfei, additional, Koo, So Yeon, additional, Lacko, Lauretta A., additional, Chandar, Vasuretha, additional, Bram, Yaron, additional, Zhang, Tuo, additional, Zhang, Wei, additional, He, Feng, additional, Pan, Chendong, additional, Wu, Junjie, additional, Huang, Yaoxing, additional, Evans, Todd, additional, van der Valk, Paul, additional, Titulaer, Maarten J., additional, Spoor, Jochem K.H., additional, Furler O’Brien, Robert L., additional, Bugiani, Marianna, additional, D.J. Van de Berg, Wilma, additional, Schwartz, Robert E., additional, Ho, David D., additional, Studer, Lorenz, additional, and Chen, Shuibing, additional

Published
2024
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26. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Author

Han, Yuling, Duan, Xiaohua, Yang, Liuliu, Nilsson-Payant, Benjamin E., Wang, Pengfei, Duan, Fuyu, Tang, Xuming, Yaron, Tomer M., Zhang, Tuo, Uhl, Skyler, Bram, Yaron, Richardson, Chanel, Zhu, Jiajun, Zhao, Zeping, Redmond, David, Houghton, Sean, Nguyen, Duc-Huy T., Xu, Dong, Wang, Xing, Jessurun, Jose, Borczuk, Alain, Huang, Yaoxing, Johnson, Jared L., Liu, Yuru, Xiang, Jenny, Wang, Hui, Cantley, Lewis C., tenOever, Benjamin R., Ho, David D., Pan, Fong Cheng, Evans, Todd, Chen, Huanhuan Joyce, Schwartz, Robert E., and Chen, Shuibing

Published
2021
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30. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Author

Liu, Lihong, Wang, Pengfei, Nair, Manoj S., Yu, Jian, Rapp, Micah, Wang, Qian, Luo, Yang, Chan, Jasper F.-W., Sahi, Vincent, Figueroa, Amir, Guo, Xinzheng V., Cerutti, Gabriele, Bimela, Jude, Gorman, Jason, Zhou, Tongqing, Chen, Zhiwei, Yuen, Kwok-Yung, Kwong, Peter D., Sodroski, Joseph G., Yin, Michael T., Sheng, Zizhang, Huang, Yaoxing, Shapiro, Lawrence, and Ho, David D.

Published
2020
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31. Identification of Novel Susceptible Genes of Gastric Cancer Based on Integrated Omics Data

Author

Huang Yaoxing, Yu Danchun, Sun Xiaojuan, Jiang Shuman, Yan Qingqing, and Jia Lin

Subjects
gastric cancer, GWAS, integrated omics data, a machine learning based method, biomarkers, Biology (General), QH301-705.5
Abstract

Gastric cancer (GC) is one of the most common causes of cancer-related deaths in the world. This cancer has been regarded as a biological and genetically heterogeneous disease with a poorly understood carcinogenesis at the molecular level. Thousands of biomarkers and susceptible loci have been explored via experimental and computational methods, but their effects on disease outcome are still unknown. Genome-wide association studies (GWAS) have identified multiple susceptible loci for GC, but due to the linkage disequilibrium (LD), single-nucleotide polymorphisms (SNPs) may fall within the non-coding region and exert their biological function by modulating the gene expression level. In this study, we collected 1,091 cases and 410,350 controls from the GWAS catalog database. Integrating with gene expression level data obtained from stomach tissue, we conducted a machine learning-based method to predict GC-susceptible genes. As a result, we identified 787 novel susceptible genes related to GC, which will provide new insight into the genetic and biological basis for the mechanism and pathology of GC development.

