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1. Clinical and Genomic Epidemiology of Coxsackievirus A21 and Enterovirus D68 in Homeless Shelters, King County, Washington, USA, 2019-2021. (SYNOPSIS)

Author

Cox, Sarah N., Casto, Amanda M., Franko, Nicholas M., Chow, Eric J., Han, Peter D., Gamboa, Luis, Pfau, Brian, Xie, Hong, Kong, Kevin, Sereewit, Jaydee, Rolfes, Melissa A., Mosites, Emily, Uyeki, Timothy M., Greninger, Alexander L., Carone, Marco, Shim, M. Mia, Bedford, Trevor, Shendure, Jay, Boeckh, Michael, Englund, Janet A., Starita, Lea M., Roychoudhury, Pavitra, and Chu, Helen Y.

Subjects
United States. Centers for Disease Control and Prevention, Nucleotide sequencing, Coxsackievirus infections, Epidemics, Communicable diseases, Genomics, DNA sequencing, Genomes, Adults, Epidemiology, Homeless shelters, Health
Abstract

Enteroviruses are responsible for [approximately equal to] 10-15 million symptomatic illnesses in the United States annually; however, epidemiologic surveillance and genetic characterization of many enterovirus subspecies is limited (1-3). Coxsackievirus [...]

Published
2024
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2. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

Author

Cameroni, Elisabetta, Bowen, John E., Rosen, Laura E., Saliba, Christian, Zepeda, Samantha K., Culap, Katja, Pinto, Dora, VanBlargan, Laura A., De Marco, Anna, di Iulio, Julia, Zatta, Fabrizia, Kaiser, Hannah, Noack, Julia, Farhat, Nisar, Czudnochowski, Nadine, Havenar-Daughton, Colin, Sprouse, Kaitlin R., Dillen, Josh R., Powell, Abigail E., Chen, Alex, Maher, Cyrus, Yin, Li, Sun, David, Soriaga, Leah, Bassi, Jessica, Silacci-Fregni, Chiara, Gustafsson, Claes, Franko, Nicholas M., Logue, Jenni, Iqbal, Najeeha Talat, Mazzitelli, Ignacio, Geffner, Jorge, Grifantini, Renata, Chu, Helen, Gori, Andrea, Riva, Agostino, Giannini, Olivier, Ceschi, Alessandro, Ferrari, Paolo, Cippà, Pietro E., Franzetti-Pellanda, Alessandra, Garzoni, Christian, Halfmann, Peter J., Kawaoka, Yoshihiro, Hebner, Christy, Purcell, Lisa A., Piccoli, Luca, Pizzuto, Matteo Samuele, Walls, Alexandra C., Diamond, Michael S., Telenti, Amalio, Virgin, Herbert W., Lanzavecchia, Antonio, Snell, Gyorgy, Veesler, David, and Corti, Davide

Published
2022
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3. Cytotoxic T cells targeting spike glycoprotein are associated with hybrid immunity to SARS-CoV-2

Author

Phan, Jolie M, primary, Layton, Erik D., additional, Yu, Krystle K.Q., additional, Aguilar, Melissa S., additional, Golez, Inah, additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Rodda, Lauren B., additional, Howard, Christian A., additional, Pepper, Marion, additional, Gale, Michael, additional, Chu, Helen Y., additional, and Seshadri, Chetan, additional

Published
2023
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4. Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron

Author

Hao, Linhui, primary, Hsiang, Tien-Ying, additional, Dalmat, Ronit R., additional, Ireton, Renee, additional, Morton, Jennifer F., additional, Stokes, Caleb, additional, Netland, Jason, additional, Hale, Malika, additional, Thouvenel, Chris, additional, Wald, Anna, additional, Franko, Nicholas M., additional, Huden, Kristen, additional, Chu, Helen Y., additional, Sigal, Alex, additional, Greninger, Alex L., additional, Tilles, Sasha, additional, Barrett, Lynn K., additional, Van Voorhis, Wesley C., additional, Munt, Jennifer, additional, Scobey, Trevor, additional, Baric, Ralph S., additional, Rawlings, David J., additional, Pepper, Marion, additional, Drain, Paul K., additional, and Gale, Michael, additional

