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1. Influenza vaccination stimulates maturation of the human T follicular helper cell response

Author

Schattgen, Stefan A., Turner, Jackson S., Ghonim, Mohamed A., Crawford, Jeremy Chase, Schmitz, Aaron J., Kim, Hyunjin, Zhou, Julian Q., Awad, Walid, Mettelman, Robert C., Kim, Wooseob, McIntire, Katherine M., Haile, Alem, Klebert, Michael K., Suessen, Teresa, Middleton, William D., Teefey, Sharlene A., Presti, Rachel M., Ellebedy, Ali H., and Thomas, Paul G.

Published
2024
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2. CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

Author

Borcherding, Nicholas, Kim, Wooseob, Quinn, Michael, Han, Fangjie, Zhou, Julian Q., Sturtz, Alexandria J., Schmitz, Aaron J., Lei, Tingting, Schattgen, Stefan A., Klebert, Michael K., Suessen, Teresa, Middleton, William D., Goss, Charles W., Liu, Chang, Crawford, Jeremy Chase, Thomas, Paul G., Teefey, Sharlene A., Presti, Rachel M., O’Halloran, Jane A., Turner, Jackson S., Ellebedy, Ali H., and Mudd, Philip A.

Published
2024
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3. SARS-CoV-2 Omicron boosting induces de novo B cell response in humans

Author

Alsoussi, Wafaa B., Malladi, Sameer Kumar, Zhou, Julian Q., Liu, Zhuoming, Ying, Baoling, Kim, Wooseob, Schmitz, Aaron J., Lei, Tingting, Horvath, Stephen C., Sturtz, Alexandria J., McIntire, Katherine M., Evavold, Birk, Han, Fangjie, Scheaffer, Suzanne M., Fox, Isabella F., Mirza, Senaa F., Parra-Rodriguez, Luis, Nachbagauer, Raffael, Nestorova, Biliana, Chalkias, Spyros, Farnsworth, Christopher W., Klebert, Michael K., Pusic, Iskra, Strnad, Benjamin S., Middleton, William D., Teefey, Sharlene A., Whelan, Sean P. J., Diamond, Michael S., Paris, Robert, O’Halloran, Jane A., Presti, Rachel M., Turner, Jackson S., and Ellebedy, Ali H.

Published
2023
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5. Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

Author

Hansen, Lena, McMahon, Meagan, Turner, Hannah L., Zhu, Xueyong, Turner, Jackson S., Ozorowski, Gabriel, Stadlbauer, Daniel, Vahokoski, Juha, Schmitz, Aaron J., Rizk, Amena A., Alsoussi, Wafaa B., Strohmeier, Shirin, Yu, Wenli, Choreño-Parra, José Alberto, Jiménez-Alvarez, Luis, Cruz-Lagunas, Alfredo, Zúñiga, Joaquín, Mudd, Philip A., Cox, Rebecca J., Wilson, Ian A., Ward, Andrew B., Ellebedy, Ali H., and Krammer, Florian

Published
2023
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6. Distinct Inflammatory Profiles Distinguish COVID-19 from Influenza with Limited Contributions from Cytokine Storm

Author

Mudd, Philip A., primary, Crawford, Jeremy Chase, additional, Turner, Jackson S., additional, Souquette, Aisha, additional, Reynolds, Daniel, additional, Bender, Diane, additional, Bosanquet, James P., additional, Anand, Nitin J., additional, Striker, David A., additional, Martin, R. Scott, additional, Boon, Adrianus C. M., additional, House, Stacey L., additional, Remy, Kenneth E., additional, Hotchkiss, Richard S., additional, Presti, Rachel M., additional, O’Halloran, Jane A., additional, Powderly, William G., additional, Thomas, Paul G., additional, and Ellebedy, Ali H., additional

Published
2023
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7. mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

Author

Zimmerman, Ofer, Altman Doss, Alexa Michelle, Kaplonek, Paulina, Liang, Chieh-Yu, VanBlargan, Laura A., Chen, Rita E., Monroy, Jennifer Marie, Wedner, H. James, Kulczycki, Anthony, Jr., Mantia, Tarisa L., O’Shaughnessy, Caitlin C., Davis-Adams, Hannah G., Bertera, Harry L., Adams, Lucas J., Raju, Saravanan, Zhao, Fang R., Rigell, Christopher J., Dy, Tiffany Biason, Kau, Andrew L., Ren, Zhen, Turner, Jackson S., O’Halloran, Jane A., Presti, Rachel M., Fremont, Daved H., Kendall, Peggy L., Ellebedy, Ali H., Alter, Galit, and Diamond, Michael S.

