33 results on '"Pettie, Deleah"'
Search Results
2. Antigen spacing on protein nanoparticles influences antibody responses to vaccination
- Author
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Ellis, Daniel, Dosey, Annie, Boyoglu-Barnum, Seyhan, Park, Young-Jun, Gillespie, Rebecca, Syeda, Hubza, Hutchinson, Geoffrey B., Tsybovsky, Yaroslav, Murphy, Michael, Pettie, Deleah, Matheson, Nick, Chan, Sidney, Ueda, George, Fallas, Jorge A., Carter, Lauren, Graham, Barney S., Veesler, David, Kanekiyo, Masaru, and King, Neil P.
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- 2023
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3. Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens
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Kraft, John C., Pham, Minh N., Shehata, Laila, Brinkkemper, Mitch, Boyoglu-Barnum, Seyhan, Sprouse, Kaitlin R., Walls, Alexandra C., Cheng, Suna, Murphy, Mike, Pettie, Deleah, Ahlrichs, Maggie, Sydeman, Claire, Johnson, Max, Blackstone, Alyssa, Ellis, Daniel, Ravichandran, Rashmi, Fiala, Brooke, Wrenn, Samuel, Miranda, Marcos, Sliepen, Kwinten, Brouwer, Philip J.M., Antanasijevic, Aleksandar, Veesler, David, Ward, Andrew B., Kanekiyo, Masaru, Pepper, Marion, Sanders, Rogier W., and King, Neil P.
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- 2022
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4. Structure-based design of stabilized recombinant influenza neuraminidase tetramers
- Author
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Ellis, Daniel, Lederhofer, Julia, Acton, Oliver J., Tsybovsky, Yaroslav, Kephart, Sally, Yap, Christina, Gillespie, Rebecca A., Creanga, Adrian, Olshefsky, Audrey, Stephens, Tyler, Pettie, Deleah, Murphy, Michael, Sydeman, Claire, Ahlrichs, Maggie, Chan, Sidney, Borst, Andrew J., Park, Young-Jun, Lee, Kelly K., Graham, Barney S., Veesler, David, King, Neil P., and Kanekiyo, Masaru
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- 2022
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5. Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice
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Grigoryan, Lilit, Lee, Audrey, Walls, Alexandra C., Lai, Lilin, Franco, Benjamin, Arunachalam, Prabhu S., Feng, Yupeng, Luo, Wei, Vanderheiden, Abigail, Floyd, Katharine, Wrenn, Samuel, Pettie, Deleah, Miranda, Marcos C., Kepl, Elizabeth, Ravichandran, Rashmi, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, Coffman, Robert L., Novack, David, Kleanthous, Harry, O’Hagan, Derek T., van der Most, Robbert, McLellan, Jason S., Suthar, Mehul, Veesler, David, King, Neil P., and Pulendran, Bali
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- 2022
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6. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines
- Author
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Walls, Alexandra C., Miranda, Marcos C., Schäfer, Alexandra, Pham, Minh N., Greaney, Allison, Arunachalam, Prabhu S., Navarro, Mary-Jane, Tortorici, M. Alejandra, Rogers, Kenneth, O’Connor, Megan A., Shirreff, Lisa, Ferrell, Douglas E., Bowen, John, Brunette, Natalie, Kepl, Elizabeth, Zepeda, Samantha K., Starr, Tyler, Hsieh, Ching-Lin, Fiala, Brooke, Wrenn, Samuel, Pettie, Deleah, Sydeman, Claire, Sprouse, Kaitlin R., Johnson, Max, Blackstone, Alyssa, Ravichandran, Rashmi, Ogohara, Cassandra, Carter, Lauren, Tilles, Sasha W., Rappuoli, Rino, Leist, Sarah R., Martinez, David R., Clark, Matthew, Tisch, Roland, O’Hagan, Derek T., Van Der Most, Robbert, Van Voorhis, Wesley C., Corti, Davide, McLellan, Jason S., Kleanthous, Harry, Sheahan, Timothy P., Smith, Kelly D., Fuller, Deborah H., Villinger, Francois, Bloom, Jesse, Pulendran, Bali, Baric, Ralph S., King, Neil P., and Veesler, David
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- 2021
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7. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
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Arunachalam, Prabhu S., Walls, Alexandra C., Golden, Nadia, Atyeo, Caroline, Fischinger, Stephanie, Li, Chunfeng, Aye, Pyone, Navarro, Mary Jane, Lai, Lilin, Edara, Venkata Viswanadh, Roltgen, Katharina, Rogers, Kenneth, Shirreff, Lisa, Ferrell, Douglas E., Wrenn, Samuel, Pettie, Deleah, and Kraft, John C.
