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2. 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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3. Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus — Duke University, Durham, North Carolina, August 2–October 11, 2020

Author

Denny, Thomas N., Andrews, Laura, Bonsignori, Mattia, Cavanaugh, Kyle, Datto, Michael B., Deckard, Anastasia, DeMarco, C. Todd, DeNaeyer, Nicole, Epling, Carol A., Gurley, Thaddeus, Haase, Steven B., Hallberg, Chloe, Harer, John, Kneifel, Charles L., Lee, Mark J., Louzao, Raul, Moody, M. Anthony, Moore, Zack, Polage, Christopher R., Puglin, Jamie, Spotts, P. Hunter, Vaughn, John A., and Wolfe, Cameron R.

Published
2020

4. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Author

Saunders, Kevin O., Lee, Esther, Parks, Robert, Martinez, David R., Li, Dapeng, Chen, Haiyan, Edwards, Robert J., Gobeil, Sophie, Barr, Maggie, Mansouri, Katayoun, Alam, S. Munir, Sutherland, Laura L., Cai, Fangping, Sanzone, Aja M., Berry, Madison, Manne, Kartik, Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Kapingidza, Anyway B., Azoitei, Mihai, Tse, Longping V., Scobey, Trevor D., Spreng, Rachel L., Rountree, R. Wes, DeMarco, C. Todd, Denny, Thomas N., Woods, Christopher W., Petzold, Elizabeth W., Tang, Juanjie, Oguin, III, Thomas H., Sempowski, Gregory D., Gagne, Matthew, Douek, Daniel C., Tomai, Mark A., Fox, Christopher B., Seder, Robert, Wiehe, Kevin, Weissman, Drew, Pardi, Norbert, Golding, Hana, Khurana, Surender, Acharya, Priyamvada, Andersen, Hanne, Lewis, Mark G., Moore, Ian N., Montefiori, David C., Baric, Ralph S., and Haynes, Barton F.

Published
2021
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5. Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates

Author

Malewana, R. Dilshan, primary, Stalls, Victoria, additional, May, Aaron, additional, Lu, Xiaozhi, additional, Martinez, David R, additional, Schafer, Alexandra, additional, Li, Dapeng, additional, Barr, Maggie, additional, Sutherland, Laura L, additional, Lee, Esther, additional, Parks, Robert, additional, Beck, Whitney Edwards, additional, Newman, Amanda, additional, Bock, Kevin W, additional, Minai, Mahnaz, additional, Nagata, Bianca M, additional, DeMarco, C. Todd, additional, Denny, Thomas N, additional, Oguin, Thomas H, additional, Rountree, Wes, additional, Wang, Yunfei, additional, Mansouri, Katayoun, additional, Edwards, Robert J, additional, Sempowski, Gregory D, additional, Eaton, Amanda, additional, Muramatsu, Hiromi, additional, Henderson, Rory, additional, Tam, Ying, additional, Barbosa, Christopher, additional, Tang, Juanjie, additional, Cain, Derek W, additional, Santra, Sampa, additional, Moore, Ian N, additional, Andersen, Hanne, additional, Lewis, Mark G, additional, Golding, Hana, additional, Seder, Robert, additional, Khurana, Surender, additional, Montefiori, David C, additional, Pardi, Norbert, additional, Weissman, Drew, additional, Baric, Ralph S, additional, Acharya, Priyamvada, additional, Haynes, Barton F, additional, and Saunders, Kevin O, additional

Published
2023
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6. Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection

Author

Hurst, Jillian H, primary, Mohan, Aditya, additional, Dalapati, Trisha, additional, George, Ian A., additional, Aquino, Jhoanna N., additional, Lugo, Debra J., additional, Pfeiffer, Trevor S., additional, Rodriguez, Javier, additional, Rotta, Alexandre T., additional, Turner, Nicholas A., additional, Burke, Thomas W., additional, McClain, Micah T, additional, Henao, Ricardo, additional, DeMarco, C. Todd, additional, Louzao, Raul, additional, Denny, Thomas N., additional, Walsh, Kyle M., additional, Xu, Zhaohui, additional, Mejias, Asuncion, additional, Ramilo, Octavio, additional, Woods, Christopher W., additional, and Kelly, Matthew S, additional