Published
2021
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32. An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo

Author

Tsuji, Moriya, primary, Nair, Manoj S., additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand L., additional, Seehra, Kuljeet, additional, Hwang, Youngmin, additional, Ribeiro, Ágata Lopes, additional, Ferreira, Geovane Marques, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Grazziela Alves, additional, Tsuji, Yukiko, additional, Mori, Munemasa, additional, Boon, Adrianus C. M., additional, Diamond, Michael S., additional, Huang, Yaoxing, additional, and Ho, David D., additional

Published
2023
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34. A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

Author

Burn Aschner, Clare, primary, Muthuraman, Krithika, additional, Kucharska, Iga, additional, Cui, Hong, additional, Prieto, Katherine, additional, Nair, Manoj S., additional, Wang, Maple, additional, Huang, Yaoxing, additional, Christie-Holmes, Natasha, additional, Poon, Betty, additional, Lam, Jessica, additional, Sultana, Azmiri, additional, Kozak, Robert, additional, Mubareka, Samira, additional, Rubinstein, John L., additional, Rujas, Edurne, additional, Treanor, Bebhinn, additional, Ho, David D., additional, Jetha, Arif, additional, and Julien, Jean-Philippe, additional

Published
2023
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35. Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking

Author

Liu, Lihong, primary, Casner, Ryan G, additional, Guo, Yicheng, additional, Wang, Qian, additional, Iketani, Sho, additional, Chan, Jasper Fuk-Woo, additional, Yu, Jian, additional, Dadonaite, Bernadeta, additional, Nair, Manoj S, additional, Mohri, Hiroshi, additional, Reddem, Eswar R, additional, Yuan, Shuofeng, additional, Poon, Vincent Kwok-Man, additional, Chan, Chris Chung-Sing, additional, Yuen, Kwok-Yung, additional, Sheng, Zizhang, additional, Huang, Yaoxing, additional, Bloom, Jesse D, additional, Shapiro, Lawrence, additional, and Ho, David D, additional

Published
2023
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36. An Immunostimulatory Glycolipid That Blocks SARS-CoV-2, RSV, and Influenza Infections In Vivo

Author

Ho, David, primary, Tsuji, Moriya, additional, Nair, Manoj, additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand, additional, Seehra, Kuljeet, additional, Ribeiro, Ágata, additional, Ferreira, Geovane, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Alves, additional, Tsuji, Yukiko, additional, Boon, Adrianus, additional, Diamond, Michael, additional, Huang, Yaoxing, additional, Hwang, Youngmin, additional, and Mori, Munemasa, additional

Published
2023
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37. A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

Author

Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Ministry of Colleges and Universities (Ontario), Bill & Melinda Gates Foundation, Hospital for Sick Children (Canada), Ontario Graduate Scholarship, Canada Research Chairs, Canada Foundation for Innovation, Ontario Research Fund, National Cancer Institute (US), National Institute of General Medical Sciences (US), Department of Energy (US), Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, Julien, Jean-Philippe, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Ministry of Colleges and Universities (Ontario), Bill & Melinda Gates Foundation, Hospital for Sick Children (Canada), Ontario Graduate Scholarship, Canada Research Chairs, Canada Foundation for Innovation, Ontario Research Fund, National Cancer Institute (US), National Institute of General Medical Sciences (US), Department of Energy (US), Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, and Julien, Jean-Philippe

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.

Published
2023

38. Supplementary Materials for A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

Author

Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, Julien, Jean-Philippe, Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, and Julien, Jean-Philippe

Abstract

The PDF file includes: Supplementary Materials and Methods Figs. S1 to S10 Tables S1 to S3 Legend for data file S1 References (72–92) Other Supplementary Material for this manuscript includes the following: Data file S1 MDAR Reproducibility Checklist

Published
2023

39. Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study

Author

Hay, James A, primary, Kissler, Stephen M, primary, Fauver, Joseph R, primary, Mack, Christina, primary, Tai, Caroline G, additional, Samant, Radhika M, additional, Connolly, Sarah, additional, Anderson, Deverick J, additional, Khullar, Gaurav, additional, MacKay, Matthew, additional, Patel, Miral, additional, Kelly, Shannan, additional, Manhertz, April, additional, Eiter, Isaac, additional, Salgado, Daisy, additional, Baker, Tim, additional, Howard, Ben, additional, Dudley, Joel T, additional, Mason, Christopher E, additional, Nair, Manoj, additional, Huang, Yaoxing, additional, DiFiori, John, additional, Ho, David D, additional, Grubaugh, Nathan D, additional, and Grad, Yonatan H, additional

Published
2022
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41. Author response: Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study