- Subjects
Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative.sup.1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an [alpha]-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343). Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus., Author(s): Prabhu S. Arunachalam [sup.1] , Alexandra C. Walls [sup.2] , Nadia Golden [sup.3] , Caroline Atyeo [sup.4] , Stephanie Fischinger [sup.4] , Chunfeng Li [sup.1] , Pyone Aye [sup.3] [...]
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- 2021
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8. Quadrivalent influenza nanoparticle vaccines induce broad protection
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Boyoglu-Barnum, Seyhan, Ellis, Daniel, Gillespie, Rebecca A., Hutchinson, Geoffrey B., Park, Young-Jun, Moin, Syed M., Acton, Oliver J., Ravichandran, Rashmi, Murphy, Mike, Pettie, Deleah, Matheson, Nick, Carter, Lauren, Creanga, Adrian, Watson, Michael J., Kephart, Sally, Ataca, Sila, Vaile, John R., Ueda, George, Crank, Michelle C., Stewart, Lance, Lee, Kelly K., Guttman, Miklos, Baker, David, Mascola, John R., Veesler, David, Graham, Barney S., King, Neil P., and Kanekiyo, Masaru
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- 2021
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9. Next-Generation Vaccine Development with Nanomaterials: Recent Advances, Possibilities, and Challenges.
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Shetty, Shamitha, Alvarado, Pablo Cordero, Pettie, Deleah, and Collier, Joel H.
- Abstract
Nanomaterials are becoming important tools for vaccine development owing to their tunable and adaptable nature. Unique properties of nanomaterials afford opportunities to modulate trafficking through various tissues, complement or augment adjuvant activities, and specify antigen valency and display. This versatility has enabled recent work designing nanomaterial vaccines for a broad range of diseases, including cancer, inflammatory diseases, and various infectious diseases. Recent successes of nanoparticle vaccines during the coronavirus disease 2019 (COVID-19) pandemic have fueled enthusiasm further. In this review, the most recent developments in nanovaccines for infectious disease, cancer, inflammatory diseases, allergic diseases, and nanoadjuvants are summarized. Additionally, challenges and opportunities for clinical translation of this unique class of materials are discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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10. In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19
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Phan, Isabelle Q., Subramanian, Sandhya, Kim, David, Murphy, Michael, Pettie, Deleah, Carter, Lauren, Anishchenko, Ivan, Barrett, Lynn K., Craig, Justin, Tillery, Logan, Shek, Roger, Harrington, Whitney E., Koelle, David M., Wald, Anna, Veesler, David, King, Neil, Boonyaratanakornkit, Jim, Isoherranen, Nina, Greninger, Alexander L., Jerome, Keith R., Chu, Helen, Staker, Bart, Stewart, Lance, Myler, Peter J., and Van Voorhis, Wesley C.
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- 2021
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11. Antigen spacing on protein nanoparticles influences antibody responses to vaccination
- Author
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Ellis, Daniel, primary, Dosey, Annie, additional, Boyoglu-Barnum, Seyhan, additional, Park, Young-Jun, additional, Gillespie, Rebecca, additional, Syeda, Hubza, additional, Tsybovsky, Yaroslav, additional, Murphy, Michael, additional, Pettie, Deleah, additional, Matheson, Nicholas, additional, Chan, Sidney, additional, Ueda, George, additional, Fallas, Jorge, additional, Carter, Lauren, additional, Graham, Barney, additional, Veesler, David, additional, Kanekiyo, Masaru, additional, and King, Neil P, additional
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- 2023
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12. Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak
- Author
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Dingens, Adam S., Crawford, Katharine H. D., Adler, Amanda, Steele, Sarah L., Lacombe, Kirsten, Eguia, Rachel, Amanat, Fatima, Walls, Alexandra C., Wolf, Caitlin R., Murphy, Michael, Pettie, Deleah, Carter, Lauren, Qin, Xuan, King, Neil P., Veesler, David, Krammer, Florian, Dickerson, Jane A., Chu, Helen Y., Englund, Janet A., and Bloom, Jesse D.
