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1,877 results on '"Baric, Ralph S."'

1. A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants

Author

Liu, Xiang, Ng, Wern Hann, Zusinaite, Eva, Freitas, Joseph, Taylor, Adam, Yerragunta, Venugopal, Aavula, Shukra Madhaha, Gorriparthi, Sambaiah, Ponsekaran, Santhakumar, Bonda, Rama Lakshmi, Mani, Priyanka, Nimmagadda, Sridevi V., Wang, Sainan, Lello, Laura Sandra, Zaid, Ali, Dua, Ujjwal, Taft-Benz, Sharon A., Anderson, Elizabeth, Baxter, Victoria K., Sarkar, Sanjay, Ling, Zheng L., Ashhurst, Thomas M., Cheng, Samuel M. S., Pattnaik, Priyabrata, Kanakasapapathy, Anand Kumar, Baric, Ralph S., Burt, Felicity J., Peiris, Malik, Heise, Mark T., King, Nicholas J. C., Merits, Andres, Lingala, Rajendra, and Mahalingam, Suresh

Published
2024
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2. The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo

Author

Rhodin, Michael H. J., Reyes, Archie C., Balakrishnan, Anand, Bisht, Nalini, Kelly, Nicole M., Gibbons, Joyce Sweeney, Lloyd, Jonathan, Vaine, Michael, Cressey, Tessa, Crepeau, Miranda, Shen, Ruichao, Manalo, Nathan, Castillo, Jonathan, Levene, Rachel E., Leonard, Daniel, Zang, Tianzhu, Jiang, Lijuan, Daniels, Kellye, Cox, Robert M., Lieber, Carolin M., Wolf, Josef D., Plemper, Richard K., Leist, Sarah R., Scobey, Trevor, Baric, Ralph S., Wang, Guoqiang, Goodwin, Bryan, and Or, Yat Sun

Published
2024
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3. Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus

Author

Dillard, Jacob A., Taft-Benz, Sharon A., Knight, Audrey C., Anderson, Elizabeth J., Pressey, Katia D., Parotti, Breantié, Martinez, Sabian A., Diaz, Jennifer L., Sarkar, Sanjay, Madden, Emily A., De la Cruz, Gabriela, Adams, Lily E., Dinnon, III, Kenneth H., Leist, Sarah R., Martinez, David R., Schäfer, Alexandra, Powers, John M., Yount, Jr., Boyd L., Castillo, Izabella N., Morales, Noah L., Burdick, Jane, Evangelista, Mia Katrina D., Ralph, Lauren M., Pankow, Nicholas C., Linnertz, Colton L., Lakshmanane, Premkumar, Montgomery, Stephanie A., Ferris, Martin T., Baric, Ralph S., Baxter, Victoria K., and Heise, Mark T.

Published
2024
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4. A compendium of multi-omics data illuminating host responses to lethal human virus infections

Author

Eisfeld, Amie J., Anderson, Lindsey N., Fan, Shufang, Walters, Kevin B., Halfmann, Peter J., Westhoff Smith, Danielle, Thackray, Larissa B., Tan, Qing, Sims, Amy C., Menachery, Vineet D., Schäfer, Alexandra, Sheahan, Timothy P., Cockrell, Adam S., Stratton, Kelly G., Webb-Robertson, Bobbie-Jo M., Kyle, Jennifer E., Burnum-Johnson, Kristin E., Kim, Young-Mo, Nicora, Carrie D., Peralta, Zuleyma, N’jai, Alhaji U., Sahr, Foday, van Bakel, Harm, Diamond, Michael S., Baric, Ralph S., Metz, Thomas O., Smith, Richard D., Kawaoka, Yoshihiro, and Waters, Katrina M.

Published
2024
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6. Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice

Author

dos Santos Alves, Rúbens Prince, Timis, Julia, Miller, Robyn, Valentine, Kristen, Pinto, Paolla Beatriz Almeida, Gonzalez, Andrew, Regla-Nava, Jose Angel, Maule, Erin, Nguyen, Michael N., Shafee, Norazizah, Landeras-Bueno, Sara, Olmedillas, Eduardo, Laffey, Brett, Dobaczewska, Katarzyna, Mikulski, Zbigniew, McArdle, Sara, Leist, Sarah R., Kim, Kenneth, Baric, Ralph S., Ollmann Saphire, Erica, Elong Ngono, Annie, and Shresta, Sujan

Published
2024
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7. Emergence of Novel Norovirus GII.4 Variant

Author

Chhabra, Preeti, Tully, Damien C., Mans, Janet, Niendorf, Sandra, Barclay, Leslie, Cannon, Jennifer L., Montmayeur, Anna M., Pan, Chao-Yang, Page, Nicola, Williams, Rachel, Tutill, Helena, Roy, Sunando, Celma, Cristina, Beard, Stuart, Mallory, Michael L., Manouana, Gedeon Prince, Velavan, Thirumalaisamy P., Adegnika, Ayola Akim, Kremsner, Peter G., Lindesmith, Lisa C., Hue, Stephane, Baric, Ralph S., Breuer, Judith, and Vinje, Jan

Subjects
Medical research, Medicine, Experimental, Genomics, Gastroenteritis, Antigenic determinants, Amino acids, Viral proteins, Health
Abstract

Norovirus is the most common cause of acute gastroenteritis (AGE) worldwide. Norovirus has an [approximately equal to] 7.7 kb positive-sense single-stranded RNA genome organized into 3 open reading frames (ORFs). [...]