Author

Hay, James A, primary, Kissler, Stephen M, primary, Fauver, Joseph R, primary, Mack, Christina, primary, Tai, Caroline G, additional, Samant, Radhika M, additional, Connolly, Sarah, additional, Anderson, Deverick J, additional, Khullar, Gaurav, additional, MacKay, Matthew, additional, Patel, Miral, additional, Kelly, Shannan, additional, Manhertz, April, additional, Eiter, Isaac, additional, Salgado, Daisy, additional, Baker, Tim, additional, Howard, Ben, additional, Dudley, Joel T, additional, Mason, Christopher E, additional, Nair, Manoj, additional, Huang, Yaoxing, additional, DiFiori, John, additional, Ho, David D, additional, Grubaugh, Nathan D, additional, and Grad, Yonatan H, additional

Published
2022
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42. Antibody avidity and multi-specificity combined to confer protection against SARS-CoV-2 and resilience against viral escape

Author

Aschner, Clare Burn, primary, Muthuraman, Krithika, additional, Kucharska, Iga, additional, Cui, Hong, additional, Prieto, Katherine, additional, Nair, Manoj S., additional, Wang, Maple, additional, Huang, Yaoxing, additional, Christie-Holmes, Natasha, additional, Poon, Betty, additional, Lam, Jessica, additional, Sultana, Azmiri, additional, Kozak, Robert, additional, Mubareka, Samira, additional, Rubinstein, John L., additional, Rujas, Edurne, additional, Treanor, Bebhinn, additional, Ho, David D., additional, Jetha, Arif, additional, and Julien, Jean-Philippe, additional

Published
2022
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45. An Immunostimulatory Glycolipid That Blocks SARS-CoV-2, RSV, and Influenza Infections In Vivo

Author

Ho, David, primary, Tsuji, Moriya, additional, Nair, Manoj, additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand, additional, Seehra, Kuljeet, additional, Ribeiro, Ágata, additional, Ferreira, Geovane, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Alves, additional, Tsuji, Yukiko, additional, Boon, Adrianus, additional, Diamond, Michael, additional, and Huang, Yaoxing, additional

Published
2022
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46. Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV ‐2

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Madan, Bharat, Reddem, Eswar R., Wang, Pengfei, Casner, Ryan G., Nair, Manoj S., Huang, Yaoxing, Fahad, Ahmed S., Souza, Matheus Oliveira, Banach, Bailey B., López Acevedo, Sheila N., Pan, Xiaoli, Nimrania, Rajani, Teng, I‐Ting, Bahna, Fabiana, Zhou, Tongqing, Zhang, Baoshan, Yin, Michael T., Ho, David D., Kwong, Peter D., Shapiro, Lawrence, DeKosky, Brandon J., Massachusetts Institute of Technology. Department of Chemical Engineering, Madan, Bharat, Reddem, Eswar R., Wang, Pengfei, Casner, Ryan G., Nair, Manoj S., Huang, Yaoxing, Fahad, Ahmed S., Souza, Matheus Oliveira, Banach, Bailey B., López Acevedo, Sheila N., Pan, Xiaoli, Nimrania, Rajani, Teng, I‐Ting, Bahna, Fabiana, Zhou, Tongqing, Zhang, Baoshan, Yin, Michael T., Ho, David D., Kwong, Peter D., Shapiro, Lawrence, and DeKosky, Brandon J.

Abstract

Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery.

