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1. A non-human primate model for human norovirus infection

Author

Rimkute, Inga, Chaimongkol, Natthawan, Woods, Kamron D., Nagata, Bianca M., Darko, Samuel, Gudbole, Sucheta, Henry, Amy R., Sosnovtsev, Stanislav V., Olia, Adam S., Verardi, Raffaello, Bok, Karin, Todd, John-Paul, Woodward, Ruth, Kwong, Peter D., Douek, Daniel C., Alves, Derron A., Green, Kim Y., and Roederer, Mario

Published
2024
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4. 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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6. mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

Author

Corbett, Kizzmekia S., Werner, Anne P., Connell, Sarah O’, Gagne, Matthew, Lai, Lilin, Moliva, Juan I., Flynn, Barbara, Choi, Angela, Koch, Matthew, Foulds, Kathryn E., Andrew, Shayne F., Flebbe, Dillon R., Lamb, Evan, Nurmukhambetova, Saule T., Provost, Samantha J., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Ry, Alex Van, Flinchbaugh, Zackery, Johnston, Timothy S., Mokhtari, Elham Bayat, Mudvari, Prakriti, Henry, Amy R., Laboune, Farida, Chang, Becky, Porto, Maciel, Wear, Jaclyn, Alvarado, Gabriela S., Boyoglu-Barnum, Seyhan, Todd, John-Paul M., Bart, Bridget, Cook, Anthony, Dodson, Alan, Pessaint, Laurent, Steingrebe, Katelyn, Elbashir, Sayda, Sriparna, Manjari, Pekosz, Andrew, Andersen, Hanne, Wu, Kai, Edwards, Darin K., Kar, Swagata, Lewis, Mark G., Boritz, Eli, Moore, Ian N., Carfi, Andrea, Suthar, Mehul S., McDermott, Adrian, Roederer, Mario, Nason, Martha C., Sullivan, Nancy J., Douek, Daniel C., Graham, Barney S., and Seder, Robert A.

Published
2021
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7. 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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8. 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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11. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

Author

Corbett, Kizzmekia S., Edwards, Darin K., Leist, Sarah R., Abiona, Olubukola M., Boyoglu-Barnum, Seyhan, Gillespie, Rebecca A., Himansu, Sunny, Schäfer, Alexandra, Ziwawo, Cynthia T., DiPiazza, Anthony T., Dinnon, Kenneth H., Elbashir, Sayda M., Shaw, Christine A., Woods, Angela, Fritch, Ethan J., Martinez, David R., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Hutchinson, Geoffrey B., Wu, Kai, Henry, Carole, Bahl, Kapil, Garcia-Dominguez, Dario, Ma, LingZhi, Renzi, Isabella, Kong, Wing-Pui, Schmidt, Stephen D., Wang, Lingshu, Zhang, Yi, Phung, Emily, Chang, Lauren A., Loomis, Rebecca J., Altaras, Nedim Emil, Narayanan, Elisabeth, Metkar, Mihir, Presnyak, Vlad, Liu, Cuiping, Louder, Mark K., Shi, Wei, Leung, Kwanyee, Yang, Eun Sung, West, Ande, Gully, Kendra L., Stevens, Laura J., Wang, Nianshuang, Wrapp, Daniel, Doria-Rose, Nicole A., Stewart-Jones, Guillaume, Bennett, Hamilton, Alvarado, Gabriela S., Nason, Martha C., Ruckwardt, Tracy J., McLellan, Jason S., Denison, Mark R., Chappell, James D., Moore, Ian N., Morabito, Kaitlyn M., Mascola, John R., Baric, Ralph S., Carfi, Andrea, and Graham, Barney S.

Published
2020
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12. Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates

Author

Moliva, Juan I, primary, Andrew, Shayne F, additional, Flynn, Barbara J, additional, Wagner, Danielle A, additional, Foulds, Kathryn E, additional, Gagne, Matthew, additional, Flebbe, Dillon R, additional, Lamb, Evan, additional, Provost, Samantha, additional, Marquez, Josue, additional, Mychalowych, Anna, additional, Lorag, Cynthia, additional, Honeycutt, Christopher Cole, additional, Burnett, Matthew R, additional, McCormick, Lauren, additional, Henry, Amy R, additional, Godbole, Sucheta, additional, Davis-Gardner, Meredith E, additional, Minai, Mahnaz, additional, Bok, Kevin W, additional, Nagata, Bianca M, additional, Todd, John-Paul M, additional, McCarthy, Elizabeth, additional, Dodson, Alan, additional, Kouneski, Katelyn, additional, Cook, Anthony, additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Valentin, Daniel, additional, Young, Steve, additional, Littman, Yoav, additional, Boon, Adrianus C. M., additional, Suthar, Mehul S, additional, Lewis, Mark G, additional, Andersen, Hanne, additional, Alves, Derron A, additional, Woodward, Ruth, additional, Leuzzi, Adriano, additional, Vitelli, Alessandra, additional, Colloca, Stefano, additional, Folgori, Antonella, additional, Raggiolli, Angelo, additional, Capone, Stefania, additional, Nason, Martha C, additional, Douek, Daniel, additional, Roederer, Mario, additional, Seder, Robert A, additional, and Sullivan, Nancy J, additional

Published
2023
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13. Human norovirus targets enteroendocrine epithelial cells in the small intestine

Author

Green, Kim Y., Kaufman, Stuart S., Nagata, Bianca M., Chaimongkol, Natthawan, Kim, Daniel Y., Levenson, Eric A., Tin, Christine M., Yardley, Allison Behrle, Johnson, Jordan A., Barletta, Ana Beatriz F., Khan, Khalid M., Yazigi, Nada A., Subramanian, Sukanya, Moturi, Sangeetha R., Fishbein, Thomas M., Moore, Ian N., and Sosnovtsev, Stanislav V.