Published
2024
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8. 1‑O‑Octadecyl-2‑O‑benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV‑2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV‑2 Activity

Author

Carlin, Aaron F, Beadle, James R, Clark, Alex E, Gully, Kendra L, Moreira, Fernando R, Baric, Ralph S, Graham, Rachel L, Valiaeva, Nadejda, Leibel, Sandra L, Bray, William, McMillan, Rachel E, Freshman, Jonathan E, Garretson, Aaron F, McVicar, Rachael N, Rana, Tariq, Zhang, Xing-Quan, Murphy, Joyce A, Schooley, Robert T, and Hostetler, Karl Y

Subjects
Lung, Prevention, Emerging Infectious Diseases, Infectious Diseases, Infection, Animals, Mice, Antiviral Agents, SARS-CoV-2, COVID-19, Phospholipids, Medicinal and Biomolecular Chemistry, Organic Chemistry, Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry
Abstract

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

Published
2023

9. Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Author

Zhou, Panpan, Song, Ge, Liu, Hejun, Yuan, Meng, He, Wan-ting, Beutler, Nathan, Zhu, Xueyong, Tse, Longping V, Martinez, David R, Schäfer, Alexandra, Anzanello, Fabio, Yong, Peter, Peng, Linghang, Dueker, Katharina, Musharrafieh, Rami, Callaghan, Sean, Capozzola, Tazio, Limbo, Oliver, Parren, Mara, Garcia, Elijah, Rawlings, Stephen A, Smith, Davey M, Nemazee, David, Jardine, Joseph G, Safonova, Yana, Briney, Bryan, Rogers, Thomas F, Wilson, Ian A, Baric, Ralph S, Gralinski, Lisa E, Burton, Dennis R, and Andrabi, Raiees

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Biodefense, Prevention, Vaccine Related, Emerging Infectious Diseases, Biotechnology, Pneumonia, Pneumonia & Influenza, Lung, Immunization, Infection, Good Health and Well Being, Humans, SARS-CoV-2, Broadly Neutralizing Antibodies, COVID-19, Antibodies, Neutralizing, Antibodies, Viral, S2 stem-helix site, SARS-CoV-2 variants of concern, broad coronavirus protection, broadly neutralizing antibodies, coronavirus spike, coronaviruses, pan-betacoronavirus vaccines
Abstract

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

Published
2023

10. BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance

Author

Lee, Audrey, Floyd, Katharine, Wu, Shengyang, Fang, Zhuoqing, Tan, Tze Kai, Froggatt, Heather M., Powers, John M., Leist, Sarah R., Gully, Kendra L., Hubbard, Miranda L., Li, Chunfeng, Hui, Harold, Scoville, David, Ruggiero, Alistaire D., Liang, Yan, Pavenko, Anna, Lujan, Victor, Baric, Ralph S., Nolan, Garry P., Arunachalam, Prabhu S., Suthar, Mehul S., and Pulendran, Bali

Published
2024
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11. Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection

Author

Biering, Scott B, Sarnik, Sylvia A, Wang, Eleanor, Zengel, James R, Leist, Sarah R, Schäfer, Alexandra, Sathyan, Varun, Hawkins, Padraig, Okuda, Kenichi, Tau, Cyrus, Jangid, Aditya R, Duffy, Connor V, Wei, Jin, Gilmore, Rodney C, Alfajaro, Mia Madel, Strine, Madison S, Nguyenla, Xammy, Van Dis, Erik, Catamura, Carmelle, Yamashiro, Livia H, Belk, Julia A, Begeman, Adam, Stark, Jessica C, Shon, D Judy, Fox, Douglas M, Ezzatpour, Shahrzad, Huang, Emily, Olegario, Nico, Rustagi, Arjun, Volmer, Allison S, Livraghi-Butrico, Alessandra, Wehri, Eddie, Behringer, Richard R, Cheon, Dong-Joo, Schaletzky, Julia, Aguilar, Hector C, Puschnik, Andreas S, Button, Brian, Pinsky, Benjamin A, Blish, Catherine A, Baric, Ralph S, O’Neal, Wanda K, Bertozzi, Carolyn R, Wilen, Craig B, Boucher, Richard C, Carette, Jan E, Stanley, Sarah A, Harris, Eva, Konermann, Silvana, and Hsu, Patrick D

Subjects
Acute Respiratory Distress Syndrome, Clinical Research, Infectious Diseases, Pneumonia & Influenza, Rare Diseases, Biodefense, Lung, Vaccine Related, Pneumonia, Prevention, Emerging Infectious Diseases, Genetics, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Infection, Good Health and Well Being, Animals, COVID-19, Clustered Regularly Interspaced Short Palindromic Repeats, Epigenesis, Genetic, Humans, Mice, Mucins, SARS-CoV-2, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.

Published
2022

12. Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination

Author

Voss, William N., Mallory, Michael L., Byrne, Patrick O., Marchioni, Jeffrey M., Knudson, Sean A., Powers, John M., Leist, Sarah R., Dadonaite, Bernadeta, Townsend, Douglas R., Kain, Jessica, Huang, Yimin, Satterwhite, Ed, Castillo, Izabella N., Mattocks, Melissa, Paresi, Chelsea, Munt, Jennifer E., Scobey, Trevor, Seeger, Allison, Premkumar, Lakshmanane, Bloom, Jesse D., Georgiou, George, McLellan, Jason S., Baric, Ralph S., Lavinder, Jason J., and Ippolito, Gregory C.

Published
2024
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14. Host range, transmissibility and antigenicity of a pangolin coronavirus

Author

Hou, Yixuan J., Chiba, Shiho, Leist, Sarah R., Meganck, Rita M., Martinez, David R., Schäfer, Alexandra, Catanzaro, Nicholas J., Sontake, Vishwaraj, West, Ande, Edwards, Catlin E., Yount, Boyd, Lee, Rhianna E., Gallant, Samuel C., Zost, Seth J., Powers, John, Adams, Lily, Kong, Edgar F., Mattocks, Melissa, Tata, Aleksandra, Randell, Scott H., Tata, Purushothama R., Halfmann, Peter, Crowe, Jr, James E., Kawaoka, Yoshihiro, and Baric, Ralph S.