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- 2020
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13. Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses
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McLeod, Brandon, primary, Mabrouk, Moustafa T., additional, Miura, Kazutoyo, additional, Ravichandran, Rashmi, additional, Kephart, Sally, additional, Hailemariam, Sophia, additional, Pham, Thao P., additional, Semesi, Anthony, additional, Kucharska, Iga, additional, Kundu, Prasun, additional, Huang, Wei-Chiao, additional, Johnson, Max, additional, Blackstone, Alyssa, additional, Pettie, Deleah, additional, Murphy, Michael, additional, Kraft, John C., additional, Leaf, Elizabeth M., additional, Jiao, Yang, additional, van de Vegte-Bolmer, Marga, additional, van Gemert, Geert-Jan, additional, Ramjith, Jordache, additional, King, C. Richter, additional, MacGill, Randall S., additional, Wu, Yimin, additional, Lee, Kelly K., additional, Jore, Matthijs M., additional, King, Neil P., additional, Lovell, Jonathan F., additional, and Julien, Jean-Philippe, additional
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- 2022
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14. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
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Cagigi, Alberto, primary, Yu, Meng, additional, Österberg, Björn, additional, Svensson, Julia, additional, Falck-Jones, Sara, additional, Vangeti, Sindhu, additional, Åhlberg, Eric, additional, Azizmohammadi, Lida, additional, Warnqvist, Anna, additional, Falck-Jones, Ryan, additional, Gubisch, Pia C., additional, Ödemis, Mert, additional, Ghafoor, Farangies, additional, Eisele, Mona, additional, Lenart, Klara, additional, Bell, Max, additional, Johansson, Niclas, additional, Albert, Jan, additional, Sälde, Jörgen, additional, Pettie, Deleah D., additional, Murphy, Michael P., additional, Carter, Lauren, additional, King, Neil P., additional, Ols, Sebastian, additional, Normark, Johan, additional, Ahlm, Clas, additional, Forsell, Mattias N., additional, Färnert, Anna, additional, Loré, Karin, additional, and Smed-Sörensen, Anna, additional
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- 2021
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15. Stabilization of the SARS-CoV-2 Spike Receptor-Binding Domain Using Deep Mutational Scanning and Structure-Based Design
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Ellis, Daniel, primary, Brunette, Natalie, additional, Crawford, Katharine H. D., additional, Walls, Alexandra C., additional, Pham, Minh N., additional, Chen, Chengbo, additional, Herpoldt, Karla-Luise, additional, Fiala, Brooke, additional, Murphy, Michael, additional, Pettie, Deleah, additional, Kraft, John C., additional, Malone, Keara D., additional, Navarro, Mary Jane, additional, Ogohara, Cassandra, additional, Kepl, Elizabeth, additional, Ravichandran, Rashmi, additional, Sydeman, Claire, additional, Ahlrichs, Maggie, additional, Johnson, Max, additional, Blackstone, Alyssa, additional, Carter, Lauren, additional, Starr, Tyler N., additional, Greaney, Allison J., additional, Lee, Kelly K., additional, Veesler, David, additional, Bloom, Jesse D., additional, and King, Neil P., additional
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- 2021
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16. Structure-based design of stabilized recombinant influenza neuraminidase tetramers
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Ellis, Daniel, primary, Lederhofer, Julia, additional, Acton, Oliver J., additional, Tsybovsky, Yaroslav, additional, Kephart, Sally, additional, Yap, Christina, additional, Gillespie, Rebecca A., additional, Creanga, Adrian, additional, Stephens, Tyler, additional, Pettie, Deleah, additional, Murphy, Michael, additional, Borst, Andrew J., additional, Park, Young-Jun, additional, Lee, Kelly K., additional, Graham, Barney S., additional, Veesler, David, additional, King, Neil P., additional, and Kanekiyo, Masaru, additional
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- 2021
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17. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- Author