Published
2023
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5. SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines

Author

Bowen, John E., primary, Park, Young-Jun, additional, Stewart, Cameron, additional, Brown, Jack T., additional, Sharkey, William K., additional, Walls, Alexandra C., additional, Joshi, Anshu, additional, Sprouse, Kaitlin R., additional, McCallum, Matthew, additional, Tortorici, M. Alejandra, additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Mazzitelli, Ignacio G., additional, Nguyen, Annalee W., additional, Silva, Rui P., additional, Huang, Yimin, additional, Low, Jun Siong, additional, Jerak, Josipa, additional, Tiles, Sasha W., additional, Ahmed, Kumail, additional, Shariq, Asefa, additional, Dan, Jennifer M., additional, Zhang, Zeli, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Snell, Gyorgy, additional, Posavad, Christine M., additional, Iqbal, Najeeha Talat, additional, Geffner, Jorge, additional, Bandera, Alessandra, additional, Gori, Andrea, additional, Sallusto, Federica, additional, Maynard, Jennifer A., additional, Crotty, Shane, additional, Van Voorhis, Wesley C., additional, Simmerling, Carlos, additional, Grifantini, Renata, additional, Chu, Helen Y., additional, Corti, Davide, additional, and Veesler, David, additional

Published
2022
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7. 1456. Environmental and Nasal Pathogen Surveillance in Seattle Area Homeless Shelters

Author

Franko, Nicholas M, primary, Rogers, Julia H, additional, Chow, Eric J, additional, Huden, Kristen, additional, Link, Amy C, additional, Han, Peter D, additional, Wolf, Caitlin R, additional, Logue, Jennifer, additional, McDonald, Dylan, additional, Shim, Mi-Hyun M, additional, Hughes, James, additional, Shendure, Jay, additional, Boeckh, Michael J, additional, Englund, Janet A, additional, Starita, Lea, additional, and Chu, Helen Y, additional

Published
2022
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9. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author

Park, Young-Jun, primary, Pinto, Dora, additional, Walls, Alexandra C., additional, Liu, Zhuoming, additional, De Marco, Anna, additional, Benigni, Fabio, additional, Zatta, Fabrizia, additional, Silacci-Fregni, Chiara, additional, Bassi, Jessica, additional, Sprouse, Kaitlin R., additional, Addetia, Amin, additional, Bowen, John E., additional, Stewart, Cameron, additional, Giurdanella, Martina, additional, Saliba, Christian, additional, Guarino, Barbara, additional, Schmid, Michael A., additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Dang, Ha V., additional, Hauser, Kevin, additional, di Iulio, Julia, additional, Rivera, William, additional, Schnell, Gretja, additional, Rajesh, Anushka, additional, Zhou, Jiayi, additional, Farhat, Nisar, additional, Kaiser, Hannah, additional, Montiel-Ruiz, Martin, additional, Noack, Julia, additional, Lempp, Florian A., additional, Janer, Javier, additional, Abdelnabi, Rana, additional, Maes, Piet, additional, Ferrari, Paolo, additional, Ceschi, Alessandro, additional, Giannini, Olivier, additional, de Melo, Guilherme Dias, additional, Kergoat, Lauriane, additional, Bourhy, Hervé, additional, Neyts, Johan, additional, Soriaga, Leah, additional, Purcell, Lisa A., additional, Snell, Gyorgy, additional, Whelan, Sean P. J., additional, Lanzavecchia, Antonio, additional, Virgin, Herbert W., additional, Piccoli, Luca, additional, Chu, Helen Y., additional, Pizzuto, Matteo Samuele, additional, Corti, Davide, additional, and Veesler, David, additional

Published
2022
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10. Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2

Author

Farrell, Ariana Ghez, primary, Dadonaite, Bernadeta, additional, Greaney, Allison J., additional, Eguia, Rachel, additional, Loes, Andrea N., additional, Franko, Nicholas M., additional, Logue, Jennifer, additional, Carreño, Juan Manuel, additional, Abbad, Anass, additional, Chu, Helen Y., additional, Matreyek, Kenneth A., additional, and Bloom, Jesse D., additional