Published
2023
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15. Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Author

He, Wan-ting, Musharrafieh, Rami, Song, Ge, Dueker, Katharina, Tse, Longping V, Martinez, David R, Schäfer, Alexandra, Callaghan, Sean, Yong, Peter, Beutler, Nathan, Torres, Jonathan L, Volk, Reid M, Zhou, Panpan, Yuan, Meng, Liu, Hejun, Anzanello, Fabio, Capozzola, Tazio, Parren, Mara, Garcia, Elijah, Rawlings, Stephen A, Smith, Davey M, Wilson, Ian A, Safonova, Yana, Ward, Andrew B, Rogers, Thomas F, Baric, Ralph S, Gralinski, Lisa E, Burton, Dennis R, and Andrabi, Raiees

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related, Biodefense, Lung, Pneumonia & Influenza, Emerging Infectious Diseases, Infectious Diseases, Prevention, Pneumonia, Immunization, Biotechnology, Good Health and Well Being, Antibodies, Neutralizing, Antibodies, Viral, Broadly Neutralizing Antibodies, COVID-19, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Biochemistry and cell biology
Abstract

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.

Published
2022

16. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies

Author

Figueiredo, Jane C, Hirsch, Fred R, Kushi, Lawrence H, Nembhard, Wendy N, Crawford, James M, Mantis, Nicholas, Finster, Laurel, Merin, Noah M, Merchant, Akil, Reckamp, Karen L, Melmed, Gil Y, Braun, Jonathan, McGovern, Dermot, Parekh, Samir, Corley, Douglas A, Zohoori, Namvar, Amick, Benjamin C, Du, Ruofei, Gregersen, Peter K, Diamond, Betty, Taioli, Emanuela, Sariol, Carlos, Espino, Ana, Weiskopf, Daniela, Gifoni, Alba, Brien, James, Hanege, William, Lipsitch, Marc, Zidar, David A, McAlearney, Ann Scheck, Wajnberg, Ania, LaBaer, Joshua, Lewis, E Yvonne, Binder, Raquel A, Moormann, Ann M, Forconi, Catherine, Forrester, Sarah, Batista, Jennifer, Schieffelin, John, Kim, Dongjoo, Biancon, Giulia, VanOudenhove, Jennifer, Halene, Stephanie, Fan, Rong, Barouch, Dan H, Alter, Galit, Pinninti, Swetha, Boppana, Suresh B, Pati, Sunil K, Latting, Misty, Karaba, Andrew H, Roback, John, Sekaly, Rafick, Neish, Andrew, Brincks, Ahnalee M, Granger, Douglas A, Karger, Amy B, Thyagarajan, Bharat, Thomas, Stefani N, Klein, Sabra L, Cox, Andrea L, Lucas, Todd, Furr-Holden, Debra, Key, Kent, Jones, Nicole, Wrammerr, Jens, Suthar, Mehul, Wong, Serre Yu, Bowman, Natalie M, Simon, Viviana, Richardson, Lynne D, McBride, Russell, Krammer, Florian, Rana, Meenakshi, Kennedy, Joshua, Boehme, Karl, Forrest, Craig, Granger, Steve W, Heaney, Christopher D, Lapinski, Maria Knight, Wallet, Shannon, Baric, Ralph S, Schifanella, Luca, Lopez, Marcos, Fernández, Soledad, Kenah, Eben, Panchal, Ashish R, Britt, William J, Sanz, Iñaki, Dhodapkar, Madhav, Ahmed, Rafi, Bartelt, Luther A, Markmann, Alena J, Lin, Jessica T, Hagan, Robert S, Wolfgang, Matthew C, and Skarbinski, Jacek

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pneumonia & Influenza, Vaccine Related, Emerging Infectious Diseases, Biodefense, Lung, Digestive Diseases, Infectious Diseases, Clinical Research, Pneumonia, Cancer, Pediatric, Prevention, Aetiology, 2.4 Surveillance and distribution, Good Health and Well Being, cohort, COVID-19, epidemiology, SARS-CoV-2, serosurveillance, SeroNet, Clinical sciences, Medical microbiology
Abstract

BackgroundGlobal efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies.MethodsIn the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders).ResultsSeveral studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes.ConclusionsIn this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.

Published
2022

17. 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

18. mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies

Author

Montoya, Brian, Melo-Silva, Carolina R., Tang, Lingjuan, Kafle, Samita, Lidskiy, Peter, Bajusz, Csaba, Vadovics, Máté, Muramatsu, Hiromi, Abraham, Edit, Lipinszki, Zoltan, Chatterjee, Debotri, Scher, Gabrielle, Benitez, Juliana, Sung, Molly M.H., Tam, Ying K., Catanzaro, Nicholas J., Schäfer, Alexandra, Andino, Raul, Baric, Ralph S., Martinez, David R., Pardi, Norbert, and Sigal, Luis J.

Published
2024
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19. Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans

Author

Schäfer, Alexandra, Gralinski, Lisa E., Leist, Sarah R., Hampton, Brea K., Mooney, Michael A., Jensen, Kara L., Graham, Rachel L., Agnihothram, Sudhakar, Jeng, Sophia, Chamberlin, Steven, Bell, Timothy A., Scobey, D. Trevor, Linnertz, Colton L., VanBlargan, Laura A., Thackray, Larissa B., Hock, Pablo, Miller, Darla R., Shaw, Ginger D., Diamond, Michael S., de Villena, Fernando Pardo Manuel, McWeeney, Shannon K., Heise, Mark T., Menachery, Vineet D., Ferris, Martin T., and Baric, Ralph S.

Published
2024
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20. Mapping of susceptibility loci for Ebola virus pathogenesis in mice

Author

Schäfer, Alexandra, Marzi, Andrea, Furuyama, Wakako, Catanzaro, Nicholas J., Nguyen, Cameron, Haddock, Elaine, Feldmann, Friederike, Meade-White, Kimberly, Thomas, Tina, Hubbard, Miranda L., Gully, Kendra L., Leist, Sarah R., Hock, Pablo, Bell, Timothy A., De la Cruz, Gabriela E., Midkiff, Bentley R., Martinez, David R., Shaw, Ginger D., Miller, Darla R., Vernon, Michael J., Graham, Rachel L., Cowley, Dale O., Montgomery, Stephanie A., Schughart, Klaus, de Villena, Fernando Pardo Manuel, Wilkerson, Gregory K., Ferris, Martin T., Feldmann, Heinz, and Baric, Ralph S.