Published
2022
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8. Germinal centre-driven maturation of B cell response to mRNA vaccination

Author

Kim, Wooseob, Zhou, Julian Q., Horvath, Stephen C., Schmitz, Aaron J., Sturtz, Alexandria J., Lei, Tingting, Liu, Zhuoming, Kalaidina, Elizaveta, Thapa, Mahima, Alsoussi, Wafaa B., Haile, Alem, Klebert, Michael K., Suessen, Teresa, Parra-Rodriguez, Luis, Mudd, Philip A., Whelan, Sean P. J., Middleton, William D., Teefey, Sharlene A., Pusic, Iskra, O’Halloran, Jane A., Presti, Rachel M., Turner, Jackson S., and Ellebedy, Ali H.

Published
2022
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9. Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin.

Author

Berndsen, Zachary T., Akhtar, Marjahan, Thapa, Mahima, Vickers, Tim J., Schmitz, Aaron, Torres, Jonathan L., Baboo, Sabyasachi, Kumar, Pardeep, Khatoon, Nazia, Sheikh, Alaullah, Hamrick, Melissa, Diedrich, Jolene K., Martinez-Bartolome, Salvador, Garrett, Patrick T., Yates III, John R., Turner, Jackson S., Laird, Renee M., Poly, Frédéric, Porter, Chad K., and Copps, Jeffrey

Subjects
BLOOD groups, ESCHERICHIA coli, GLYCAN structure, INTESTINAL mucosa, BACTERIAL adhesion, IMMUNOGLOBULINS, MONOCLONAL antibodies
Abstract

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design. Author summary: Enterotoxigenic E. coli (ETEC), a leading cause of diarrhea disproportionately affecting young children in low-income regions, are a priority for vaccine development. Individuals possessing A blood-type are more susceptible to severe cholera-like disease. EtpA, a secreted, immunogenic, blood group A binding protein, is a current vaccine target antigen. Here, we determined the structure of EtpA in complex with protective as well as non-protective monoclonal antibodies targeting two different domains of the protein, pinpointing key regions involved in blood-group A antigen recognition and uncovering the mechanism of antibody-based protection. In addition, we show through mass-spectrometry that EtpA is extensively and heterogeneously glycosylated at surface-exposed asparagine residues by a promiscuous and low-fidelity glycosyltransferase, EtpC, and that this unique form of bacterial glycosylation is critical for to development of protective immune responses. Lastly, polyclonal antibodies from vaccinated mice as well as monoclonal antibodies obtained from ETEC-infected volunteers revealed that the highly antigenic surface of EtpA exhibits both protective and non-protective epitopes. These results greatly expand our understanding of ETEC pathogenesis, and the immune responses elicited by these common infections, providing valuable information to aid in the rational design and testing of subunit vaccines. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors

Author

Chen, Rita E., Gorman, Matthew J., Zhu, Daniel Y., Carreño, Juan Manuel, Yuan, Dansu, VanBlargan, Laura A., Burdess, Samantha, Lauffenburger, Douglas A., Kim, Wooseob, Turner, Jackson S., Droit, Lindsay, Handley, Scott A., Chahin, Salim, Deepak, Parakkal, O’Halloran, Jane A., Paley, Michael A., Presti, Rachel M., Wu, Gregory F., Krammer, Florian, Alter, Galit, Ellebedy, Ali H., Kim, Alfred H.J., and Diamond, Michael S.