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Cagigi, Alberto, Yu, Meng, Österberg, Björn, Svensson, Julia, Falck-Jones, Sara, Vangeti, Sindhu, Åhlberg, Eric, Azizmohammadi, Lida, Warnqvist, Anna, Falck-Jones, Ryan, Gubisch, Pia C., Ödemis, Mert, Ghafoor, Farangies, Eisele, Mona, Lenart, Klara, Bell, Max, Johansson, Niclas, Albert, Jan, Sälde, Jörgen, Pettie, Deleah D., Murphy, Michael P., Carter, Lauren, King, Neil P., Ols, Sebastian, Normark, Johan, Ahlm, Clas, Forsell, Mattias N., Färnert, Anna, Loré, Karin, Smed-Sörensen, Anna, Cagigi, Alberto, Yu, Meng, Österberg, Björn, Svensson, Julia, Falck-Jones, Sara, Vangeti, Sindhu, Åhlberg, Eric, Azizmohammadi, Lida, Warnqvist, Anna, Falck-Jones, Ryan, Gubisch, Pia C., Ödemis, Mert, Ghafoor, Farangies, Eisele, Mona, Lenart, Klara, Bell, Max, Johansson, Niclas, Albert, Jan, Sälde, Jörgen, Pettie, Deleah D., Murphy, Michael P., Carter, Lauren, King, Neil P., Ols, Sebastian, Normark, Johan, Ahlm, Clas, Forsell, Mattias N., Färnert, Anna, Loré, Karin, and Smed-Sörensen, Anna
- Abstract
Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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- 2021
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18. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines
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Walls, Alexandra C., primary, Miranda, Marcos C., additional, Pham, Minh N., additional, Schäfer, Alexandra, additional, Greaney, Allison, additional, Arunachalam, Prabhu S., additional, Navarro, Mary-Jane, additional, Tortorici, M. Alejandra, additional, Rogers, Kenneth, additional, O’Connor, Megan A., additional, Shireff, Lisa, additional, Ferrell, Douglas E., additional, Brunette, Natalie, additional, Kepl, Elizabeth, additional, Bowen, John, additional, Zepeda, Samantha K., additional, Starr, Tyler, additional, Hsieh, Ching-Lin, additional, Fiala, Brooke, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, Sydeman, Claire, additional, Johnson, Max, additional, Blackstone, Alyssa, additional, Ravichandran, Rashmi, additional, Ogohara, Cassandra, additional, Carter, Lauren, additional, Tilles, Sasha W., additional, Rappuoli, Rino, additional, O’Hagan, Derek T., additional, Van Der Most, Robbert, additional, Van Voorhis, Wesley C., additional, McLellan, Jason S., additional, Kleanthous, Harry, additional, Sheahan, Timothy P., additional, Fuller, Deborah H., additional, Villinger, Francois, additional, Bloom, Jesse, additional, Pulendran, Bali, additional, Baric, Ralph, additional, King, Neil, additional, and Veesler, David, additional
- Published
- 2021
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19. Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates
- Author
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Arunachalam, Prabhu S., primary, Walls, Alexandra C., additional, Golden, Nadia, additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Li, Chunfeng, additional, Aye, Pyone, additional, Navarro, Mary Jane, additional, Lai, Lilin, additional, Edara, Venkata Viswanadh, additional, Röltgen, Katharina, additional, Rogers, Kenneth, additional, Shirreff, Lisa, additional, Ferrell, Douglas E, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, Kraft, John C., additional, Miranda, Marcos C., additional, Kepl, Elizabeth, additional, Sydeman, Claire, additional, Brunette, Natalie, additional, Murphy, Michael, additional, Fiala, Brooke, additional, Carter, Lauren, additional, White, Alexander G, additional, Trisal, Meera, additional, Hsieh, Ching-Lin, additional, Russell-Lodrigue, Kasi, additional, Monjure, Christopher, additional, Dufour, Jason, additional, Doyle-Meyer, Lara, additional, Bohm, Rudolph B., additional, Maness, Nicholas J., additional, Roy, Chad, additional, Plante, Jessica A., additional, Plante, Kenneth S., additional, Zhu, Alex, additional, Gorman, Matthew J., additional, Shin, Sally, additional, Shen, Xiaoying, additional, Fontenot, Jane, additional, Gupta, Shakti, additional, O’Hagan, Derek T., additional, Most, Robbert Van Der, additional, Rappuoli, Rino, additional, Coffman, Robert L., additional, Novack, David, additional, McLellan, Jason S., additional, Subramaniam, Shankar, additional, Montefiori, David, additional, Boyd, Scott D., additional, Flynn, JoAnne L., additional, Alter, Galit, additional, Villinger, Francois, additional, Kleanthous, Harry, additional, Rappaport, Jay, additional, Suthar, Mehul, additional, King, Neil P., additional, Veesler, David, additional, and Pulendran, Bali, additional
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- 2021
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20. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- Author