Published
2024
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21. Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera

Author

Hutchinson, Geoffrey B., Abiona, Olubukola M., Ziwawo, Cynthia T., Werner, Anne P., Ellis, Daniel, Tsybovsky, Yaroslav, Leist, Sarah R., Palandjian, Charis, West, Ande, Fritch, Ethan J., Wang, Nianshuang, Wrapp, Daniel, Boyoglu-Barnum, Seyhan, Ueda, George, Baker, David, Kanekiyo, Masaru, McLellan, Jason S., Baric, Ralph S., King, Neil P., Graham, Barney S., and Corbett-Helaire, Kizzmekia S.

Published
2023
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22. A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity

Author

Young, Ellen, Yount, Boyd, Pantoja, Petraleigh, Henein, Sandra, Meganck, Rita M., McBride, Jennifer, Munt, Jennifer E., Baric, Thomas J., Zhu, Deanna, Scobey, Trevor, Dong, Stephanie, Tse, Longping V., Martinez, Melween I., Burgos, Armando G., Graham, Rachel L., White, Laura, DeSilva, Aravinda, Sariol, Carlos A., and Baric, Ralph S.

Published
2023
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23. SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Author

Meganck, Rita M., Edwards, Caitlin E., Mallory, Michael L., Lee, Rhianna E., Dang, Hong, Bailey, Alexis B., Wykoff, Jason A., Gallant, Samuel C., Zhu, Deanna R., Yount, Boyd L., Kato, Takafumi, Shaffer, Kendall M., Nakano, Satoko, Cawley, Anne Marie, Sontake, Vishwaraj, Wang, Jeremy R., Hagan, Robert S., Miller, Melissa B., Tata, Purushothama Rao, Randell, Scott H., Tse, Longping V., Ehre, Camille, Okuda, Kenichi, Boucher, Richard C., and Baric, Ralph S.

Published
2024
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26. SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling

Author

Biering, Scott B, Gomes de Sousa, Francielle Tramontini, Tjang, Laurentia V, Pahmeier, Felix, Zhu, Chi, Ruan, Richard, Blanc, Sophie F, Patel, Trishna S, Worthington, Caroline M, Glasner, Dustin R, Castillo-Rojas, Bryan, Servellita, Venice, Lo, Nicholas TN, Wong, Marcus P, Warnes, Colin M, Sandoval, Daniel R, Clausen, Thomas Mandel, Santos, Yale A, Fox, Douglas M, Ortega, Victoria, Näär, Anders M, Baric, Ralph S, Stanley, Sarah A, Aguilar, Hector C, Esko, Jeffrey D, Chiu, Charles Y, Pak, John E, Beatty, P Robert, and Harris, Eva

Subjects
Biodefense, Lung, Infectious Diseases, Prevention, Vaccine Related, Pneumonia, Emerging Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, SARS-CoV-2, Angiotensin-Converting Enzyme 2, Spike Glycoprotein, Coronavirus, COVID-19, Endothelial Cells, Integrins, Peptidyl-Dipeptidase A, Transforming Growth Factor beta
Abstract

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Notably, we show that SARS-CoV-2 infection caused leak in vivo, which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered vascular leak, providing a starting point for development of therapies targeting COVID-19.

Published
2022

29. Hypergraph Models of Biological Networks to Identify Genes Critical to Pathogenic Viral Response

Author

Feng, Song, Heath, Emily, Jefferson, Brett, Joslyn, Cliff, Kvinge, Henry, Mitchell, Hugh D., Praggastis, Brenda, Eisfeld, Amie J., Sims, Amy C., Thackray, Larissa B., Fan, Shufang, Walters, Kevin B., Halfmann, Peter J., Westhoff-Smith, Danielle, Tan, Qing, Menachery, Vineet D., Sheahan, Timothy P., Cockrell, Adam S., Kocher, Jacob F., Stratton, Kelly G., Heller, Natalie C., Bramer, Lisa M., Diamond, Michael S., Baric, Ralph S., Waters, Katrina M., Kawaoka, Yoshihiro, McDermott, Jason E., and Purvine, Emilie

Subjects
Quantitative Biology - Quantitative Methods, Mathematics - Combinatorics, 92C42, 92-08, 05C65
Abstract

Background: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. Results: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. Conclusions: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.

Published
2020

30. Investigate the origins of COVID-19

Author

Bloom, Jesse D, Chan, Yujia Alina, Baric, Ralph S, Bjorkman, Pamela J, Cobey, Sarah, Deverman, Benjamin E, Fisman, David N, Gupta, Ravindra, Iwasaki, Akiko, Lipsitch, Marc, Medzhitov, Ruslan, Neher, Richard A, Nielsen, Rasmus, Patterson, Nick, Stearns, Tim, van Nimwegen, Erik, Worobey, Michael, and Relman, David A

Subjects
Animals, Biohazard Release, COVID-19, China, Humans, Pandemics, SARS-CoV-2, Viral Zoonoses, World Health Organization, General Science & Technology
Published
2021

31. Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination

Author

Munt, Jennifer E., Henein, Sandra, Adams, Cameron, Young, Ellen, Hou, Yixuan J., Conrad, Helen, Zhu, Deanna, Dong, Stephanie, Kose, Nurgun, Yount, Boyd, Meganck, Rita M., Tse, Long Ping V., Kuan, Guillermina, Balmaseda, Angel, Ricciardi, Michael J., Watkins, David I., Crowe, James E., Jr., Harris, Eva, DeSilva, Aravinda M., and Baric, Ralph S.

Published
2023
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32. Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice

Author

Martinez, David R., Schäfer, Alexandra, Gavitt, Tyler D., Mallory, Michael L., Lee, Esther, Catanzaro, Nicholas J., Chen, Haiyan, Gully, Kendra, Scobey, Trevor, Korategere, Pooja, Brown, Alecia, Smith, Lena, Parks, Robert, Barr, Maggie, Newman, Amanda, Bowman, Cindy, Powers, John M., Soderblom, Erik J., Mansouri, Katayoun, Edwards, Robert J., Baric, Ralph S., Haynes, Barton F., and Saunders, Kevin O.