Published
2023
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7. Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques

Author

Pahar, Bapi, primary, Gray, Wayne, additional, Fahlberg, Marissa, additional, Grasperge, Brooke, additional, Hunter, Meredith, additional, Das, Arpita, additional, Mabee, Christopher, additional, Aye, Pyone Pyone, additional, Schiro, Faith, additional, Hensley, Krystle, additional, Ratnayake, Aneeka, additional, Goff, Kelly, additional, LaBranche, Celia, additional, Shen, Xiaoying, additional, Tomaras, Georgia D., additional, DeMarco, C. Todd, additional, Montefiori, David, additional, Kissinger, Patricia, additional, Marx, Preston A., additional, and Traina-Dorge, Vicki, additional

Published
2022
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8. Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

Author

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

Published
2022
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9. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies

Author

Li, Dapeng, primary, Edwards, Robert J., additional, Manne, Kartik, additional, Martinez, David R., additional, Schäfer, Alexandra, additional, Alam, S. Munir, additional, Wiehe, Kevin, additional, Lu, Xiaozhi, additional, Parks, Robert, additional, Sutherland, Laura L., additional, Oguin, Thomas H., additional, McDanal, Charlene, additional, Perez, Lautaro G., additional, Mansouri, Katayoun, additional, Gobeil, Sophie M.C., additional, Janowska, Katarzyna, additional, Stalls, Victoria, additional, Kopp, Megan, additional, Cai, Fangping, additional, Lee, Esther, additional, Foulger, Andrew, additional, Hernandez, Giovanna E., additional, Sanzone, Aja, additional, Tilahun, Kedamawit, additional, Jiang, Chuancang, additional, Tse, Longping V., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Cronin, Kenneth, additional, Gee-Lai, Victoria, additional, Deyton, Margaret, additional, Barr, Maggie, additional, Von Holle, Tarra, additional, Macintyre, Andrew N., additional, Stover, Erica, additional, Feldman, Jared, additional, Hauser, Blake M., additional, Caradonna, Timothy M., additional, Scobey, Trevor D., additional, Rountree, Wes, additional, Wang, Yunfei, additional, Moody, M. Anthony, additional, Cain, Derek W., additional, DeMarco, C. Todd, additional, Denny, Thomas N., additional, Woods, Christopher W., additional, Petzold, Elizabeth W., additional, Schmidt, Aaron G., additional, Teng, I-Ting, additional, Zhou, Tongqing, additional, Kwong, Peter D., additional, Mascola, John R., additional, Graham, Barney S., additional, Moore, Ian N., additional, Seder, Robert, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Montefiori, David C., additional, Sempowski, Gregory D., additional, Baric, Ralph S., additional, Acharya, Priyamvada, additional, Haynes, Barton F., additional, and Saunders, Kevin O., additional

Published
2021
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10. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies

Author

Schäfer, Alexandra, Tilahun, Kedamawit, Seder, Robert, Li, Dapeng, Nagata, Bianca M., Feldman, Jared, Janowska, Katarzyna J., Baric, Ralph S., Manne, Kartik, Caradonna, Timothy M., Cronin, Kenneth, Denny, Thomas N., Moore, Ian N., Cain, Derek W., Zhou, Tongqing, Wang, Yunfei, Stover, Erica, Alam1, S. Munir, Minai, Mahnaz, Macintyre, Andrew N., Schmidt, Aaron G., Scobey, Trevor D., Bock, Kevin W., Tse, Longping V., Deyton, Margaret, Moody, M. Anthony, Barr, Maggie, Von Holle, Tarra, Perez, Lautaro G., Lee, Esther, Sutherland, Laura L., Montefiori, David C., Edwards, Robert J., Saunders, Kevin O., McDanal, Charlene, Hernandez, Giovanna E., Mansouri, Katayoun, Parks, Robert, Lu, Xiaozhi, Hauser, Blake M., DeMarco, C. Todd, Cai, Fangping, Graham, Barney S., Wiehe, Kevin, Mascola, John R., Sempowski, Gregory D., Andersen, Hanne, Petzold, Elizabeth W., Martinez, David R., Kwong, Peter D., Gee-Lai, Victoria, Kopp, Megan, Gobeil, Sophie M. C., Stalls, Victoria, Sanzone, Aja, Rountree, Wes, Haynes, Barton F., Lewis, Mark G., Acharya1, Priyamvada, Oguin III, Thomas H., Jiang, Chuancang, Teng, I-Ting, Foulger, Andrew, and Woods, Christopher W.

Subjects
viruses, fungi, respiratory system, skin and connective tissue diseases, respiratory tract diseases
Abstract

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-g (FcgR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcgR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

Published
2021
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11. SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

Author

Saunders, Kevin O., primary, Lee, Esther, additional, Parks, Robert, additional, Martinez, David R., additional, Li, Dapeng, additional, Chen, Haiyan, additional, Edwards, Robert J., additional, Gobeil, Sophie, additional, Barr, Maggie, additional, Mansouri, Katayoun, additional, Alam, S. Munir, additional, Sutherland, Laura L., additional, Cai, Fangping, additional, Sanzone, Aja M., additional, Berry, Madison, additional, Manne, Kartik, additional, Kapingidza, Anyway B., additional, Azoitei, Mihai, additional, Tse, Longping V., additional, Scobey, Trevor D., additional, Spreng, Rachel L., additional, Rountree, R. Wes, additional, DeMarco, C. Todd, additional, Denny, Thomas N., additional, Woods, Christopher W., additional, Petzold, Elizabeth W., additional, Oguin, Thomas H., additional, Sempowski, Gregory D., additional, Gagne, Matthew, additional, Douek, Daniel C., additional, Tomai, Mark A., additional, Fox, Christopher B., additional, Seder, Robert, additional, Wiehe, Kevin, additional, Weissman, Drew, additional, Pardi, Norbert, additional, Acharya, Priyamvada, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Moore, Ian N., additional, Montefiori, David C., additional, Baric, Ralph S., additional, and Haynes, Barton F., additional

Published
2021
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12. The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates

Author

Li, Dapeng, primary, Edwards, Robert J, additional, Manne, Kartik, additional, Martinez, David R., additional, Schäfer, Alexandra, additional, Alam, S. Munir, additional, Wiehe, Kevin, additional, Lu, Xiaozhi, additional, Parks, Robert, additional, Sutherland, Laura L., additional, Oguin, Thomas H., additional, McDanal, Charlene, additional, Perez, Lautaro G., additional, Mansouri, Katayoun, additional, Gobeil, Sophie M. C., additional, Janowska, Katarzyna, additional, Stalls, Victoria, additional, Kopp, Megan, additional, Cai, Fangping, additional, Lee, Esther, additional, Foulger, Andrew, additional, Hernandez, Giovanna E., additional, Sanzone, Aja, additional, Tilahun, Kedamawit, additional, Jiang, Chuancang, additional, Tse, Longping V., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Cronin, Kenneth, additional, Gee-Lai, Victoria, additional, Deyton, Margaret, additional, Barr, Maggie, additional, Holle, Tarra Von, additional, Macintyre, Andrew N., additional, Stover, Erica, additional, Feldman, Jared, additional, Hauser, Blake M., additional, Caradonna, Timothy M., additional, Scobey, Trevor D., additional, Rountree, Wes, additional, Wang, Yunfei, additional, Moody, M. Anthony, additional, Cain, Derek W., additional, DeMarco, C. Todd, additional, Denny, ThomasN., additional, Woods, Christopher W., additional, Petzold, Elizabeth W., additional, Schmidt, Aaron G., additional, Teng, I-Ting, additional, Zhou, Tongqing, additional, Kwong, Peter D., additional, Mascola, John R., additional, Graham, Barney S., additional, Moore, Ian N., additional, Seder, Robert, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Montefiori, David C., additional, Sempowski, Gregory D., additional, Baric, Ralph S., additional, Acharya, Priyamvada, additional, Haynes, Barton F., additional, and Saunders, Kevin O., additional