Published
2022
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11. Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines

Author

Bowen, John E., primary, Addetia, Amin, additional, Dang, Ha V., additional, Stewart, Cameron, additional, Brown, Jack T., additional, Sharkey, William K., additional, Sprouse, Kaitlin R., additional, Walls, Alexandra C., additional, Mazzitelli, Ignacio G., additional, Logue, Jennifer K., additional, Franko, Nicholas M., additional, Czudnochowski, Nadine, additional, Powell, Abigail E., additional, Dellota, Exequiel, additional, Ahmed, Kumail, additional, Ansari, Asefa Shariq, additional, Cameroni, Elisabetta, additional, Gori, Andrea, additional, Bandera, Alessandra, additional, Posavad, Christine M., additional, Dan, Jennifer M., additional, Zhang, Zeli, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Crotty, Shane, additional, Iqbal, Najeeha Talat, additional, Corti, Davide, additional, Geffner, Jorge, additional, Snell, Gyorgy, additional, Grifantini, Renata, additional, Chu, Helen Y., additional, and Veesler, David, additional

Published
2022
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12. Dynamics of SARS-CoV-2 VOC neutralization and novel mAb reveal protection against Omicron

Author

Hao, Linhui, primary, Hsiang, Tien-Ying, additional, Dalmat, Ronit R., additional, Ireton, Renee, additional, Morton, Jennifer, additional, Stokes, Caleb, additional, Netland, Jason, additional, Hale, Malika, additional, Thouvenel, Chris, additional, Wald, Anna, additional, Franko, Nicholas M, additional, Huden, Kristen, additional, Chu, Helen, additional, Greninger, Alex, additional, Tilles, Sasha, additional, Barrett, Lynn K., additional, Van Voorhis, Wesley C., additional, Munt, Jennifer, additional, Scobey, Trevor, additional, Baric, Ralph S., additional, Rawlings, David, additional, Pepper, Marion, additional, Drain, Paul K., additional, and Gale, Michael, additional

Published
2022
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13. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author

Park, Young-Jun, Pinto, Dora, Walls, Alexandra C, Liu, Zhuoming, De Marco, Anna, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R, Addetia, Amin, Bowen, John E, Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A, Franko, Nicholas M, Logue, Jennifer K, Dang, Ha V, Hauser, Kevin, di Iulio, Julia, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi, Farhat, Nisar, Kaiser, Hannah, Montiel-Ruiz, Martin, Noack, Julia, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, De Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, Corti, Davide; https://orcid.org/0000-0002-5797-1364, Park, Young-Jun, Pinto, Dora, Walls, Alexandra C, Liu, Zhuoming, De Marco, Anna, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R, Addetia, Amin, Bowen, John E, Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A, Franko, Nicholas M, Logue, Jennifer K, Dang, Ha V, Hauser, Kevin, di Iulio, Julia, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi, Farhat, Nisar, Kaiser, Hannah, Montiel-Ruiz, Martin, Noack, Julia, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, De Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, and Corti, Davide; https://orcid.org/0000-0002-5797-1364