Published
2023
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33. Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research

Author

Sigmon, John Sebastian, Blanchard, Matthew W, Baric, Ralph S, Bell, Timothy A, Brennan, Jennifer, Brockmann, Gudrun A, Burks, A Wesley, Calabrese, J Mauro, Caron, Kathleen M, Cheney, Richard E, Ciavatta, Dominic, Conlon, Frank, Darr, David B, Faber, James, Franklin, Craig, Gershon, Timothy R, Gralinski, Lisa, Gu, Bin, Gaines, Christiann H, Hagan, Robert S, Heimsath, Ernest G, Heise, Mark T, Hock, Pablo, Ideraabdullah, Folami, Jennette, J Charles, Kafri, Tal, Kashfeen, Anwica, Kulis, Mike, Kumar, Vivek, Linnertz, Colton, Livraghi-Butrico, Alessandra, Lloyd, KC Kent, Lutz, Cathleen, Lynch, Rachel M, Magnuson, Terry, Matsushima, Glenn K, McMullan, Rachel, Miller, Darla R, Mohlke, Karen L, Moy, Sheryl S, Murphy, Caroline EY, Najarian, Maya, O’Brien, Lori, Palmer, Abraham A, Philpot, Benjamin D, Randell, Scott H, Reinholdt, Laura, Ren, Yuyu, Rockwood, Steve, Rogala, Allison R, Saraswatula, Avani, Sassetti, Christopher M, Schisler, Jonathan C, Schoenrock, Sarah A, Shaw, Ginger D, Shorter, John R, Smith, Clare M, St. Pierre, Celine L, Tarantino, Lisa M, Threadgill, David W, Valdar, William, Vilen, Barbara J, Wardwell, Keegan, Whitmire, Jason K, Williams, Lucy, Zylka, Mark J, Ferris, Martin T, McMillan, Leonard, and de Villena, Fernando Pardo Manuel

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.6 Resources and infrastructure (aetiology), Animals, Female, Genome-Wide Association Study, Genotype, Genotyping Techniques, Male, Mice, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, Polymorphism, Genetic, Reproducibility of Results, Sex Determination Processes, genetic QC, genetic background, substrains, chromosomal sex, genetic constructs, diagnostic SNPs, Developmental Biology, Biochemistry and cell biology
Abstract

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research.

Published
2020

35. Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: A case study of bats.

Author

Olival, Kevin J, Cryan, Paul M, Amman, Brian R, Baric, Ralph S, Blehert, David S, Brook, Cara E, Calisher, Charles H, Castle, Kevin T, Coleman, Jeremy TH, Daszak, Peter, Epstein, Jonathan H, Field, Hume, Frick, Winifred F, Gilbert, Amy T, Hayman, David TS, Ip, Hon S, Karesh, William B, Johnson, Christine K, Kading, Rebekah C, Kingston, Tigga, Lorch, Jeffrey M, Mendenhall, Ian H, Peel, Alison J, Phelps, Kendra L, Plowright, Raina K, Reeder, DeeAnn M, Reichard, Jonathan D, Sleeman, Jonathan M, Streicker, Daniel G, Towner, Jonathan S, and Wang, Lin-Fa

Subjects
Animals, Animals, Wild, Chiroptera, Humans, Pneumonia, Viral, Coronavirus Infections, Genome, Viral, Host Specificity, Pandemics, Betacoronavirus, COVID-19, SARS-CoV-2, Wild, Genome, Viral, Pneumonia, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. The establishment of new wildlife reservoirs for SARS-CoV-2 would further complicate public health control measures and could lead to wildlife health and conservation impacts. Given the likely bat origin of SARS-CoV-2 and related beta-coronaviruses (β-CoVs), free-ranging bats are a key group of concern for spillover from humans back to wildlife. Here, we review the diversity and natural host range of β-CoVs in bats and examine the risk of humans inadvertently infecting free-ranging bats with SARS-CoV-2. Our review of the global distribution and host range of β-CoV evolutionary lineages suggests that 40+ species of temperate-zone North American bats could be immunologically naïve and susceptible to infection by SARS-CoV-2. We highlight an urgent need to proactively connect the wellbeing of human and wildlife health during the current pandemic and to implement new tools to continue wildlife research while avoiding potentially severe health and conservation impacts of SARS-CoV-2 "spilling back" into free-ranging bat populations.

Published
2020

36. Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies

Author

Young, Ellen, Carnahan, Robert H, Andrade, Daniela V, Kose, Nurgun, Nargi, Rachel S, Fritch, Ethan J, Munt, Jennifer E, Doyle, Michael P, White, Laura, Baric, Thomas J, Stoops, Mark, DeSilva, Aravinda, Tse, Longping V, Martinez, David R, Zhu, Deanna, Metz, Stefan, Wong, Marcus P, Espinosa, Diego A, Montoya, Magelda, Biering, Scott B, Sukulpolvi-Petty, Soila, Kuan, Guillermina, Balmaseda, Angel, Diamond, Michael S, Harris, Eva, Crowe, James E, and Baric, Ralph S

Subjects
Clinical Research, Immunization, Biotechnology, Biodefense, Infectious Diseases, Emerging Infectious Diseases, Prevention, Rare Diseases, Vector-Borne Diseases, Vaccine Related, Infection, Good Health and Well Being, Adolescent, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, B-Lymphocytes, Child, Child, Preschool, Chlorocebus aethiops, Dengue, Dengue Vaccines, Dengue Virus, Epitope Mapping, Epitopes, Humans, Mice, Models, Molecular, Nicaragua, Sequence Alignment, Serogroup, Vero Cells, Viral Envelope Proteins, Virion, DENV3, antigenic site, chimeric virus, dengue virus serotype 3, envelope protein, flavivirus, functional epitopes, in vivo protection, neutralizing monoclonal antibodies, Microbiology, Medical Microbiology, Immunology
Abstract

The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of Nicaragua and isolated 15 DENV3 TS mAbs recognizing the envelope (E) glycoprotein. Functional epitope mapping of these mAbs and small animal prophylaxis studies revealed a complex landscape with protective epitopes clustering in at least 6-7 antigenic sites. Potently neutralizing TS mAbs recognized sites principally in E glycoprotein domains I and II, and patterns suggest frequent recognition of quaternary structures on the surface of viral particles.