Published
2022

47. Defining the risk of SARS-CoV-2 variants on immune protection

Author

DeGrace, Marciela M., Ghedin, Elodie, Frieman, Matthew B., Krammer, Florian, Grifoni, Alba, Alisoltani, Arghavan, Alter, Galit, Amara, Rama R., Baric, Ralph S., Barouch, Dan H., Bloom, Jesse D., Bloyet, Louis Marie, Bonenfant, Gaston, Boon, Adrianus C.M., Boritz, Eli A., Bratt, Debbie L., Bricker, Traci L., Brown, Liliana, Buchser, William J., Carreño, Juan Manuel, Cohen-Lavi, Liel, Darling, Tamarand L., Davis-Gardner, Meredith E., Dearlove, Bethany L., Di, Han, Dittmann, Meike, Doria-Rose, Nicole A., Douek, Daniel C., Drosten, Christian, Edara, Venkata Viswanadh, Ellebedy, Ali, Fabrizio, Thomas P., Ferrari, Guido, Fischer, Will M., Florence, William C., Fouchier, Ron A.M., Franks, John, García-Sastre, Adolfo, Godzik, Adam, Gonzalez-Reiche, Ana Silvia, Gordon, Aubree, Haagmans, Bart L., Halfmann, Peter J., Ho, David D., Holbrook, Michael R., Huang, Yaoxing, James, Sarah L., Jaroszewski, Lukasz, Jeevan, Trushar, Johnson, Robert M., Jones, Terry C., Joshi, Astha, Kawaoka, Yoshihiro, Kercher, Lisa, Koopmans, Marion P.G., Korber, Bette, Koren, Eilay, Koup, Richard A., LeGresley, Eric B., Lemieux, Jacob E., Liebeskind, Mariel J., Liu, Zhuoming, Livingston, Brandi, Logue, James P., Luo, Yang, McDermott, Adrian B., McElrath, Margaret J., Meliopoulos, Victoria A., Menachery, Vineet D., Montefiori, David C., Mühlemann, Barbara, Munster, Vincent J., Munt, Jenny E., Nair, Manoj S., Netzl, Antonia, Niewiadomska, Anna M., O’Dell, Sijy, Pekosz, Andrew, Perlman, Stanley, Pontelli, Marjorie C., Rockx, Barry, Rolland, Morgane, Rothlauf, Paul W., Sacharen, Sinai, Scheuermann, Richard H., Schmidt, Stephen D., Schotsaert, Michael, Schultz-Cherry, Stacey, Seder, Robert A., Sedova, Mayya, Sette, Alessandro, Shabman, Reed S., Shen, Xiaoying, Shi, Pei Yong, Shukla, Maulik, Simon, Viviana, Stumpf, Spencer, Sullivan, Nancy J., Thackray, Larissa B., Theiler, James, Thomas, Paul G., Trifkovic, Sanja, Türeli, Sina, Turner, Samuel A., Vakaki, Maria A., van Bakel, Harm, VanBlargan, Laura A., Vincent, Leah R., Wallace, Zachary S., Wang, Li, Wang, Maple, Wang, Pengfei, Wang, Wei, Weaver, Scott C., Webby, Richard J., Weiss, Carol D., Wentworth, David E., Weston, Stuart M., Whelan, Sean P.J., Whitener, Bradley M., Wilks, Samuel H., Xie, Xuping, Ying, Baoling, Yoon, Hyejin, Zhou, Bin, Hertz, Tomer, Smith, Derek J., Diamond, Michael S., Post, Diane J., Suthar, Mehul S., DeGrace, Marciela M., Ghedin, Elodie, Frieman, Matthew B., Krammer, Florian, Grifoni, Alba, Alisoltani, Arghavan, Alter, Galit, Amara, Rama R., Baric, Ralph S., Barouch, Dan H., Bloom, Jesse D., Bloyet, Louis Marie, Bonenfant, Gaston, Boon, Adrianus C.M., Boritz, Eli A., Bratt, Debbie L., Bricker, Traci L., Brown, Liliana, Buchser, William J., Carreño, Juan Manuel, Cohen-Lavi, Liel, Darling, Tamarand L., Davis-Gardner, Meredith E., Dearlove, Bethany L., Di, Han, Dittmann, Meike, Doria-Rose, Nicole A., Douek, Daniel C., Drosten, Christian, Edara, Venkata Viswanadh, Ellebedy, Ali, Fabrizio, Thomas P., Ferrari, Guido, Fischer, Will M., Florence, William C., Fouchier, Ron A.M., Franks, John, García-Sastre, Adolfo, Godzik, Adam, Gonzalez-Reiche, Ana Silvia, Gordon, Aubree, Haagmans, Bart L., Halfmann, Peter J., Ho, David D., Holbrook, Michael R., Huang, Yaoxing, James, Sarah L., Jaroszewski, Lukasz, Jeevan, Trushar, Johnson, Robert M., Jones, Terry C., Joshi, Astha, Kawaoka, Yoshihiro, Kercher, Lisa, Koopmans, Marion P.G., Korber, Bette, Koren, Eilay, Koup, Richard A., LeGresley, Eric B., Lemieux, Jacob E., Liebeskind, Mariel J., Liu, Zhuoming, Livingston, Brandi, Logue, James P., Luo, Yang, McDermott, Adrian B., McElrath, Margaret J., Meliopoulos, Victoria A., Menachery, Vineet D., Montefiori, David C., Mühlemann, Barbara, Munster, Vincent J., Munt, Jenny E., Nair, Manoj S., Netzl, Antonia, Niewiadomska, Anna M., O’Dell, Sijy, Pekosz, Andrew, Perlman, Stanley, Pontelli, Marjorie C., Rockx, Barry, Rolland, Morgane, Rothlauf, Paul W., Sacharen, Sinai, Scheuermann, Richard H., Schmidt, Stephen D., Schotsaert, Michael, Schultz-Cherry, Stacey, Seder, Robert A., Sedova, Mayya, Sette, Alessandro, Shabman, Reed S., Shen, Xiaoying, Shi, Pei Yong, Shukla, Maulik, Simon, Viviana, Stumpf, Spencer, Sullivan, Nancy J., Thackray, Larissa B., Theiler, James, Thomas, Paul G., Trifkovic, Sanja, Türeli, Sina, Turner, Samuel A., Vakaki, Maria A., van Bakel, Harm, VanBlargan, Laura A., Vincent, Leah R., Wallace, Zachary S., Wang, Li, Wang, Maple, Wang, Pengfei, Wang, Wei, Weaver, Scott C., Webby, Richard J., Weiss, Carol D., Wentworth, David E., Weston, Stuart M., Whelan, Sean P.J., Whitener, Bradley M., Wilks, Samuel H., Xie, Xuping, Ying, Baoling, Yoon, Hyejin, Zhou, Bin, Hertz, Tomer, Smith, Derek J., Diamond, Michael S., Post, Diane J., and Suthar, Mehul S.