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Cagigi, Alberto, primary, Yu, Meng, additional, Österberg, Björn, additional, Svensson, Julia, additional, Falck-Jones, Sara, additional, Vangeti, Sindhu, additional, Åhlberg, Eric, additional, Azizmohammadi, Lida, additional, Warnqvist, Anna, additional, Falck-Jones, Ryan, additional, Gubisch, Pia C, additional, Ödemis, Mert, additional, Ghafoor, Farangies, additional, Eisele, Mona, additional, Lenart, Klara, additional, Bell, Max, additional, Johansson, Niclas, additional, Albert, Jan, additional, Sälde, Jörgen, additional, Pettie, Deleah, additional, Murphy, Michael, additional, Carter, Lauren, additional, King, Neil P, additional, Ols, Sebastian, additional, Normark, Johan, additional, Ahlm, Clas, additional, Forsell, Mattias, additional, Färnert, Anna, additional, Loré, Karin, additional, and Smed-Sörensen, Anna, additional
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- 2020
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21. Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2
- Author
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Walls, Alexandra C., primary, Fiala, Brooke, additional, Schäfer, Alexandra, additional, Wrenn, Samuel, additional, Pham, Minh N., additional, Murphy, Michael, additional, Tse, Longping V., additional, Shehata, Laila, additional, O’Connor, Megan A., additional, Chen, Chengbo, additional, Navarro, Mary Jane, additional, Miranda, Marcos C., additional, Pettie, Deleah, additional, Ravichandran, Rashmi, additional, Kraft, John C., additional, Ogohara, Cassandra, additional, Palser, Anne, additional, Chalk, Sara, additional, Lee, E-Chiang, additional, Guerriero, Kathryn, additional, Kepl, Elizabeth, additional, Chow, Cameron M., additional, Sydeman, Claire, additional, Hodge, Edgar A., additional, Brown, Brieann, additional, Fuller, Jim T., additional, Dinnon, Kenneth H., additional, Gralinski, Lisa E., additional, Leist, Sarah R., additional, Gully, Kendra L., additional, Lewis, Thomas B., additional, Guttman, Miklos, additional, Chu, Helen Y., additional, Lee, Kelly K., additional, Fuller, Deborah H., additional, Baric, Ralph S., additional, Kellam, Paul, additional, Carter, Lauren, additional, Pepper, Marion, additional, Sheahan, Timothy P., additional, Veesler, David, additional, and King, Neil P., additional
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- 2020
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22. Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection
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Crawford, Katharine H D, primary, Dingens, Adam S, additional, Eguia, Rachel, additional, Wolf, Caitlin R, additional, Wilcox, Naomi, additional, Logue, Jennifer K, additional, Shuey, Kiel, additional, Casto, Amanda M, additional, Fiala, Brooke, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, King, Neil P, additional, Greninger, Alexander L, additional, Chu, Helen Y, additional, and Bloom, Jesse D, additional
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- 2020
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23. Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection
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Crawford, Katharine H.D., primary, Dingens, Adam S., additional, Eguia, Rachel, additional, Wolf, Caitlin R., additional, Wilcox, Naomi, additional, Logue, Jennifer K., additional, Shuey, Kiel, additional, Casto, Amanda M., additional, Fiala, Brooke, additional, Wrenn, Samuel, additional, Pettie, Deleah, additional, King, Neil P., additional, Chu, Helen Y., additional, and Bloom, Jesse D., additional
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- 2020
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24. Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines
- Author
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Boyoglu-Barnum, Seyhan, primary, Ellis, Daniel, additional, Gillespie, Rebecca A., additional, Hutchinson, Geoffrey B., additional, Park, Young-Jun, additional, Moin, Syed M., additional, Acton, Oliver, additional, Ravichandran, Rashmi, additional, Murphy, Mike, additional, Pettie, Deleah, additional, Matheson, Nick, additional, Carter, Lauren, additional, Creanga, Adrian, additional, Watson, Michael J., additional, Kephart, Sally, additional, Vaile, John R., additional, Ueda, George, additional, Crank, Michelle C., additional, Stewart, Lance, additional, Lee, Kelly K., additional, Guttman, Miklos, additional, Baker, David, additional, Mascola, John R., additional, Veesler, David, additional, Graham, Barney S., additional, King, Neil P., additional, and Kanekiyo, Masaru, additional
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- 2020
- Full Text
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25. Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak
- Author