Published
2021
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11. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

Author

Ahmed, Bulbul, Altman, Deena, Amoako, Angela, Awawda, Mahmoud, Beach, Katherine, Bermúdez-González, Carolina, Chernet, Rachel, Eaker, Lily, Fabre, Shelcie, Ferreri, Emily D., Floda, Daniel, Gleason, Charles, Kleiner, Giulio, Jurczyszak, Denise, Matthews, Julia, Mendez, Wanni, Mulder, Lubbertus C.F., Polanco, Jose, Russo, Kayla, Salimbangon, Ashley, Saksena, Miti, Shin, Amber S., Sominsky, Levy, Suthakaran, Sayahi, Wajnberg, Ania, Amanat, Fatima, Thapa, Mahima, Lei, Tinting, Ahmed, Shaza M. Sayed, Adelsberg, Daniel C., Carreño, Juan Manuel, Strohmeier, Shirin, Schmitz, Aaron J., Zafar, Sarah, Zhou, Julian Q., Rijnink, Willemijn, Alshammary, Hala, Borcherding, Nicholas, Reiche, Ana Gonzalez, Srivastava, Komal, Sordillo, Emilia Mia, van Bakel, Harm, Turner, Jackson S., Bajic, Goran, Simon, Viviana, Ellebedy, Ali H., and Krammer, Florian

Published
2021
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12. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans

Author

Turner, Jackson S., Kim, Wooseob, Kalaidina, Elizaveta, Goss, Charles W., Rauseo, Adriana M., Schmitz, Aaron J., Hansen, Lena, Haile, Alem, Klebert, Michael K., Pusic, Iskra, O'Halloran, Jane A., and Presti, Rachel M.

Subjects
Bone marrow -- Health aspects, Plasma cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies.sup.1-7. Individuals who have recovered from COVID-19 have a substantially lower risk of reinfection with SARS-CoV-2.sup.8-10. Nonetheless, it has been reported that levels of anti-SARS-CoV-2 serum antibodies decrease rapidly in the first few months after infection, raising concerns that long-lived BMPCs may not be generated and humoral immunity against SARS-CoV-2 may be short-lived.sup.11-13. Here we show that in convalescent individuals who had experienced mild SARS-CoV-2 infections (n = 77), levels of serum anti-SARS-CoV-2 spike protein (S) antibodies declined rapidly in the first 4 months after infection and then more gradually over the following 7 months, remaining detectable at least 11 months after infection. Anti-S antibody titres correlated with the frequency of S-specific plasma cells in bone marrow aspirates from 18 individuals who had recovered from COVID-19 at 7 to 8 months after infection. S-specific BMPCs were not detected in aspirates from 11 healthy individuals with no history of SARS-CoV-2 infection. We show that S-binding BMPCs are quiescent, which suggests that they are part of a stable compartment. Consistently, circulating resting memory B cells directed against SARS-CoV-2 S were detected in the convalescent individuals. Overall, our results indicate that mild infection with SARS-CoV-2 induces robust antigen-specific, long-lived humoral immune memory in humans. SARS-CoV-2 infection induces long-lived bone marrow plasma cells that correlate with anti-SARS-CoV-2 spike protein antibody titres in individuals who have recovered from COVID-19., Author(s): Jackson S. Turner [sup.1] , Wooseob Kim [sup.1] , Elizaveta Kalaidina [sup.2] , Charles W. Goss [sup.3] , Adriana M. Rauseo [sup.4] , Aaron J. Schmitz [sup.1] , Lena [...]

Published
2021
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13. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses

Author

Turner, Jackson S., O’Halloran, Jane A., Kalaidina, Elizaveta, Kim, Wooseob, Schmitz, Aaron J., Zhou, Julian Q., Lei, Tingting, Thapa, Mahima, Chen, Rita E., Case, James Brett, Amanat, Fatima, Rauseo, Adriana M., Haile, Alem, Xie, Xuping, Klebert, Michael K., Suessen, Teresa, Middleton, William D., Shi, Pei-Yong, Krammer, Florian, Teefey, Sharlene A., Diamond, Michael S., Presti, Rachel M., and Ellebedy, Ali H.