Abstract

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

Published
2022

48. SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion

Author

Ho, David, primary, Wang, Qian, additional, Guo, Yicheng, additional, Iketani, Sho, additional, Li, Zhiteng, additional, Mohri, Hiroshi, additional, Wang, Maple, additional, Yu, Jian, additional, Bowen, Anthony, additional, Chang, Jennifer, additional, Shah, Jayesh, additional, Nguyen, Nadia, additional, Meyers, Kathrine, additional, Yin, Michael, additional, Sobieszczyk, Magdalena, additional, Sheng, Zizhang, additional, Huang, Yaoxing, additional, and Liu, Lihong, additional

Published
2022
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49. Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5

Author

Wang, Qian, primary, Guo, Yicheng, additional, Iketani, Sho, additional, Nair, Manoj S., additional, Li, Zhiteng, additional, Mohri, Hiroshi, additional, Wang, Maple, additional, Yu, Jian, additional, Bowen, Anthony D., additional, Chang, Jennifer Y., additional, Shah, Jayesh G., additional, Nguyen, Nadia, additional, Chen, Zhiwei, additional, Meyers, Kathrine, additional, Yin, Michael T., additional, Sobieszczyk, Magdalena E., additional, Sheng, Zizhang, additional, Huang, Yaoxing, additional, Liu, Lihong, additional, and Ho, David D., additional

Published
2022
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50. An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Author

Liu, Lihong, primary, Iketani, Sho, additional, Guo, Yicheng, additional, Reddem, Eswar R., additional, Casner, Ryan G., additional, Nair, Manoj S., additional, Yu, Jian, additional, Chan, Jasper F.-W., additional, Wang, Maple, additional, Cerutti, Gabriele, additional, Li, Zhiteng, additional, Morano, Nicholas C., additional, Castagna, Candace D., additional, Corredor, Laura, additional, Chu, Hin, additional, Yuan, Shuofeng, additional, Poon, Vincent Kwok-Man, additional, Chan, Chris Chun-Sing, additional, Chen, Zhiwei, additional, Luo, Yang, additional, Cunningham, Marcus, additional, Chavez, Alejandro, additional, Yin, Michael T., additional, Perlin, David S., additional, Tsuji, Moriya, additional, Yuen, Kwok-Yung, additional, Kwong, Peter D., additional, Sheng, Zizhang, additional, Huang, Yaoxing, additional, Shapiro, Lawrence, additional, and Ho, David D., additional

Published
2022
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