Published
2020
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14. Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection

Author

Meyer, Michelle, Wang, Yuan, Edwards, Darin, Smith, Gregory R., Rubenstein, Aliza B., Ramanathan, Palaniappan, Mire, Chad E., Pietzsch, Colette, Chen, Xi, Ge, Yongchao, Cheng, Wan Sze, Henry, Carole, Woods, Angela, Ma, LingZhi, Stewart-Jones, Guillaume B.E., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Periasamy, Sivakumar, Shi, Pei-Yong, Graham, Barney S., Moore, Ian N., Ramos, Irene, Troyanskaya, Olga G., Zaslavsky, Elena, Carfi, Andrea, Sealfon, Stuart C., and Bukreyev, Alexander

Subjects
Immunological research, Lung diseases -- Models -- Development and progression -- Prevention, Immune response -- Research, Messenger RNA -- Health aspects -- Physiological aspects, Leukocytes -- Health aspects -- Physiological aspects, Hamsters -- Physiological aspects, Health care industry
Abstract

The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibits severe SARS-CoV-2 disease similar to that in hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and nonhuman primates, low-level virus replication in mRNA-1273-vaccinated hamsters coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high-resolution analysis that is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock- vaccinated hamsters. Our results support the use of mRNA-1273 in a 2-dose schedule and provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2., Introduction When the World Health Organization declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a global pandemic in March 2020, phase I clinical trials on the most promising vaccine candidates [...]

Published
2021
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16. An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant replication in rhesus macaques

Author

Sui, Yongjun, primary, Li, Jianping, additional, Andersen, Hanne, additional, Zhang, Roushu, additional, Prabhu, Sunaina K, additional, Hoang, Tanya, additional, Venzon, David, additional, Cook, Anthony, additional, Brown, Renita, additional, Teow, Elyse, additional, Velasco, Jason, additional, Pessaint, Laurent, additional, Moore, Ian N, additional, Lagenaur, Laurel, additional, Talton, Jim, additional, Breed, Matthew W, additional, Kramer, Josh, additional, Bock, Kevin W, additional, Minai, Mahnaz, additional, Nagata, Bianca M, additional, Choo-Wosoba, Hyoyoung, additional, Lewis, Mark G, additional, Wang, Lai-Xi, additional, and Berzofsky, Jay A, additional

Published
2022
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17. mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

Author

Gagne, Matthew, primary, Moliva, Juan I., additional, Foulds, Kathryn E., additional, Andrew, Shayne F., additional, Flynn, Barbara J., additional, Werner, Anne P., additional, Wagner, Danielle A., additional, Teng, I-Ting, additional, Lin, Bob C., additional, Moore, Christopher, additional, Jean-Baptiste, Nazaire, additional, Carroll, Robin, additional, Foster, Stephanie L., additional, Patel, Mit, additional, Ellis, Madison, additional, Edara, Venkata-Viswanadh, additional, Maldonado, Nahara Vargas, additional, Minai, Mahnaz, additional, McCormick, Lauren, additional, Honeycutt, Christopher Cole, additional, Nagata, Bianca M., additional, Bock, Kevin W., additional, Dulan, Caitlyn N.M., additional, Cordon, Jamilet, additional, Flebbe, Dillon R., additional, Todd, John-Paul M., additional, McCarthy, Elizabeth, additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Narvaez, Brandon, additional, Valentin, Daniel, additional, Cook, Anthony, additional, Dodson, Alan, additional, Steingrebe, Katelyn, additional, Nurmukhambetova, Saule T., additional, Godbole, Sucheta, additional, Henry, Amy R., additional, Laboune, Farida, additional, Roberts-Torres, Jesmine, additional, Lorang, Cynthia G., additional, Amin, Shivani, additional, Trost, Jessica, additional, Naisan, Mursal, additional, Basappa, Manjula, additional, Willis, Jacquelyn, additional, Wang, Lingshu, additional, Shi, Wei, additional, Doria-Rose, Nicole A., additional, Zhang, Yi, additional, Yang, Eun Sung, additional, Leung, Kwanyee, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Olia, Adam S., additional, Liu, Cuiping, additional, Harris, Darcy R., additional, Chuang, Gwo-Yu, additional, Stewart-Jones, Guillaume, additional, Renzi, Isabella, additional, Lai, Yen-Ting, additional, Malinowski, Agata, additional, Wu, Kai, additional, Mascola, John R., additional, Carfi, Andrea, additional, Kwong, Peter D., additional, Edwards, Darin K., additional, Lewis, Mark G., additional, Andersen, Hanne, additional, Corbett, Kizzmekia S., additional, Nason, Martha C., additional, McDermott, Adrian B., additional, Suthar, Mehul S., additional, Moore, Ian N., additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, and Seder, Robert A., additional