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Dingens, Adam S., primary, Crawford, Katharine H. D., additional, Adler, Amanda, additional, Steele, Sarah L., additional, Lacombe, Kirsten, additional, Eguia, Rachel, additional, Amanat, Fatima, additional, Walls, Alexandra C., additional, Wolf, Caitlin R., additional, Murphy, Michael, additional, Pettie, Deleah, additional, Carter, Lauren, additional, Qin, Xuan, additional, King, Neil P., additional, Veesler, David, additional, Krammer, Florian, additional, Dickerson, Jane A., additional, Chu, Helen Y., additional, Englund, Janet A., additional, and Bloom, Jesse D., additional
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- 2020
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26. Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays
- Author
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Crawford, Katharine H. D., primary, Eguia, Rachel, additional, Dingens, Adam S., additional, Loes, Andrea N., additional, Malone, Keara D., additional, Wolf, Caitlin R., additional, Chu, Helen Y., additional, Tortorici, M. Alejandra, additional, Veesler, David, additional, Murphy, Michael, additional, Pettie, Deleah, additional, King, Neil P., additional, Balazs, Alejandro B., additional, and Bloom, Jesse D., additional
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- 2020
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27. Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 Spike protein for neutralization assays
- Author
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Crawford, Katharine H.D., primary, Eguia, Rachel, additional, Dingens, Adam S., additional, Loes, Andrea N., additional, Malone, Keara D., additional, Wolf, Caitlin R., additional, Chu, Helen Y., additional, Tortorici, M. Alejandra, additional, Veesler, David, additional, Murphy, Michael, additional, Pettie, Deleah, additional, King, Neil P., additional, Balazs, Alejandro B., additional, and Bloom, Jesse D., additional
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- 2020
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28. Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
- Author
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Crawford, Katharine H D, Dingens, Adam S, Eguia, Rachel, Wolf, Caitlin R, Wilcox, Naomi, Logue, Jennifer K, Shuey, Kiel, Casto, Amanda M, Fiala, Brooke, Wrenn, Samuel, Pettie, Deleah, King, Neil P, Greninger, Alexander L, Chu, Helen Y, and Bloom, Jesse D
- Subjects
COVID-19 ,ANTIBODY titer ,VIRAL proteins ,VIRUS diseases ,PROTEIN domains - Abstract
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30-152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2. [ABSTRACT FROM AUTHOR]
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- 2021
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29. Antigen spacing on protein nanoparticles influences antibody responses to vaccination.
- Author
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Ellis D, Dosey A, Boyoglu-Barnum S, Park YJ, Gillespie R, Syeda H, Tsybovsky Y, Murphy M, Pettie D, Matheson N, Chan S, Ueda G, Fallas JA, Carter L, Graham BS, Veesler D, Kanekiyo M, and King NP
- Abstract
Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship between immunogen structure and immunogenicity is limited. Here we use computational protein design to generate a self-assembling nanoparticle vaccine platform based on the head domain of influenza hemagglutinin (HA) that enables precise control of antigen conformation, flexibility, and spacing on the nanoparticle exterior. Domain-based HA head antigens were presented either as monomers or in a native-like closed trimeric conformation that prevents exposure of trimer interface epitopes. These antigens were connected to the underlying nanoparticle by a rigid linker that was modularly extended to precisely control antigen spacing. We found that nanoparticle immunogens with decreased spacing between closed trimeric head antigens elicited antibodies with improved hemagglutination inhibition (HAI) and neutralization potency as well as binding breadth across diverse HAs within a subtype. Our "trihead" nanoparticle immunogen platform thus enables new insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used to generate next-generation vaccines against influenza and other viruses., Competing Interests: Declaration of Interests N.P.K. is a cofounder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. The King lab has received unrelated sponsored research agreements from Pfizer and GSK. D.E. is a shareholder of Icosavax, Inc. A.D., D.E., M.K., and N.P.K. are listed as co-inventors on patent applications filed by the University of Washington related to this work. All other authors declare no competing interests related to this work.