Published
2021
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13. Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study

Author

Hurst, Jillian H, primary, Heston, Sarah M, additional, Chambers, Hailey N, additional, Cunningham, Hannah M, additional, Price, Meghan J, additional, Suarez, Lilianna, additional, Crew, Carter G, additional, Bose, Shree, additional, Aquino, Jhoanna N, additional, Carr, Stuart T, additional, Griffin, S Michelle, additional, Smith, Stephanie H, additional, Jenkins, Kirsten, additional, Pfeiffer, Trevor S, additional, Rodriguez, Javier, additional, DeMarco, C Todd, additional, De Naeyer, Nicole A, additional, Gurley, Thaddeus C, additional, Louzao, Raul, additional, Zhao, Congwen, additional, Cunningham, Coleen K, additional, Steinbach, William J, additional, Denny, Thomas N, additional, Lugo, Debra J, additional, Moody, M Anthony, additional, Permar, Sallie R, additional, Rotta, Alexandre T, additional, Turner, Nicholas A, additional, Walter, Emmanuel B, additional, Woods, Christopher W, additional, and Kelly, Matthew S, additional

Published
2020
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14. SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study

Author

Hurst, Jillian H., primary, Heston, Sarah M., additional, Chambers, Hailey N., additional, Cunningham, Hannah M., additional, Price, Meghan J., additional, Suarez, Liliana, additional, Crew, Carter G., additional, Bose, Shree, additional, Aquino, Jhoanna N., additional, Carr, Stuart T., additional, Griffin, S. Michelle, additional, Smith, Stephanie H., additional, Jenkins, Kirsten, additional, Pfeiffer, Trevor S., additional, Rodriguez, Javier, additional, DeMarco, C. Todd, additional, De Naeyer, Nicole A., additional, Gurley, Thaddeus C., additional, Louzao, Raul, additional, Cunningham, Coleen K., additional, Steinbach, William J., additional, Denny, Thomas N., additional, Lugo, Debra J., additional, Moody, M. Anthony, additional, Permar, Sallie R., additional, Rotta, Alexandre T., additional, Turner, Nicholas A., additional, Walter, Emmanuel B., additional, Woods, Christopher W., additional, and Kelly, Matthew S., additional

Published
2020
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15. Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

Author

Hurst, Jillian H, Heston, Sarah M, Chambers, Hailey N, Cunningham, Hannah M, Price, Meghan J, Suarez, Lilianna, Crew, Carter G, Bose, Shree, Aquino, Jhoanna N, Carr, Stuart T, Griffin, S Michelle, Smith, Stephanie H, Jenkins, Kirsten, Pfeiffer, Trevor S, Rodriguez, Javier, DeMarco, C Todd, Naeyer, Nicole A De, Gurley, Thaddeus C, Louzao, Raul, and Zhao, Congwen