Published
2022
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18. mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron

Author

Gagne, Matthew, primary, Moliva, Juan I., additional, Foulds, Kathryn E., additional, Andrew, Shayne F., additional, Flynn, Barbara J., additional, Werner, Anne P., additional, Wagner, Danielle A., additional, Teng, I-Ting, additional, Lin, Bob C., additional, Moore, Christopher, additional, Jean-Baptiste, Nazaire, additional, Carroll, Robin, additional, Foster, Stephanie L., additional, Patel, Mit, additional, Ellis, Madison, additional, Edara, Venkata-Viswanadh, additional, Maldonado, Nahara Vargas, additional, Minai, Mahnaz, additional, McCormick, Lauren, additional, Honeycutt, Christopher Cole, additional, Nagata, Bianca M., additional, Bock, Kevin W., additional, Dulan, Caitlyn N. M., additional, Cordon, Jamilet, additional, Todd, John-Paul M., additional, McCarthy, Elizabeth, additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Narvaez, Brandon, additional, Valentin, Daniel, additional, Cook, Anthony, additional, Dodson, Alan, additional, Steingrebe, Katelyn, additional, Flebbe, Dillon R., additional, Nurmukhambetova, Saule T., additional, Godbole, Sucheta, additional, Henry, Amy R., additional, Laboune, Farida, additional, Roberts-Torres, Jesmine, additional, Lorang, Cynthia G., additional, Amin, Shivani, additional, Trost, Jessica, additional, Naisan, Mursal, additional, Basappa, Manjula, additional, Willis, Jacquelyn, additional, Wang, Lingshu, additional, Shi, Wei, additional, Doria-Rose, Nicole A., additional, Olia, Adam S., additional, Liu, Cuiping, additional, Harris, Darcy R., additional, Carfi, Andrea, additional, Mascola, John R., additional, Kwong, Peter D., additional, Edwards, Darin K., additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Corbett, Kizzmekia S., additional, Nason, Martha C., additional, McDermott, Adrian B., additional, Suthar, Mehul S., additional, Moore, Ian N., additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, and Seder, Robert A., additional

Published
2022
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19. 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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20. Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung

Author

Gagne, Matthew, primary, Corbett, Kizzmekia S., additional, Flynn, Barbara J., additional, Foulds, Kathryn E., additional, Wagner, Danielle A., additional, Andrew, Shayne F., additional, Todd, John-Paul M., additional, Honeycutt, Christopher Cole, additional, McCormick, Lauren, additional, Nurmukhambetova, Saule T., additional, Davis-Gardner, Meredith E., additional, Pessaint, Laurent, additional, Bock, Kevin W., additional, Nagata, Bianca M., additional, Minai, Mahnaz, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Tucker, Courtney, additional, Lorang, Cynthia G., additional, Zhao, Bingchun, additional, McCarthy, Elizabeth, additional, Cook, Anthony, additional, Dodson, Alan, additional, Teng, I-Ting, additional, Mudvari, Prakriti, additional, Roberts-Torres, Jesmine, additional, Laboune, Farida, additional, Wang, Lingshu, additional, Goode, Adrienne, additional, Kar, Swagata, additional, Boyoglu-Barnum, Seyhan, additional, Yang, Eun Sung, additional, Shi, Wei, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Carfi, Andrea, additional, Mascola, John R., additional, Boritz, Eli A., additional, Edwards, Darin K., additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Graham, Barney S., additional, Roederer, Mario, additional, Moore, Ian N., additional, Nason, Martha C., additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, and Seder, Robert A., additional

Published
2022
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21. Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine–boosted nonhuman primates

Author

Corbett, Kizzmekia S., primary, Gagne, Matthew, additional, Wagner, Danielle A., additional, O’ Connell, Sarah, additional, Narpala, Sandeep R., additional, Flebbe, Dillon R., additional, Andrew, Shayne F., additional, Davis, Rachel L., additional, Flynn, Barbara, additional, Johnston, Timothy S., additional, Stringham, Christopher D., additional, Lai, Lilin, additional, Valentin, Daniel, additional, Van Ry, Alex, additional, Flinchbaugh, Zackery, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Sriparna, Manjari, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Tucker, Courtney, additional, Choi, Angela, additional, Koch, Matthew, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Alvarado, Gabriela S., additional, Henry, Amy R., additional, Laboune, Farida, additional, Schramm, Chaim A., additional, Zhang, Yi, additional, Yang, Eun Sung, additional, Wang, Lingshu, additional, Choe, Misook, additional, Boyoglu-Barnum, Seyhan, additional, Wei, Shi, additional, Lamb, Evan, additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Donaldson, Mitzi M., additional, Marquez, Josue, additional, Todd, John-Paul M., additional, Cook, Anthony, additional, Dodson, Alan, additional, Pekosz, Andrew, additional, Boritz, Eli, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Pessaint, Laurent, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Misasi, John, additional, Wu, Kai, additional, Carfi, Andrea, additional, Nason, Martha C., additional, Mascola, John, additional, Moore, Ian N., additional, Edwards, Darin K., additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Roederer, Mario, additional, McDermott, Adrian, additional, Douek, Daniel C., additional, Sullivan, Nancy J., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
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22. Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway

Author

Gagne, Matthew, primary, Corbett, Kizzmekia S., additional, Flynn, Barbara J., additional, Foulds, Kathryn E., additional, Wagner, Danielle A., additional, Andrew, Shayne F., additional, Todd, John-Paul M., additional, Honeycutt, Christopher Cole, additional, McCormick, Lauren, additional, Nurmukhambetova, Saule T., additional, Davis-Gardner, Meredith E., additional, Pessaint, Laurent, additional, Bock, Kevin W., additional, Nagata, Bianca M., additional, Minai, Mahnaz, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Tucker, Courtney, additional, Lorang, Cynthia G., additional, Zhao, Bingchun, additional, McCarthy, Elizabeth, additional, Cook, Anthony, additional, Dodson, Alan, additional, Mudvari, Prakriti, additional, Roberts-Torres, Jesmine, additional, Laboune, Farida, additional, Wang, Lingshu, additional, Goode, Adrienne, additional, Kar, Swagata, additional, Boyoglu-Barnum, Seyhan, additional, Yang, Eun Sung, additional, Shi, Wei, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Carfi, Andrea, additional, Mascola, John R., additional, Boritz, Eli A., additional, Edwards, Darin K., additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Graham, Barney S., additional, Roederer, Mario, additional, Moore, Ian N., additional, Nason, Martha C., additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, and Seder, Robert A., additional

Published
2021
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23. An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques

Author

Sui, Yongjun, primary, Li, Jianping, additional, Andersen, Hanne, additional, Zhang, Roushu, additional, Prabhu, Sunaina Kiran, additional, Hoang, Tanya, additional, Venzon, David, additional, Cook, Anthony, additional, Brown, Renita, additional, Teow, Elyse, additional, Velasco, Jason, additional, Pessaint, Laurent, additional, Moore, Ian N., additional, Lagenaur, Laurel, additional, Talton, Jim, additional, Breed, Matthew W., additional, Kramer, Josh, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Choo-Wosoba, Hyoyoung, additional, Lewis, Mark G., additional, Wang, Lai-Xi, additional, and Berzofsky, Jay A., additional

Published
2021
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24. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Author

Corbett, Kizzmekia S., primary, Nason, Martha C., additional, Flach, Britta, additional, Gagne, Matthew, additional, O’Connell, Sarah, additional, Johnston, Timothy S., additional, Shah, Shruti N., additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, McDanal, Charlene, additional, Francica, Joseph R., additional, Flynn, Barbara, additional, Wu, Kai, additional, Choi, Angela, additional, Koch, Matthew, additional, Abiona, Olubukola M., additional, Werner, Anne P., additional, Moliva, Juan I., additional, Andrew, Shayne F., additional, Donaldson, Mitzi M., additional, Fintzi, Jonathan, additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Noe, Amy T., additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Cook, Anthony, additional, Dodson, Alan, additional, Faudree, Andrew, additional, Greenhouse, Jack, additional, Kar, Swagata, additional, Pessaint, Laurent, additional, Porto, Maciel, additional, Steingrebe, Katelyn, additional, Valentin, Daniel, additional, Zouantcha, Serge, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, van de Wetering, Renee, additional, Boyoglu-Barnum, Seyhan, additional, Leung, Kwanyee, additional, Shi, Wei, additional, Yang, Eun Sung, additional, Zhang, Yi, additional, Todd, John-Paul M., additional, Wang, Lingshu, additional, Alvarado, Gabriela S., additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Edwards, Darin K., additional, Mascola, John R., additional, Moore, Ian N., additional, Lewis, Mark G., additional, Carfi, Andrea, additional, Montefiori, David, additional, Suthar, Mehul S., additional, McDermott, Adrian, additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
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25. Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Gagne, Matthew, additional, Wagner, Danielle A., additional, Connell, Sarah O’, additional, Narpala, Sandeep R., additional, Flebbe, Dillon R., additional, Andrew, Shayne F., additional, Davis, Rachel L., additional, Flynn, Barbara, additional, Johnston, Timothy S., additional, Stringham, Christopher, additional, Lai, Lilin, additional, Valentin, Daniel, additional, Van Ry, Alex, additional, Flinchbaugh, Zackery, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Sriparna, Manjari, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Tucker, Courtney, additional, Choi, Angela, additional, Koch, Matthew, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Alvarado, Gabriela S., additional, Henry, Amy R., additional, Laboune, Farida, additional, Schramm, Chaim A., additional, Zhang, Yi, additional, Wang, Lingshu, additional, Choe, Misook, additional, Boyoglu-Barnum, Seyhan, additional, Shi, Wei, additional, Lamb, Evan, additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Donaldson, Mitzi M., additional, Marquez, Josue, additional, Todd, John-Paul M., additional, Cook, Anthony, additional, Dodson, Alan, additional, Pekosz, Andrew, additional, Boritz, Eli, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Pessaint, Laurent, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Misasi, John, additional, Wu, Kai, additional, Carfi, Andrea, additional, Nason, Martha C., additional, Mascola, John, additional, Moore, Ian N., additional, Edwards, Darin K., additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Roederer, Mario, additional, McDermott, Adrian, additional, Douek, Daniel C., additional, Sullivan, Nancy J., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
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26. 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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27. COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