- Published
- 2023
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30. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
- Author
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Walls AC, Miranda MC, Pham MN, Schäfer A, Greaney A, Arunachalam PS, Navarro MJ, Tortorici MA, Rogers K, O'Connor MA, Shireff L, Ferrell DE, Brunette N, Kepl E, Bowen J, Zepeda SK, Starr T, Hsieh CL, Fiala B, Wrenn S, Pettie D, Sydeman C, Johnson M, Blackstone A, Ravichandran R, Ogohara C, Carter L, Tilles SW, Rappuoli R, O'Hagan DT, Van Der Most R, Van Voorhis WC, McLellan JS, Kleanthous H, Sheahan TP, Fuller DH, Villinger F, Bloom J, Pulendran B, Baric R, King N, and Veesler D
- Abstract
Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic., Competing Interests: Declaration of interest A.C.W, N.P.K. and D.V., are named as inventors on patent applications filed by the University of Washington based on the studies presented in this paper. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. D.V. is a consultant for and has received an unrelated sponsored research agreement from Vir Biotechnology Inc. R.R., D.T.O., and R.V.D.M are employees of GlaxoSmithKline. C.-L.H. and J.S.M. are inventors on U.S. patent application no. 63/032,502 “Engineered Coronavirus Spike (S) Protein and Methods of Use Thereof. The other authors declare no competing interests.
- Published
- 2021
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31. Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.
- Author
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S Arunachalam P, Walls AC, Golden N, Atyeo C, Fischinger S, Li C, Aye P, Navarro MJ, Lai L, Edara VV, Roltgen K, Rogers K, Shirreff L, Ferrell DE, Wrenn S, Pettie D, Kraft JC, Miranda MC, Kepl E, Sydeman C, Brunette N, Murphy M, Fiala B, Carter L, White AG, Trisal M, Hsieh CL, Russell-Lodrigue K, Monjure C, Dufour J, Doyle-Meyer L, Bohm RB, Maness NJ, Roy C, Plante JA, Plante KS, Zhu A, Gorman MJ, Shin S, Shen X, Fontenot J, Gupta S, O Hagan DT, Most RV, Rappuoli R, Coffman RL, Novack D, McLellan JS, Subramaniam S, Montefiori D, Boyd SD, Flynn JL, Alter G, Villinger F, Kleanthous H, Rappaport J, Suthar M, King NP, Veesler D, and Pulendran B
- Abstract
The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.
- Published
- 2021
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32. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.
- Author
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Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, Tse LV, Shehata L, O'Connor MA, Chen C, Navarro MJ, Miranda MC, Pettie D, Ravichandran R, Kraft JC, Ogohara C, Palser A, Chalk S, Lee EC, Kepl E, Chow CM, Sydeman C, Hodge EA, Brown B, Fuller JT, Dinnon KH 3rd, Gralinski LE, Leist SR, Gully KL, Lewis TB, Guttman M, Chu HY, Lee KK, Fuller DH, Baric RS, Kellam P, Carter L, Pepper M, Sheahan TP, Veesler D, and King NP
- Abstract
A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic., Competing Interests: DECLARATION OF INTERESTS A.C.W, D.V., and N.P.K. are named as inventors on patent applications filed by the University of Washington based on the studies presented in this paper. N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. H.Y.C. is a consultant for Merck and Pfizer, and has received research funding from Sanofi-Pasteur, Roche-Genentech, Cepheid, and Ellume outside of the submitted work. P.K., A.P., and S.C. are employees and shareholders of Kymab Ltd. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. The other authors declare no competing interests.
- Published
- 2020
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33. Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak.
- Author
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Dingens AS, Crawford KHD, Adler A, Steele SL, Lacombe K, Eguia R, Amanat F, Walls AC, Wolf CR, Murphy M, Pettie D, Carter L, Qin X, King NP, Veesler D, Krammer F, Dickerson JA, Chu HY, Englund JA, and Bloom JD
- Abstract
Children are strikingly underrepresented in COVID-19 case counts
1-3 . In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases1 . One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults1,4-7 . To better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screened 1,775 residual samples from Seattle Children's Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈ 1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children had neutralizing activity, including one that neutralized at a dilution >1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests., Competing Interests: Competing interests H.Y.C. is a consultant for Merck and Glaxo Smith Kline and receives research funding from Sanofi Pasteur, outside of the submitted work. N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. Mount Sinai has licensed serological assays to commercial entities and has filed for patent protection for serological assays. J.A.E. is a consultant for Sanofi Pasteur and Meissa Vaccines. The other authors declare no conflicts of interest.- Published
- 2020
- Full Text
- View/download PDF
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