Subjects
COVID-19, BIOLOGICAL products
Abstract

Background Child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of SARS-CoV-2-related illnesses that the viruses causes in children. Methods We conducted a prospective cohort study of children and adolescents (aged <21 years) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time polymerase chain reaction assay. Results Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (P <.0001), less likely to have asthma (P =.005), and more likely to have an infected sibling contact (P =.001) than uninfected children. Children aged 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs 48%; P =.01) or adolescents (29% vs 60%; P <.001). Compared with children aged 6-13 years, adolescents more frequently reported influenza-like (61% vs 39%; P <.001) , and gastrointestinal (27% vs 9%; P =.002), and sensory symptoms (42% vs 9%; P <.0001) and had more prolonged illnesses (median [interquartile range] duration: 7 [4-12] vs 4 [3-8] days; P = 0.01). Despite the age-related variability in symptoms, wWe found no difference in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. Conclusions Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for coronavirus disease 2019 and in developing screening strategies for schools and childcare settings. [ABSTRACT FROM AUTHOR]

Published
2021
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16. Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Vectors Prime for Strong Cellular Responses to Simian Immunodeficiency Virus Gag in Rhesus Macaques

Author

Sixsmith, Jaimie D., primary, Panas, Michael W., additional, Lee, Sunhee, additional, Gillard, Geoffrey O., additional, White, KeriAnn, additional, Lifton, Michelle A., additional, Balachandran, Harikrishnan, additional, Mach, Linh, additional, Miller, John P., additional, Lavine, Christy, additional, DeMarco, C. Todd, additional, Tomaras, Georgia D., additional, Gee, Connie, additional, Porcelli, Steven A., additional, Larsen, Michelle H., additional, Frothingham, Richard, additional, Schmitz, Joern E., additional, Jacobs, William R., additional, Haynes, Barton F., additional, Letvin, Norman L., additional, and Korioth-Schmitz, Birgit, additional

Published
2014
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17. Development of a contemporary globally diverse HIV viral panel by the EQAPOL program

Author

Sanchez, Ana M., primary, DeMarco, C. Todd, additional, Hora, Bhavna, additional, Keinonen, Sarah, additional, Chen, Yue, additional, Brinkley, Christie, additional, Stone, Mars, additional, Tobler, Leslie, additional, Keating, Sheila, additional, Schito, Marco, additional, Busch, Michael P., additional, Gao, Feng, additional, and Denny, Thomas N., additional

Published
2014
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18. Transient Compartmentalization of Simian Immunodeficiency Virus Variants in the Breast Milk of African Green Monkeys

Author

Ho, Carrie, primary, Wu, Steven, additional, Amos, Joshua D., additional, Colvin, Lisa, additional, Smith, Shannon D., additional, Wilks, Andrew B., additional, DeMarco, C. Todd, additional, Brinkley, Christie, additional, Denny, Thomas N., additional, Schmitz, Joern E., additional, Rodrigo, Allen G., additional, and Permar, Sallie R., additional

Published
2013
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19. Lack of B Cell Dysfunction Is Associated with Functional, gp120-Dominant Antibody Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys

Author

Amos, Joshua D., primary, Wilks, Andrew B., additional, Fouda, Genevieve G., additional, Smith, Shannon D., additional, Colvin, Lisa, additional, Mahlokozera, Tatenda, additional, Ho, Carrie, additional, Beck, Krista, additional, Overman, R. Glenn, additional, DeMarco, C. Todd, additional, Hodge, Terry L., additional, LaBranche, Celia C., additional, Montefiori, David C., additional, Denny, Thomas N., additional, Liao, Hua-Xin, additional, Tomaras, Georgia D., additional, Moody, M. Anthony, additional, and Permar, Sallie R., additional

Published
2013
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20. Identification of anti-inflammatory targets for Huntington's disease using a brain slice-based screening assay

Author

Reinhart, Peter H., primary, Kaltenbach, Linda S., additional, Essrich, Christian, additional, Dunn, Denise E., additional, Eudailey, Joshua A., additional, DeMarco, C. Todd, additional, Turmel, Gregory J., additional, Whaley, Jennifer C., additional, Wood, Andrew, additional, Cho, Seongeun, additional, and Lo, Donald C., additional

Published
2011
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24. Recombinant Mycobacterium bovisBacillus Calmette-Guérin Vectors Prime for Strong Cellular Responses to Simian Immunodeficiency Virus Gag in Rhesus Macaques