Published
2020

37. Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination

Author

Adams, Lily E., Leist, Sarah R., Dinnon, Kenneth H., III, West, Ande, Gully, Kendra L., Anderson, Elizabeth J., Loome, Jennifer F., Madden, Emily A., Powers, John M., Schäfer, Alexandra, Sarkar, Sanjay, Castillo, Izabella N., Maron, Jenny S., McNamara, Ryan P., Bertera, Harry L., Zweigart, Mark R., Higgins, Jaclyn S., Hampton, Brea K., Premkumar, Lakshmanane, Alter, Galit, Montgomery, Stephanie A., Baxter, Victoria K., Heise, Mark T., and Baric, Ralph S.

Published
2023
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39. Norovirus

Author

Lindesmith, Lisa C., primary, Verardi, Raffaello, additional, Mallory, Michael L., additional, Edwards, Caitlin E., additional, Graham, Rachel L., additional, Zweigart, Mark R., additional, Brewer-Jensen, Paul D., additional, Debbink, Kari, additional, Kocher, Jacob F., additional, Kwong, Peter D., additional, and Baric, Ralph S., additional

Published
2023
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40. Contributors

Author

Abzug, Mark J., primary, Acharya, Priyamvada, additional, Acosta, Anna M., additional, Ahmed, S. Sohail, additional, Amanna, Ian J., additional, Anderson, Annaliesa S., additional, Asturias, Edwin J., additional, Bachmann, Martin F., additional, Bahl, Sunil, additional, Bailey, Justin R., additional, Baker, Carol J., additional, Balfour, Henry H., additional, Baric, Ralph S., additional, Barnett, Elizabeth D., additional, Barrett, Alan D.T., additional, Belser, Jessica A., additional, Berzofsky, Jay A., additional, Bethony, Jeffrey M., additional, Brewer-Jensen, Paul D., additional, Bubak, Andrew N., additional, Burns, Cara C., additional, Caplan, Arthur L., additional, Cavaleri, Marco, additional, Chandran, Aruna, additional, Cherian, Thomas, additional, Clemens, John D., additional, Cochino, Emil, additional, Cohet, Catherine, additional, Cohn, Amanda, additional, Cortese, Margaret M., additional, Crowcroft, Natasha S., additional, Curtis, Nigel, additional, Damron, F. Heath, additional, Danchin, Margie, additional, Debbink, Kari, additional, Desai, Sachin N., additional, Davis, Emily H., additional, Decker, Michael D., additional, Denison, Mark R., additional, DeStefano, Frank, additional, Douglas, R. Gordon, additional, Dreher-Lesnick, Sheila M., additional, Eberhardt, Christiane S., additional, Edmunds, W. John, additional, Edwards, Caitlin E., additional, Edwards, Kathryn M., additional, Eggers, Rudolf, additional, Ellis, Ronald, additional, Erdman, Dean D., additional, Ertl, Hildegund C.J., additional, Estivariz, Concepcion F., additional, Fine, Paul E.M., additional, Finn, Theresa M., additional, Fisher, Allison M., additional, Fitzwater, Sean Patrick, additional, Freedman, Mark S., additional, Friede, Martin, additional, Friedlander, Arthur M., additional, Frumento, Nicole, additional, Fry, Alicia M., additional, Garçon, Nathalie, additional, Geris, Jennifer M., additional, Gershon, Anne A., additional, Gervier, Regis, additional, Gessner, Bradford D., additional, Gilbert, Peter B., additional, Gomez, Phillip Louis, additional, Ginsberg, Ann M., additional, Grabenstein, John D., additional, Graham, Rachel L., additional, Graham, Barney S., additional, Granoff, Dan M., additional, Gray, Gregory C., additional, Greenberg, David P., additional, Grohskopf, Lisa A., additional, Gruber, Marion F., additional, Guerena, Fernando B., additional, Havelange, Nicolas, additional, Halstead, Scott B., additional, Hanekom, Willem A., additional, Harrison, Lee H., additional, Hawn, Thomas R., additional, Haynes, Barton F., additional, Healy, C. Mary, additional, Hills, Susan L., additional, Hirabayashi, Kuniko, additional, Holmgren, Jan, additional, Hombach, Joachim M., additional, Hotez, Peter Jay, additional, Howe, Barbara J., additional, Hunegnaw, Ruth, additional, Izopet, Jacques, additional, Jamieson, Denise J., additional, Jansen, Kathrin, additional, Jarrahian, Courtney, additional, Johansen, Kari, additional, Kahn, Geoffrey D., additional, Karron, Ruth A., additional, Katz, Jacqueline M., additional, Kennedy, Richard B., additional, Broojerdi, Alireza Khadem, additional, Khetsuriani, Nino, additional, Khudyakov, Yury, additional, Klugman, Keith P., additional, Kocher, Jacob F., additional, Kollaritsch, Herwig, additional, Kotloff, Karen L., additional, Kozarsky, Phyllis E., additional, Kreimer, Aimée R., additional, Kroger, Andrew T., additional, Kwong, Peter D., additional, Lal, Manjari, additional, Levin, Myron J., additional, Levine, Myron M., additional, Lindesmith, Lisa C., additional, Lindstrand, Ann, additional, Ljungman, Per, additional, Lowy, Douglas R., additional, Lundgren, Anna, additional, Lydon, Patrick, additional, Macklin, Grace R., additional, Maeng, Hoyoung M., additional, Mahalingam, Ravi, additional, Malley, Richard, additional, Mallory, Michael L., additional, Marfin, Anthony A., additional, Markowitz, Lauri E., additional, Marshall, CDR Valerie, additional, McCollum, Andrea, additional, Meyer, Sarah, additional, McNamara, Lucy A., additional, Menning, Lisa, additional, Messacar, Kevin, additional, Miller, Mark A., additional, Milutinovic, Pavle, additional, Modlin, John F., additional, Monath, Thomas P., additional, Morabito, Kaitlyn M., additional, Moss, William J., additional, Mulholland, Kim, additional, Mura, Manuela, additional, Musher, Daniel M., additional, Nagel, Maria A., additional, Nair, G. Balakrish, additional, Nelson, Noele P., additional, Netea, Mihai G., additional, Neuzil, Kathleen Maletic, additional, Niemeyer, Christy S., additional, Nohynek, Hanna, additional, Norheim, Gunnstein, additional, Nussbaum, Lauren, additional, O’Brien, Katherine L., additional, O’Leary, Sean, additional, Ockenhouse, Christian, additional, Offit, Paul A., additional, Okwo-Bele, Jean-Marie, additional, Olkhanud, Purevdorj B., additional, Omer, Saad B., additional, Orenstein, Walter A., additional, Oyston, Petra C.F., additional, Parashar, Umesh D., additional, Patel, Manish M., additional, Payne, Daniel C., additional, Pebody, Richard, additional, Pecetta, Simone, additional, Perlman, Stanley, additional, Pierson, Benjamin, additional, Pierson, Theodore C., additional, Pittet, Laure F., additional, Pittman, Phillip R., additional, Plotkin, Stanley A., additional, Plotkin, Susan L., additional, Poland, Gregory A., additional, Pollard, Sir Andrew John, additional, Poovorawan, Yong, additional, Proctor, Richard A., additional, Qadri, Firdausi, additional, Rao, Agam, additional, Rappuoli, Rino, additional, Reef, Susan E., additional, Rogalewicz, Joseph A., additional, Robinson, James Michael, additional, Roesel, Sigrun, additional, Rubin, Steven A., additional, Rupprecht, Charles E., additional, Rutter, Paul, additional, Samant, Vijay B., additional, Sambhara, Suryaprakash, additional, Samies, Nicole L., additional, Santosham, Mathuram, additional, Saunders, Kevin O., additional, Schiller, John T., additional, Schleiss, Mark R., additional, Schuerman, Lode, additional, Schwab, Jennifer, additional, Schwartz, Jason L., additional, Scobie, Heather M., additional, Scott, J. Anthony, additional, Shapiro, Eugene D., additional, Shenoy, Erica S., additional, Shimabukuro, Tom T., additional, Shouval, Daniel, additional, Siegrist, Claire-Anne, additional, Sitrin, Robert D., additional, Skinner, Nicole E., additional, Slifka, Mark K., additional, Sodha, Samir V., additional, Soeters, Heidi M., additional, Solomon, Tom, additional, Speiser, Daniel E., additional, Staples, J. Erin, additional, Steffen, Robert, additional, Stephens, David S., additional, Strebel, Peter M., additional, Subbarao, Kanta, additional, Sullivan, Nancy J., additional, Takashima, Yoshihiro, additional, Tate, Jacqueline E., additional, Tayman, Alice, additional, Telford, Sam R., additional, Thombley, Melisa, additional, Thomsen, Isaac, additional, Tohme, Rania A., additional, Trabold, Malin, additional, El-Turabi, Aadil, additional, Vaughn, David W., additional, Verardi, Raffaello, additional, Vicari, Andrea S., additional, Vidor, Emmanuel J., additional, Villafana, Tonya, additional, Vogt, Matthew R., additional, Walker, Mark J., additional, Walsh, Nick M., additional, Wanlapakorn, Nasamon, additional, Ward, John W., additional, Wassilak, Steven G.F., additional, Watts, Lisa A., additional, Weber, David J., additional, Weiner, David B., additional, Weng, Mark K., additional, Wexler, Deborah L., additional, Wharton, Melinda, additional, Whitley, Richard J., additional, Whitney, Cynthia G., additional, Wiehe, Kevin, additional, Williamson, E. Diane, additional, Wormser, Gary P., additional, Xia, Ningshao, additional, Yildirim, Inci, additional, Zehrung, Darin, additional, and Zweigart, Mark R., additional