Abstract

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

Published
2022

14. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author

Park, Young-Jun; https://orcid.org/0000-0003-2901-6949, Pinto, Dora, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Liu, Zhuoming; https://orcid.org/0000-0001-8198-0976, De Marco, Anna; https://orcid.org/0000-0001-9641-4838, Benigni, Fabio; https://orcid.org/0000-0002-1974-5606, Zatta, Fabrizia; https://orcid.org/0000-0003-4945-8058, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Sprouse, Kaitlin R; https://orcid.org/0000-0003-0007-2226, Addetia, Amin; https://orcid.org/0000-0001-6703-3841, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Stewart, Cameron; https://orcid.org/0000-0002-2786-6256, Giurdanella, Martina, Saliba, Christian; https://orcid.org/0000-0003-0100-6976, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Schmid, Michael A; https://orcid.org/0000-0002-1137-9322, Franko, Nicholas M; https://orcid.org/0000-0001-8165-6332, Logue, Jennifer K; https://orcid.org/0000-0002-7889-8960, Dang, Ha V; https://orcid.org/0000-0003-1173-9241, Hauser, Kevin, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi; https://orcid.org/0000-0002-4231-3422, Farhat, Nisar; https://orcid.org/0000-0003-0905-7479, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Montiel-Ruiz, Martin; https://orcid.org/0000-0001-6200-9578, Noack, Julia; https://orcid.org/0000-0002-9113-8181, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, de Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, Corti, Davide; https://orcid.org/0000-0002-5797-1364, Park, Young-Jun; https://orcid.org/0000-0003-2901-6949, Pinto, Dora, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Liu, Zhuoming; https://orcid.org/0000-0001-8198-0976, De Marco, Anna; https://orcid.org/0000-0001-9641-4838, Benigni, Fabio; https://orcid.org/0000-0002-1974-5606, Zatta, Fabrizia; https://orcid.org/0000-0003-4945-8058, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Sprouse, Kaitlin R; https://orcid.org/0000-0003-0007-2226, Addetia, Amin; https://orcid.org/0000-0001-6703-3841, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Stewart, Cameron; https://orcid.org/0000-0002-2786-6256, Giurdanella, Martina, Saliba, Christian; https://orcid.org/0000-0003-0100-6976, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Schmid, Michael A; https://orcid.org/0000-0002-1137-9322, Franko, Nicholas M; https://orcid.org/0000-0001-8165-6332, Logue, Jennifer K; https://orcid.org/0000-0002-7889-8960, Dang, Ha V; https://orcid.org/0000-0003-1173-9241, Hauser, Kevin, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi; https://orcid.org/0000-0002-4231-3422, Farhat, Nisar; https://orcid.org/0000-0003-0905-7479, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Montiel-Ruiz, Martin; https://orcid.org/0000-0001-6200-9578, Noack, Julia; https://orcid.org/0000-0002-9113-8181, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, de Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, and Corti, Davide; https://orcid.org/0000-0002-5797-1364

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development.

Published
2022

15. Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

Author

Bowen, John E., primary, Sprouse, Kaitlin R., additional, Walls, Alexandra C., additional, Mazzitelli, Ignacio G., additional, Logue, Jennifer K., additional, Franko, Nicholas M., additional, Ahmed, Kumail, additional, Shariq, Asefa, additional, Cameroni, Elisabetta, additional, Gori, Andrea, additional, Bandera, Alessandra, additional, Posavad, Christine M., additional, Dan, Jennifer M., additional, Zhang, Zeli, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Crotty, Shane, additional, Iqbal, Najeeha Talat, additional, Corti, Davide, additional, Geffner, Jorge, additional, Grifantini, Renata, additional, Chu, Helen Y., additional, and Veesler, David, additional

Published
2022
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16. Imprinted SARS-CoV-2-Specific Memory Lymphocytes Define Hybrid Immunity

Author

Rodda, Lauren B., primary, Morawski, Peter A., additional, Pruner, Kurt B., additional, Fahning, Mitchell L., additional, Howard, Christian A., additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Eggenberger, Julie, additional, Stokes, Caleb, additional, Golez, Inah, additional, Hale, Malika, additional, Gale Jr., Michael, additional, Chu, Helen Y., additional, Campbell, Daniel J., additional, and Pepper, Marion, additional

Published
2022
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17. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