Author

Sixsmith, Jaimie D., Panas, Michael W., Lee, Sunhee, Gillard, Geoffrey O., White, KeriAnn, Lifton, Michelle A., Balachandran, Harikrishnan, Mach, Linh, Miller, John P., Lavine, Christy, DeMarco, C. Todd, Tomaras, Georgia D., Gee, Connie, Porcelli, Steven A., Larsen, Michelle H., Frothingham, Richard, Schmitz, Joern E., Jacobs, William R., Haynes, Barton F., Letvin, Norman L., and Korioth-Schmitz, Birgit

Abstract

ABSTRACTLive attenuated nonpathogenic Mycobacterium bovisbacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gagexpression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in an in vitroscreen for augmented immunogenicity. We demonstrated that BCG-SIVgagis able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.

Published
2014
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25. Selective inhibitors of death in mutant huntingtin cells.

Author

Varma, Hemant, Voisine, Cindy, DeMarco, C. Todd, Cattaneo, Elena, Lo, Donald C., Hart, Anne C., and Stockwell, Brent R.

Subjects
HUNTINGTON disease, NEURODEGENERATION, PATHOLOGICAL physiology, CELL culture, CELL death
Abstract

Huntington disease (HD) is an inherited neurodegenerative disorder with unclear pathophysiology. We developed a high-throughput assay in a neuronal cell culture model of HD, screened 43,685 compounds and identified 29 novel selective inhibitors of cell death in mutant huntingtin–expressing cells. Four compounds were active in diverse HD models, which suggests a role for cell death in HD; these compounds are mechanistic probes and potential drug leads for HD. [ABSTRACT FROM AUTHOR]

Published
2007
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26. Selective Uncoupling of Gα12 from Rho-mediated Signaling.

Author

Meigs, Thomas E., Juneja, Juhi, DeMarco, C. Todd, Stemmle, Laura N., Kaplan, Daniel D., and Casey, Patrick J.

Subjects
*RHO GTPases, *GENETIC mutation, *GENETIC transcription, *G proteins, *GENETIC code, *GUANOSINE triphosphatase
Abstract

The heterotrimeric G protein G12 has been implicated in such cellular regulatory processes as cytoskeletal rearrangement, cell-cell adhesion, and oncogenic transformation. Although the activated α-subunit of G12 has been shown to interact directly with a number of protein effectors, the roles of many of these protein-protein interactions in G12-mediated cell physiology are poorly understood. To begin dissecting the specific cellular pathways engaged upon G12 activation, we produced a series of substitution mutants in the regions of Gα12 predicted to play a role in effector binding. Here we report the identification and characterization of an altered form of Gα12 that is functionally uncoupled from signaling through the monomeric G protein Rho, a protein known to propagate several Gα12-mediated signals. This mutant of Gα12 fails to bind the Rho-specific guanine nucleotide exchange factors pll5RhoGEF and LARG (leukemia-associated RhoGEF), fails to stimulate Rho-dependent transcriptional activation, and fails to trigger activation of RhoA and the Rho-mediated cellular responses of cell rounding and c-jun N-terminal kinase activation. Importantly, this mutant of Gα12 retains coupling to the effector protein E-cadherin, as evidenced by its ability both to bind E-cadherin in vitro and to disrupt E-cadherin-mediated cell-cell adhesion. Furthermore, this mutant retains the ability to trigger β-catenin release from the cytoplasmic domain of cadherin. This identification of a variant of Gα12 that is selectively uncoupled from one signaling pathway while retaining signaling capacity through a separate pathway will facilitate investigations into the mechanisms through which G12 proteins mediate diverse biological responses. [ABSTRACT FROM AUTHOR]

Published
2005
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27. Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