Author

DiPiazza, Anthony T., primary, Leist, Sarah R., additional, Abiona, Olubukola M., additional, Moliva, Juan I., additional, Werner, Anne, additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Bock, Kevin W., additional, Phung, Emily, additional, Schäfer, Alexandra, additional, Dinnon, Kenneth H., additional, Chang, Lauren A., additional, Loomis, Rebecca J., additional, Boyoglu-Barnum, Seyhan, additional, Alvarado, Gabriela S., additional, Sullivan, Nancy J., additional, Edwards, Darin K., additional, Morabito, Kaitlyn M., additional, Mascola, John R., additional, Carfi, Andrea, additional, Corbett, Kizzmekia S., additional, Moore, Ian N., additional, Baric, Ralph S., additional, Graham, Barney S., additional, and Ruckwardt, Tracy J., additional

Published
2021
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28. Short stature and combined immunodeficiency associated with mutations in RGS10

Author

Chinn, Ivan K., primary, Xie, Zhihui, additional, Chan, Eunice C., additional, Nagata, Bianca M., additional, Koval, Alexey, additional, Chen, Wei-Sheng, additional, Zhang, Fan, additional, Ganesan, Sundar, additional, Hong, Diana N., additional, Suzuki, Motoshi, additional, Nardone, Glenn, additional, Moore, Ian N., additional, Katanaev, Vladimir L., additional, Balazs, Andrea E., additional, Liu, Chengyu, additional, Lupski, James R., additional, Orange, Jordan S., additional, and Druey, Kirk M., additional

Published
2021
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29. 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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30. Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Werner, Anne P., additional, O’ Connell, Sarah, additional, Gagne, Matthew, additional, Lai, Lilin, additional, Moliva, Juan I., additional, Flynn, Barbara, additional, Choi, Angela, additional, Koch, Matthew, additional, Foulds, Kathryn E., additional, Andrew, Shayne F., additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Van Ry, Alex, additional, Flinchbaugh, Zackery, additional, Johnston, Timothy S., additional, Mokhtari, Elham Bayat, additional, Mudvari, Prakriti, additional, Henry, Amy R., additional, Laboune, Farida, additional, Chang, Becky, additional, Porto, Maciel, additional, Wear, Jaclyn, additional, Alvarado, Gabriela S., additional, Boyoglu-Barnum, Seyhan, additional, Todd, John-Paul M., additional, Bart, Bridget, additional, Cook, Anthony, additional, Dodson, Alan, additional, Pessaint, Laurent, additional, Steingrebe, Katelyn, additional, Elbashir, Sayda, additional, Andersen, Hanne, additional, Wu, Kai, additional, Edwards, Darin K., additional, Kar, Swagata, additional, Lewis, Mark G., additional, Bortiz, Eli, additional, Moore, Ian N., additional, Carfi, Andrea, additional, Suthar, Mehul S., additional, McDermott, Adrian, additional, Roederer, Mario, additional, Nason, Martha C., additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
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31. Protection against SARS-CoV-2 infection by a mucosal vaccine in rhesus macaques

Author

Sui, Yongjun, primary, Li, Jianping, additional, Zhang, Roushu, additional, Prabhu, Sunaina Kiran, additional, Andersen, Hanne, additional, Venzon, David, additional, Cook, Anthony, additional, Brown, Renita, additional, Teow, Elyse, additional, Velasco, Jason, additional, Greenhouse, Jack, additional, Putman-Taylor, Tammy, additional, Campbell, Tracey-Ann, additional, Pessaint, Laurent, additional, Moore, Ian N., additional, Lagenaur, Laurel, additional, Talton, Jim, additional, Breed, Matthew W., additional, Kramer, Josh, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Lewis, Mark G., additional, Wang, Lai-Xi, additional, and Berzofsky, Jay A., additional

Published
2021
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32. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Nason, Martha C., additional, Flach, Britta, additional, Gagne, Matthew, additional, O’ Connell, Sarah, additional, Johnston, Timothy S., additional, Shah, Shruti N., additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, McDanal, Charlene, additional, Francica, Joseph R., additional, Flynn, Barbara, additional, Wu, Kai, additional, Choi, Angela, additional, Koch, Matthew, additional, Abiona, Olubukola M., additional, Werner, Anne P., additional, Alvarado, Gabriela S., additional, Andrew, Shayne F., additional, Donaldson, Mitzi M., additional, Fintzi, Jonathan, additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Noe, Amy T., additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Cook, Anthony, additional, Dodson, Alan, additional, Faudree, Andrew, additional, Greenhouse, Jack, additional, Kar, Swagata, additional, Pessaint, Laurent, additional, Porto, Maciel, additional, Steingrebe, Katelyn, additional, Valentin, Daniel, additional, Zouantcha, Serge, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Moliva, Juan I., additional, van de Wetering, Renee, additional, Boyoglu-Barnum, Seyhan, additional, Leung, Kwanyee, additional, Shi, Wei, additional, Yang, Eun Sung, additional, Zhang, Yi, additional, Todd, John-Paul M., additional, Wang, Lingshu, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Edwards, Darin K., additional, Mascola, John R., additional, Moore, Ian N., additional, Lewis, Mark G., additional, Carfi, Andrea, additional, Montefiori, David, additional, Suthar, Mehul S., additional, McDermott, Adrian, additional, Sullivan, Nancy J., additional, Roederer, Mario, additional, Douek, Daniel C., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
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33. mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge

Author

Meyer, Michelle, primary, Wang, Yuan, additional, Edwards, Darin, additional, Smith, Gregory R., additional, Rubenstein, Aliza B., additional, Ramanathan, Palaniappan, additional, Mire, Chad E., additional, Pietzsch, Colette, additional, Chen, Xi, additional, Ge, Yongchao, additional, Cheng, Wan Sze, additional, Henry, Carole, additional, Woods, Angela, additional, Ma, LingZhi, additional, Stewart-Jones, Guillaume B. E., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Periasamy, Sivakumar, additional, Shi, Pei-Yong, additional, Graham, Barney S., additional, Moore, Ian N., additional, Ramos, Irene, additional, Troyanskaya, Olga G., additional, Zaslavsky, Elena, additional, Carfi, Andrea, additional, Sealfon, Stuart C., additional, and Bukreyev, Alexander, additional

Published
2021
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34. 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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35. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Flynn, Barbara, additional, Foulds, Kathryn E., additional, Francica, Joseph R., additional, Boyoglu-Barnum, Seyhan, additional, Werner, Anne P., additional, Flach, Britta, additional, O’Connell, Sarah, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Andersen, Hanne, additional, Martinez, David R., additional, Noe, Amy T., additional, Douek, Naomi, additional, Donaldson, Mitzi M., additional, Nji, Nadesh N., additional, Alvarado, Gabriela S., additional, Edwards, Darin K., additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Doria-Rose, Nicole A., additional, Lin, Bob C., additional, Louder, Mark K., additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Phung, Emily, additional, Chang, Lauren A., additional, Yap, Christina, additional, Todd, John-Paul M., additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Browne, Shanai, additional, Greenhouse, Jack, additional, Putman-Taylor, Tammy, additional, Strasbaugh, Amanda, additional, Campbell, Tracey-Ann, additional, Cook, Anthony, additional, Dodson, Alan, additional, Steingrebe, Katelyn, additional, Shi, Wei, additional, Zhang, Yi, additional, Abiona, Olubukola M., additional, Wang, Lingshu, additional, Pegu, Amarendra, additional, Yang, Eun Sung, additional, Leung, Kwanyee, additional, Zhou, Tongqing, additional, Teng, I-Ting, additional, Widge, Alicia, additional, Gordon, Ingelise, additional, Novik, Laura, additional, Gillespie, Rebecca A., additional, Loomis, Rebecca J., additional, Moliva, Juan I., additional, Stewart-Jones, Guillaume, additional, Himansu, Sunny, additional, Kong, Wing-Pui, additional, Nason, Martha C., additional, Morabito, Kaitlyn M., additional, Ruckwardt, Tracy J., additional, Ledgerwood, Julie E., additional, Gaudinski, Martin R., additional, Kwong, Peter D., additional, Mascola, John R., additional, Carfi, Andrea, additional, Lewis, Mark G., additional, Baric, Ralph S., additional, McDermott, Adrian, additional, Moore, Ian N., additional, Sullivan, Nancy J., additional, Roederer, Mario, additional, Seder, Robert A., additional, and Graham, Barney S., additional

Published
2020
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36. Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance

Author

DeSouza-Vieira, Thiago, primary, Iniguez, Eva, additional, Serafim, Tiago D., additional, de Castro, Waldionê, additional, Karmakar, Subir, additional, Disotuar, Maria M., additional, Cecilio, Pedro, additional, Lacsina, Joshua R., additional, Meneses, Claudio, additional, Nagata, Bianca M., additional, Cardoso, Silvia, additional, Sonenshine, Daniel E., additional, Moore, Ian N., additional, Borges, Valeria M., additional, Dey, Ranadhir, additional, Soares, Miguel P., additional, Nakhasi, Hira L., additional, Oliveira, Fabiano, additional, Valenzuela, Jesus G., additional, and Kamhawi, Shaden, additional

Published
2020
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37. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

Author

Corbett, Kizzmekia S., primary, Edwards, Darin, additional, Leist, Sarah R., additional, Abiona, Olubukola M., additional, Boyoglu-Barnum, Seyhan, additional, Gillespie, Rebecca A., additional, Himansu, Sunny, additional, Schäfer, Alexandra, additional, Ziwawo, Cynthia T., additional, DiPiazza, Anthony T., additional, Dinnon, Kenneth H., additional, Elbashir, Sayda M., additional, Shaw, Christine A., additional, Woods, Angela, additional, Fritch, Ethan J., additional, Martinez, David R., additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Hutchinson, Geoffrey B., additional, Bahl, Kapil, additional, Garcia-Dominguez, Dario, additional, Ma, LingZhi, additional, Renzi, Isabella, additional, Kong, Wing-Pui, additional, Schmidt, Stephen D., additional, Wang, Lingshu, additional, Zhang, Yi, additional, Stevens, Laura J., additional, Phung, Emily, additional, Chang, Lauren A., additional, Loomis, Rebecca J., additional, Altaras, Nedim Emil, additional, Narayanan, Elisabeth, additional, Metkar, Mihir, additional, Presnyak, Vlad, additional, Liu, Catherine, additional, Louder, Mark K., additional, Shi, Wei, additional, Leung, Kwanyee, additional, Yang, Eun Sung, additional, West, Ande, additional, Gully, Kendra L., additional, Wang, Nianshuang, additional, Wrapp, Daniel, additional, Doria-Rose, Nicole A., additional, Stewart-Jones, Guillaume, additional, Bennett, Hamilton, additional, Nason, Martha C., additional, Ruckwardt, Tracy J., additional, McLellan, Jason S., additional, Denison, Mark R., additional, Chappell, James D., additional, Moore, Ian N., additional, Morabito, Kaitlyn M., additional, Mascola, John R., additional, Baric, Ralph S., additional, Carfi, Andrea, additional, and Graham, Barney S., additional