Author

Cameroni, Elisabetta, primary, Bowen, John E., additional, Rosen, Laura E., additional, Saliba, Christian, additional, Zepeda, Samantha K., additional, Culap, Katja, additional, Pinto, Dora, additional, VanBlargan, Laura A., additional, De Marco, Anna, additional, di Iulio, Julia, additional, Zatta, Fabrizia, additional, Kaiser, Hannah, additional, Noack, Julia, additional, Farhat, Nisar, additional, Czudnochowski, Nadine, additional, Havenar-Daughton, Colin, additional, Sprouse, Kaitlin R., additional, Dillen, Josh R., additional, Powell, Abigail E., additional, Chen, Alex, additional, Maher, Cyrus, additional, Yin, Li, additional, Sun, David, additional, Soriaga, Leah, additional, Bassi, Jessica, additional, Silacci-Fregni, Chiara, additional, Gustafsson, Claes, additional, Franko, Nicholas M., additional, Logue, Jenni, additional, Iqbal, Najeeha Talat, additional, Mazzitelli, Ignacio, additional, Geffner, Jorge, additional, Grifantini, Renata, additional, Chu, Helen, additional, Gori, Andrea, additional, Riva, Agostino, additional, Giannini, Olivier, additional, Ceschi, Alessandro, additional, Ferrari, Paolo, additional, Cippà, Pietro E., additional, Franzetti-Pellanda, Alessandra, additional, Garzoni, Christian, additional, Halfmann, Peter J., additional, Kawaoka, Yoshihiro, additional, Hebner, Christy, additional, Purcell, Lisa A., additional, Piccoli, Luca, additional, Pizzuto, Matteo Samuele, additional, Walls, Alexandra C., additional, Diamond, Michael S., additional, Telenti, Amalio, additional, Virgin, Herbert W., additional, Lanzavecchia, Antonio, additional, Snell, Gyorgy, additional, Veesler, David, additional, and Corti, Davide, additional

Published
2021
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18. SARS-CoV-2 spike conformation determines plasma neutralizing activity

Author

Bowen, John E., primary, Walls, Alexandra C., additional, Joshi, Anshu, additional, Sprouse, Kaitlin R., additional, Stewart, Cameron, additional, Tortorici, M. Alejandra, additional, Franko, Nicholas M., additional, Logue, Jennifer K., additional, Mazzitelli, Ignacio G., additional, Tiles, Sasha W, additional, Ahmed, Kumail, additional, Shariq, Asefa, additional, Snell, Gyorgy, additional, Iqbal, Najeeha Talat, additional, Geffner, Jorge, additional, Bandera, Alessandra, additional, Gori, Andrea, additional, Grifantini, Renata, additional, Chu, Helen Y., additional, Van Voorhis, Wesley C., additional, Corti, Davide, additional, and Veesler, David, additional

Published
2021
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20. A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections

Author

Vick, Sarah C., primary, Frutoso, Marie, additional, Mair, Florian, additional, Konecny, Andrew J., additional, Greene, Evan, additional, Wolf, Caitlin R., additional, Logue, Jennifer K., additional, Franko, Nicholas M., additional, Boonyaratanakornkit, Jim, additional, Gottardo, Raphael, additional, Schiffer, Joshua T., additional, Chu, Helen Y., additional, Prlic, Martin, additional, and Lund, Jennifer M., additional

Published
2021
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21. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages.

Author

Young-Jun Park, Pinto, Dora, Walls, Alexandra C., Zhuoming Liu, De Marco, Anna, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R., Addetia, Amin, Bowen, John E., Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A., Franko, Nicholas M., Logue, Jennifer K., and Dang, Ha V.

Published
2022
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23. Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2.

Author

Farrell AG, Dadonaite B, Greaney AJ, Eguia R, Loes AN, Franko NM, Logue J, Carreño JM, Abbad A, Chu HY, Matreyek KA, and Bloom JD

Abstract

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on details of the experimental assay. Here we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. But for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.

Published
2022
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24. Dynamics of SARS-CoV-2 VOC neutralization and novel mAb reveal protection against Omicron.

Author

Hao L, Hsiang TY, Dalmat RR, Ireton R, Morton J, Stokes C, Netland J, Hale M, Thouvenel C, Wald A, Franko NM, Huden K, Chu H, Greninger A, Tilles S, Barrett LK, Van Voorhis WC, Munt J, Scobey T, Baric RS, Rawlings D, Pepper M, Drain PK, and Gale M

Abstract

To evaluate SARS-CoV-2 variants we isolated SARS-CoV-2 temporally during the pandemic starting with first appearance of virus in the Western hemisphere near Seattle, WA, USA, and isolated each known major variant class, revealing the dynamics of emergence and complete take-over of all new cases by current Omicron variants. We assessed virus neutralization in a first-ever full comparison across variants and evaluated a novel monoclonal antibody (Mab). We found that convalescence greater than 5-months provides little-to-no protection against SARS-CoV-2 variants, vaccination enhances immunity against variants with the exception of Omicron BA.1, and paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a 2-dose regimen. We also reveal a novel Mab that effectively neutralizes Omicron BA.1 and BA.2 variants over clinically-approved Mabs. Our observations underscore the need for continued vaccination efforts, with innovation for vaccine and Mab improvement, for protection against variants of SARS-CoV-2., Summary: We isolated SARS-CoV-2 temporally starting with emergence of virus in the Western hemisphere. Neutralization analyses across all variant lineages show that vaccine-boost regimen provides protection against Omicron BA.1. We reveal a Mab that protects against Omicron BA.1 and BA.2 variants.