Author

Malewana RD, Stalls V, May A, Lu X, Martinez DR, Schäfer A, Li D, Barr M, Sutherland LL, Lee E, Parks R, Beck WE, Newman A, Bock KW, Minai M, Nagata BM, DeMarco CT, Denny TN, Oguin TH 3rd, Rountree W, Wang Y, Mansouri K, Edwards RJ, Sempowski GD, Eaton A, Muramatsu H, Henderson R, Tam Y, Barbosa C, Tang J, Cain DW, Santra S, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Montefiori DC, Pardi N, Weissman D, Baric RS, Acharya P, Haynes BF, and Saunders KO

Abstract

Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOCs including Omicron XBB.1.5, but lacked cross-Sarbecovirus neutralization. Structural analysis showed that the macaque broad SARS-CoV-2 VOC nAbs bound to the same epitope as a human broad SARS-CoV-2 VOC nAb, DH1193. Vaccine-induced antibodies that targeted the RBD inner face neutralized multiple Sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike lacking proline substitutions encoded by nucleoside-modified mRNA can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human Sarbecoviruses or recent Omicron VOCs., Competing Interests: Competing interests: DW and NP are inventors on patents regarding nucleoside modified mRNA. Ying Tam and Christopher Barbosa are employees of Acuitas Therapeutics. Rory Henderson has patents regarding engineered forms of Spike proteins. Barton Haynes, Kevin Saunders, Dapeng Li, Priyamvada Acharya, and Xiaozhi Lu have patents regarding human antibodies and their uses. N.P. served on the mRNA strategic advisory board of Sanofi Pasteur in 2022. N.P. is a member of the Scientific Advisory Board of AldexChem.

Published
2023
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28. Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Author

Hurst JH, Mohan AA, Dalapati T, George IA, Aquino JN, Lugo DJ, Pfeiffer TS, Rodriguez J, Rotta AT, Turner NA, Burke TW, McClain MT, Henao R, DeMarco CT, Louzao R, Denny TN, Walsh KM, Xu Z, Mejias A, Ramilo O, Woods CW, and Kelly MS

Abstract

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age., One Sentence Summary: Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.

Published
2023
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29. Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.

Author

Li D, Martinez DR, Schäfer A, Chen H, Barr M, Sutherland LL, Lee E, Parks R, Mielke D, Edwards W, Newman A, Bock KW, Minai M, Nagata BM, Gagne M, Douek DC, DeMarco CT, Denny TN, Oguin TH 3rd, Brown A, Rountree W, Wang Y, Mansouri K, Edwards RJ, Ferrari G, Sempowski GD, Eaton A, Tang J, Cain DW, Santra S, Pardi N, Weissman D, Tomai MA, Fox CB, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Baric RS, Montefiori DC, Saunders KO, and Haynes BF

Abstract

Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.

Published
2022
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30. The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

Author

Li D, Edwards RJ, Manne K, Martinez DR, Schäfer A, Alam SM, Wiehe K, Lu X, Parks R, Sutherland LL, Oguin TH, McDanal C, Perez LG, Mansouri K, Gobeil SMC, Janowska K, Stalls V, Kopp M, Cai F, Lee E, Foulger A, Hernandez GE, Sanzone A, Tilahun K, Jiang C, Tse LV, Bock KW, Minai M, Nagata BM, Cronin K, Gee-Lai V, Deyton M, Barr M, Holle TV, Macintyre AN, Stover E, Feldman J, Hauser BM, Caradonna TM, Scobey TD, Rountree W, Wang Y, Moody MA, Cain DW, DeMarco CT, Denny T, Woods CW, Petzold EW, Schmidt AG, Teng IT, Zhou T, Kwong PD, Mascola JR, Graham BS, Moore IN, Seder R, Andersen H, Lewis MG, Montefiori DC, Sempowski GD, Baric RS, Acharya P, Haynes BF, and Saunders KO

Abstract

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro , while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.

Published
2021
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31. SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys.