Published
2023
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42. COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort

Author

Mallory, Michael, primary, Munt, Jennifer E., additional, Narowski, Tara M., additional, Castillo, Izabella, additional, Cuadra, Edwing, additional, Pisanic, Nora, additional, Fields, Paul, additional, Powers, John M., additional, Dickson, Alexandria, additional, Harris, Rohan, additional, Wargowsky, Richard, additional, Moran, Seamus, additional, Allabban, Ahmed, additional, Raphel, Kristin, additional, McCaffrey, Timothy A., additional, Brien, James D., additional, Heaney, Christopher D., additional, Lafleur, John E., additional, Baric, Ralph S., additional, and Premkumar, Lakshmanane, additional

Published
2024
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43. The oral nucleoside prodrug GS-5245 is efficacious against SARS-CoV-2 and other endemic, epidemic, and enzootic coronaviruses

Author

Martinez, David R., primary, Moreira, Fernando R., additional, Catanzaro, Nicholas J., additional, Diefenbacher, Meghan V., additional, Zweigart, Mark R., additional, Gully, Kendra L., additional, De la Cruz, Gabriela, additional, Brown, Ariane J., additional, Adams, Lily E., additional, Yount, Boyd, additional, Baric, Thomas J., additional, Mallory, Michael L., additional, Conrad, Helen, additional, May, Samantha R., additional, Dong, Stephanie, additional, Scobey, D. Trevor, additional, Nguyen, Cameron, additional, Montgomery, Stephanie A., additional, Perry, Jason K., additional, Babusis, Darius, additional, Barrett, Kimberly T., additional, Nguyen, Anh-Hoa, additional, Nguyen, Anh-Quan, additional, Kalla, Rao, additional, Bannister, Roy, additional, Feng, Joy Y., additional, Cihlar, Tomas, additional, Baric, Ralph S., additional, Mackman, Richard L., additional, Bilello, John P., additional, Schäfer, Alexandra, additional, and Sheahan, Timothy P., additional