Published
2022
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25. Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines.

Author

Bowen JE, Sprouse KR, Walls AC, Mazzitelli IG, Logue JK, Franko NM, Ahmed K, Shariq A, Cameroni E, Gori A, Bandera A, Posavad CM, Dan JM, Zhang Z, Weiskopf D, Sette A, Crotty S, Iqbal NT, Corti D, Geffner J, Grifantini R, Chu HY, and Veesler D

Abstract

The SARS-CoV-2 Omicron variant of concern comprises three sublineages designated BA.1, BA.2, and BA.3, with BA.2 steadily replacing the globally dominant BA.1. We show that the large number of BA.1 and BA.2 spike mutations severely dampen plasma neutralizing activity elicited by infection or seven clinical vaccines, with cross-neutralization of BA.2 being consistently more potent than that of BA.1, independent of the vaccine platform and number of doses. Although mRNA vaccines induced the greatest magnitude of Omicron BA.1 and BA.2 plasma neutralizing activity, administration of a booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1 and BA.2 across all vaccines evaluated. Our data suggest that although BA.1 and BA.2 evade polyclonal neutralizing antibody responses, current vaccine boosting regimens may provide sufficient protection against Omicron-induced disease.

Published
2022
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26. SARS-CoV-2 spike conformation determines plasma neutralizing activity.

Author

Bowen JE, Walls AC, Joshi A, Sprouse KR, Stewart C, Tortorici MA, Franko NM, Logue JK, Mazzitelli IG, Tiles SW, Ahmed K, Shariq A, Snell G, Iqbal NT, Geffner J, Bandera A, Gori A, Grifantini R, Chu HY, Van Voorhis WC, Corti D, and Veesler D

Abstract

Numerous safe and effective COVID-19 vaccines have been developed that utilize various delivery technologies and engineering strategies. The influence of the SARS-CoV-2 spike (S) glycoprotein conformation on antibody responses induced by vaccination or infection in humans remains unknown. To address this question, we compared plasma antibodies elicited by six globally-distributed vaccines or infection and observed markedly higher binding titers for vaccines encoding a prefusion-stabilized S relative to other groups. Prefusion S binding titers positively correlated with plasma neutralizing activity, indicating that physical stabilization of the prefusion conformation enhances protection against SARS-CoV-2. We show that almost all plasma neutralizing activity is directed to prefusion S, in particular the S 1 subunit, and that variant cross-neutralization is mediated solely by RBD-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants and longer durability than current technologies.

Published
2021
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27. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.

Author

Cameroni E, Saliba C, Bowen JE, Rosen LE, Culap K, Pinto D, VanBlargan LA, De Marco A, Zepeda SK, Iulio JD, Zatta F, Kaiser H, Noack J, Farhat N, Czudnochowski N, Havenar-Daughton C, Sprouse KR, Dillen JR, Powell AE, Chen A, Maher C, Yin L, Sun D, Soriaga L, Bassi J, Silacci-Fregni C, Gustafsson C, Franko NM, Logue J, Iqbal NT, Mazzitelli I, Geffner J, Grifantini R, Chu H, Gori A, Riva A, Giannini O, Ceschi A, Ferrari P, Cippà P, Franzetti-Pellanda A, Garzoni C, Halfmann PJ, Kawaoka Y, Hebner C, Purcell LA, Piccoli L, Pizzuto MS, Walls AC, Diamond MS, Telenti A, Virgin HW, Lanzavecchia A, Veesler D, Snell G, and Corti D

Abstract

The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb 1 , retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab 2 , S2X259 3 and S2H97 4 , neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

Published
2021
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