Published
2020
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38. Heme Oxygenase-1 Induction by Blood Feeding Arthropods Controls Skin Inflammation and Promotes Tolerance to Pathogens

Author

DeSouza-Vieira, Thiago, primary, Iniguez, Eva, additional, Serafim, Tiago D., additional, de Castro, Waldionê, additional, Karmakar, Subir, additional, Disotuar, Maria M., additional, Cecilio, Pedro, additional, Lacsina, Joshua R., additional, Meneses, Claudio, additional, Nagata, Bianca M., additional, Cardoso, Silvia, additional, Sonenshine, Daniel E., additional, Moore, Ian N., additional, Borges, Valeria M., additional, Dey, Ranadhir, additional, Soares, Miguel, additional, Nakhasi, Hira, additional, Oliveira, Fabiano, additional, Valenzuela, Jesus G., additional, and Kamhawi, Shaden, additional

Published
2020
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40. Reconstitution of norovirus-specific T cell responses following hematopoietic stem cell transplantation in patients with inborn errors of immunity and chronic norovirus infection.

Author

Durkee-Shock J, Cohen A, Maghzian N, Pezzella G, Jensen-Wachspress M, Hostal A, Barton K, Gangler K, Dávila Saldaña BJ, Chaimongkol N, Bollard CM, Sosnovtsev SV, Cohen J, Nagata BM, Alves DA, Ghosh R, Seifert BA, Freeman A, Gonzalez C, Notarangelo LD, Green KY, and Keller MD

Abstract

Background: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists., Methods: Two patients with inborn errors of immunity, X- linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T cell (NST) response, B cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant setting (HSCT) before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing., Results: The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in one patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-vs-host-disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T cell compartments which recognized multiple norovirus structural and non-structural viral antigens. T cell responses were minimal during active CNI but detectable after resolution. Mapping of norovirus-specific T cell responses between the patient with DOCK8 and his matched sibling donor were nearly identical. B cell reconstitution or new endogenous antibody production for IgA or IgG were not observed., Conclusion: This report is the first to demonstrate reconstitution of norovirus-specific T cell immunity after HSCT closely temporally aligned with clearance of CNI suggesting that cellular immunity is sufficient for norovirus clearance., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Published
2024
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41. 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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42. Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

Author

Moliva JI, Andrew SF, Flynn BJ, Wagner DA, Foulds KE, Gagne M, Flebbe DR, Lamb E, Provost S, Marquez J, Mychalowych A, Lorag CG, Honeycutt CC, Burnett MR, McCormick L, Henry AR, Godbole S, Davis-Gardner ME, Minai M, Bock KW, Nagata BM, Todd JM, McCarthy E, Dodson A, Kouneski K, Cook A, Pessaint L, Ry AV, Valentin D, Young S, Littman Y, Boon ACM, Suthar MS, Lewis MG, Andersen H, Alves DA, Woodward R, Leuzzi A, Vitelli A, Colloca S, Folgori A, Raggiolli A, Capone S, Nason MC, Douek DC, Roederer M, Seder RA, and Sullivan NJ

Abstract

SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways., Competing Interests: Declaration of interests M.R., N.J.S., and D.C.D. are inventors on U.S. Patent Application No. 63/147,419 entitled “Antibodies Targeting the Spike Protein of Coronaviruses”. L.P., A.V.R., D.V., A.C., A.D., M.G.L., and H.A. are employees of Bioqual, Inc. A.L., A.V., S.Co., A.F., A.R., and S.Ca. are employees of ReiThera Srl. S.Co. and A.F. are shareholders of Keires AG. A.V., S.Co. and A.R. are named inventors of the Patent Application No. 20183515.4 entitled “Gorilla Adenovirus Nucleic Acid- and Amino Acid-Sequences, Vectors Containing Same, and Uses Thereof”. The other authors declare no competing interests.

Published
2023
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43. 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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44. Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway.

Author

Gagne M, Corbett KS, Flynn BJ, Foulds KE, Wagner DA, Andrew SF, Todd JM, Honeycutt CC, McCormick L, Nurmukhambetova ST, Davis-Gardner ME, Pessaint L, Bock KW, Nagata BM, Minai M, Werner AP, Moliva JI, Tucker C, Lorang CG, Zhao B, McCarthy E, Cook A, Dodson A, Mudvari P, Roberts-Torres J, Laboune F, Wang L, Goode A, Kar S, Boyoglu-Barnum S, Yang ES, Shi W, Ploquin A, Doria-Rose N, Carfi A, Mascola JR, Boritz EA, Edwards DK, Andersen H, Lewis MG, Suthar MS, Graham BS, Roederer M, Moore IN, Nason MC, Sullivan NJ, Douek DC, and Seder RA

Abstract

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID 50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined ∼3-log 10 compared to control animals. In nasal swabs, sgRNA declined 1-log 10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

Published
2021
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45. Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates.