Author

Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Edwards RJ, Gobeil S, Barr M, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Rountree RW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Oguin TH, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Acharya P, Andersen H, Lewis MG, Moore IN, Montefiori DC, Baric RS, and Haynes BF

Abstract

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

Published
2021
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32. Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

Author

Denny TN, Andrews L, Bonsignori M, Cavanaugh K, Datto MB, Deckard A, DeMarco CT, DeNaeyer N, Epling CA, Gurley T, Haase SB, Hallberg C, Harer J, Kneifel CL, Lee MJ, Louzao R, Moody MA, Moore Z, Polage CR, Puglin J, Spotts PH, Vaughn JA, and Wolfe CR

Subjects
Betacoronavirus isolation & purification, COVID-19, COVID-19 Testing, COVID-19 Vaccines, Coronavirus Infections prevention & control, Humans, North Carolina epidemiology, Pandemics prevention & control, Pneumonia, Viral prevention & control, Program Development, SARS-CoV-2, Universities, Viral Load, Asymptomatic Diseases epidemiology, Clinical Laboratory Techniques methods, Coronavirus Infections diagnosis, Coronavirus Infections epidemiology, Pneumonia, Viral diagnosis, Pneumonia, Viral epidemiology, Public Health Surveillance methods
Abstract

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Published
2020
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33. SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

Author

Hurst JH, Heston SM, Chambers HN, Cunningham HM, Price MJ, Suarez L, Crew CG, Bose S, Aquino JN, Carr ST, Griffin SM, Smith SH, Jenkins K, Pfeiffer TS, Rodriguez J, DeMarco CT, De Naeyer NA, Gurley TC, Louzao R, Cunningham CK, Steinbach WJ, Denny TN, Lugo DJ, Moody MA, Permar SR, Rotta AT, Turner NA, Walter EB, Woods CW, and Kelly MS

Abstract

Background: Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children., Methods: We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay., Results: Of 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children., Conclusions: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.

Published
2020
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34. Selective uncoupling of G alpha 12 from Rho-mediated signaling.

Author

Meigs TE, Juneja J, DeMarco CT, Stemmle LN, Kaplan DD, and Casey PJ

Subjects
Cadherins physiology, Cell Line, Humans, Protein Binding physiology, Rho Guanine Nucleotide Exchange Factors, GTP-Binding Protein alpha Subunits, G12-G13 metabolism, Guanine Nucleotide Exchange Factors physiology, Signal Transduction physiology
Abstract

The heterotrimeric G protein G(12) has been implicated in such cellular regulatory processes as cytoskeletal rearrangement, cell-cell adhesion, and oncogenic transformation. Although the activated alpha-subunit of G(12) has been shown to interact directly with a number of protein effectors, the roles of many of these protein-protein interactions in G(12)-mediated cell physiology are poorly understood. To begin dissecting the specific cellular pathways engaged upon G(12) activation, we produced a series of substitution mutants in the regions of Galpha(12) predicted to play a role in effector binding. Here we report the identification and characterization of an altered form of Galpha(12) that is functionally uncoupled from signaling through the monomeric G protein Rho, a protein known to propagate several Galpha(12)-mediated signals. This mutant of Galpha(12) fails to bind the Rho-specific guanine nucleotide exchange factors p115RhoGEF and LARG (leukemia-associated RhoGEF), fails to stimulate Rho-dependent transcriptional activation, and fails to trigger activation of RhoA and the Rho-mediated cellular responses of cell rounding and c-jun N-terminal kinase activation. Importantly, this mutant of Galpha(12) retains coupling to the effector protein E-cadherin, as evidenced by its ability both to bind E-cadherin in vitro and to disrupt E-cadherin-mediated cell-cell adhesion. Furthermore, this mutant retains the ability to trigger beta-catenin release from the cytoplasmic domain of cadherin. This identification of a variant of Galpha(12) that is selectively uncoupled from one signaling pathway while retaining signaling capacity through a separate pathway will facilitate investigations into the mechanisms through which G(12) proteins mediate diverse biological responses.

Published
2005
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