Published
2024
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45. Tracking the polyclonal neutralizing antibody response to a dengue virus serotype 1 type-specific epitope across two populations in Asia and the Americas

Author

Andrade, Daniela V, Warnes, Colin, Young, Ellen, Katzelnick, Leah C, Balmaseda, Angel, de Silva, Aravinda M, Baric, Ralph S, and Harris, Eva

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Emerging Infectious Diseases, Clinical Research, Prevention, Vector-Borne Diseases, Infectious Diseases, Vaccine Related, Biotechnology, Infection, Good Health and Well Being, Adolescent, Americas, Antibodies, Neutralizing, Antibodies, Viral, Asia, Child, Child, Preschool, Cross Reactions, Dengue, Dengue Virus, Epitopes, Female, Humans, Infant, Male, Models, Molecular, Protein Conformation, Serogroup
Abstract

The four dengue virus serotypes (DENV1-4) cause major public health problems worldwide. Highly neutralizing type-specific human monoclonal antibodies (hmAbs) target conformation-dependent epitopes on the DENV envelope protein, including 1F4, a DENV1 type-specific hmAb. Using a recombinant DENV2 virus displaying the DENV1 1F4 epitope (rDENV2/1), we measured the proportion and kinetics of DENV1 neutralizing antibodies targeting the 1F4 epitope in individuals living in Asia and the Americas where different DENV1 genotypes were circulating. Samples from 20 individuals were analyzed 3 and 18 months post-primary DENV1 infection, alongside samples from 4 individuals collected annually for four years post-primary DENV1 infection, from two studies in Nicaragua. We also analyzed convalescent post-primary DENV1 plasma samples from Sri Lankan individuals. We found that neutralizing antibodies recognizing the 1F4 epitope vary in prevalence across both populations and were detected from 20 days to four years post-infection. Additionally, both populations displayed substantial variability, with a range of high to low proportions of DENV1 type-specific neutralizing antibodies recognizing the 1F4 epitope seen across individuals. Thus, the 1F4 epitope is a major but not exclusive target of type-specific neutralizing antibodies post-primary infection with different DENV1 genotypes in Asia and Latin America, and additional epitopes likely contribute to type-specific neutralization of DENV1.

Published
2019

46. Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains

Author

Chen, Chuan, Saville, James W., Marti, Michelle M., Schäfer, Alexandra, Cheng, Mary Hongying, Mannar, Dhiraj, Zhu, Xing, Berezuk, Alison M., Banerjee, Anupam, Sobolewski, Michele D., Kim, Andrew, Treat, Benjamin R., Da Silva Castanha, Priscila Mayrelle, Enick, Nathan, McCormick, Kevin D., Liu, Xianglei, Adams, Cynthia, Hines, Margaret Grace, Sun, Zehua, Chen, Weizao, Jacobs, Jana L., Barratt-Boyes, Simon M., Mellors, John W., Baric, Ralph S., Bahar, Ivet, Dimitrov, Dimiter S., Subramaniam, Sriram, Martinez, David R., and Li, Wei

Published
2022
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47. Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Author

Li, Dapeng, Martinez, David R., Schäfer, Alexandra, Chen, Haiyan, Barr, Maggie, Sutherland, Laura L., Lee, Esther, Parks, Robert, Mielke, Dieter, Edwards, Whitney, Newman, Amanda, Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Gagne, Matthew, Douek, Daniel C., DeMarco, C. Todd, Denny, Thomas N., Oguin, III, Thomas H., Brown, Alecia, Rountree, Wes, Wang, Yunfei, Mansouri, Katayoun, Edwards, Robert J., Ferrari, Guido, Sempowski, Gregory D., Eaton, Amanda, Tang, Juanjie, Cain, Derek W., Santra, Sampa, Pardi, Norbert, Weissman, Drew, Tomai, Mark A., Fox, Christopher B., Moore, Ian N., Andersen, Hanne, Lewis, Mark G., Golding, Hana, Seder, Robert, Khurana, Surender, Baric, Ralph S., Montefiori, David C., Saunders, Kevin O., and Haynes, Barton F.

Published
2022
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49. IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern

Author

Chang, Matthew R., Tomasovic, Luke, Kuzmina, Natalia A., Ronk, Adam J., Byrne, Patrick O., Johnson, Rebecca, Storm, Nadia, Olmedillas, Eduardo, Hou, Yixuan J., Schäfer, Alexandra, Leist, Sarah R., Tse, Longping V., Ke, Hanzhong, Coherd, Christian, Nguyen, Katrina, Kamkaew, Maliwan, Honko, Anna, Zhu, Quan, Alter, Galit, Saphire, Erica Ollmann, McLellan, Jason S., Griffiths, Anthony, Baric, Ralph S., Bukreyev, Alexander, and Marasco, Wayne A.

Published
2022
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50. Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy

Author

Yamin, Rachel, Jones, Andrew T., Hoffmann, Hans-Heinrich, Schäfer, Alexandra, Kao, Kevin S., Francis, Rebecca L., Sheahan, Timothy P., Baric, Ralph S., Rice, Charles M., Ravetch, Jeffrey V., and Bournazos, Stylianos

Subjects
Mathematical optimization -- Usage, Monoclonal antibodies -- Usage -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease.sup.1-4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-19.sup.5. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-19.sup.6,7, we demonstrate that selective engagement of activating Fc[gamma] receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fc[gamma] receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fc[gamma] receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease. Optimization of monoclonal antibodies against SARS-CoV-2 for enhanced Fc-effector function increase their effectiveness for prevention and treatment of COVID-19 in multiple animal models of SARS-CoV-2 infection., Author(s): Rachel Yamin [sup.1] , Andrew T. Jones [sup.1] , Hans-Heinrich Hoffmann [sup.2] , Alexandra Schäfer [sup.3] , Kevin S. Kao [sup.1] , Rebecca L. Francis [sup.1] , Timothy P. [...]

Published
2021
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