Author

Corbett KS, Gagne M, Wagner DA, Connell SO, Narpala SR, Flebbe DR, Andrew SF, Davis RL, Flynn B, Johnston TS, Stringham C, Lai L, Valentin D, Van Ry A, Flinchbaugh Z, Werner AP, Moliva JI, Sriparna M, O'Dell S, Schmidt SD, Tucker C, Choi A, Koch M, Bock KW, Minai M, Nagata BM, Alvarado GS, Henry AR, Laboune F, Schramm CA, Zhang Y, Wang L, Choe M, Boyoglu-Barnum S, Shi W, Lamb E, Nurmukhambetova ST, Provost SJ, Donaldson MM, Marquez J, Todd JM, Cook A, Dodson A, Pekosz A, Boritz E, Ploquin A, Doria-Rose N, Pessaint L, Andersen H, Foulds KE, Misasi J, Wu K, Carfi A, Nason MC, Mascola J, Moore IN, Edwards DK, Lewis MG, Suthar MS, Roederer M, McDermott A, Douek DC, Sullivan NJ, Graham BS, and Seder RA

Abstract

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.1.351 (beta or β) variant. Reciprocal ID 50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the β variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost β-specific reciprocal ID 50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the β variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations., One-Sentence Summary: mRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.

Published
2021
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46. Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates.

Author

Corbett KS, Werner AP, O' Connell S, Gagne M, Lai L, Moliva JI, Flynn B, Choi A, Koch M, Foulds KE, Andrew SF, Flebbe DR, Lamb E, Nurmukhambetova ST, Provost SJ, Bock KW, Minai M, Nagata BM, Van Ry A, Flinchbaugh Z, Johnston TS, Mokhtari EB, Mudvari P, Henry AR, Laboune F, Chang B, Porto M, Wear J, Alvarado GS, Boyoglu-Barnum S, Todd JM, Bart B, Cook A, Dodson A, Pessaint L, Steingrebe K, Elbashir S, Andersen H, Wu K, Edwards DK, Kar S, Lewis MG, Bortiz E, Moore IN, Carfi A, Suthar MS, McDermott A, Roederer M, Nason MC, Sullivan NJ, Douek DC, Graham BS, and Seder RA

Abstract

Background: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351., Methods: Nonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge., Results: Eight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID 50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log 10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge., Conclusions: Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.

Published
2021
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47. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates.

Author

Corbett KS, Nason MC, Flach B, Gagne M, O' Connell S, Johnston TS, Shah SN, Edara VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona OM, Werner AP, Alvarado GS, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, Faudree A, Greenhouse J, Kar S, Pessaint L, Porto M, Steingrebe K, Valentin D, Zouantcha S, Bock KW, Minai M, Nagata BM, Moliva JI, van de Wetering R, Boyoglu-Barnum S, Leung K, Shi W, Yang ES, Zhang Y, Todd JM, Wang L, Andersen H, Foulds KE, Edwards DK, Mascola JR, Moore IN, Lewis MG, Carfi A, Montefiori D, Suthar MS, McDermott A, Sullivan NJ, Roederer M, Douek DC, Graham BS, and Seder RA

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP., One-Sentence Summary: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Published
2021
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48. 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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49. mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge.

Author

Meyer M, Wang Y, Edwards D, Smith GR, Rubenstein AB, Ramanathan P, Mire CE, Pietzsch C, Chen X, Ge Y, Cheng WS, Henry C, Woods A, Ma L, Stewart-Jones GBE, Bock KW, Minai M, Nagata BM, Periasamy S, Shi PY, Graham BS, Moore IN, Ramos I, Troyanskaya OG, Zaslavsky E, Carfi A, Sealfon SC, and Bukreyev A

Abstract

The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.

Published
2021
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50. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness.

Author

Corbett KS, Edwards D, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, Himansu S, Schäfer A, Ziwawo CT, DiPiazza AT, Dinnon KH, Elbashir SM, Shaw CA, Woods A, Fritch EJ, Martinez DR, Bock KW, Minai M, Nagata BM, Hutchinson GB, Bahl K, Garcia-Dominguez D, Ma L, Renzi I, Kong WP, Schmidt SD, Wang L, Zhang Y, Stevens LJ, Phung E, Chang LA, Loomis RJ, Altaras NE, Narayanan E, Metkar M, Presnyak V, Liu C, Louder MK, Shi W, Leung K, Yang ES, West A, Gully KL, Wang N, Wrapp D, Doria-Rose NA, Stewart-Jones G, Bennett H, Nason MC, Ruckwardt TJ, McLellan JS, Denison MR, Chappell JD, Moore IN, Morabito KM, Mascola JR, Baric RS, Carfi A, and Graham BS

Abstract

A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation., Competing Interests: Competing Interest Declaration K.S.C., N.W., J.S.M., and B.S.G. are inventors on International Patent Application No. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” K.S.C., O.M.A., G.B.H., N.W., D.W., J.S.M, and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled “2019-nCoV Vaccine”. R.S.B. filed an invention report for the SARS-CoV-2 MA virus (UNC ref. #18752).

Published
2020
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