Published
2021
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14. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Author

Chen, Rita E., Zhang, Xianwen, Case, James Brett, Winkler, Emma S., Liu, Yang, VanBlargan, Laura A., Liu, Jianying, Errico, John M., Xie, Xuping, Suryadevara, Naveenchandra, Gilchuk, Pavlo, Zost, Seth J., Tahan, Stephen, Droit, Lindsay, Turner, Jackson S., Kim, Wooseob, and Schmitz, Aaron

Subjects
Viral drug resistance -- Research, Monoclonal antibodies -- Research, Virus research, Biological sciences, Health
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo. A comprehensive analysis of antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants shows markedly diminished neutralizing activity against the variant B.1.351, first identified in South Africa., Author(s): Rita E. Chen [sup.1] [sup.2] , Xianwen Zhang [sup.3] , James Brett Case [sup.1] , Emma S. Winkler [sup.1] [sup.2] , Yang Liu [sup.3] , Laura A. VanBlargan [sup.1] [...]

Published
2021
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16. Immunoglobulin replacement products confer in vivo protection against SARS-CoV-2 XBB.1.5 Omicron variant despite poor neutralizing activity

Author

Zimmerman, Ofer, primary, Altman Doss, Alexa Michelle, additional, Ying, Baoling, additional, Liang, Chieh-Yu, additional, Mackin, Samantha R., additional, Davis-Adams, Hannah G., additional, Adams, Lucas J., additional, VanBlargan, Laura A., additional, Chen, Rita E., additional, Scheaffer, Suzanne M., additional, Desai, Pritesh, additional, Raju, Saravanan, additional, Mantia, Tarisa L., additional, O'Shaughnessy, Caitlin C., additional, Monroy, Jennifer M., additional, Wedner, H. James, additional, Rigell, Christpher J., additional, Kau, Andrew L., additional, Dy, Tiffany B., additional, Ren, Zhen, additional, Turner, Jackson S., additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Kendall, Peggy L., additional, Fremont, Daved H., additional, Ellebedy, Ali H., additional, and Diamond, Michael S., additional

Published
2024
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17. Human germinal centres engage memory and naive B cells after influenza vaccination

Author

Turner, Jackson S., Zhou, Julian Q., Han, Julianna, Schmitz, Aaron J., Rizk, Amena A., Alsoussi, Wafaa B., Lei, Tingting, Amor, Mostafa, McIntire, Katherine M., Meade, Philip, Strohmeier, Shirin, Brent, Rafael I., Richey, Sara T., Haile, Alem, Yang, Yuhe R., Klebert, Michael K., Suessen, Teresa, Teefey, Sharlene, Presti, Rachel M., Krammer, Florian, Kleinstein, Steven H., Ward, Andrew B., and Ellebedy, Ali H.

Published
2020
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18. Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase

Author

Lei, Ruipeng, primary, Kim, Wooseob, additional, Lv, Huibin, additional, Mou, Zongjun, additional, Scherm, Michael J., additional, Schmitz, Aaron J., additional, Turner, Jackson S., additional, Tan, Timothy J.C., additional, Wang, Yiquan, additional, Ouyang, Wenhao O., additional, Liang, Weiwen, additional, Rivera-Cardona, Joel, additional, Teo, Chuyun, additional, Graham, Claire S., additional, Brooke, Christopher B., additional, Presti, Rachel M., additional, Mok, Chris K.P., additional, Krammer, Florian, additional, Dai, Xinghong, additional, Ellebedy, Ali H., additional, and Wu, Nicholas C., additional

Published
2023
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19. Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination

Author

Schattgen, Stefan, primary, Turner, Jackson S, additional, Ghonim, Mohamed A, additional, Crawford, Jeremy Chase, additional, Schmitz, Aaron J, additional, Kim, Hyunjin, additional, Zhou, Julian Q, additional, Awad, Walid, additional, Kim, Wooseob, additional, McIntire, Katherine M, additional, Haile, Alem, additional, Klebert, Michael K, additional, Suessen, Teresa, additional, Middleton, William D, additional, Teefey, Sharlene A, additional, Presti, Rachel M, additional, Ellebedy, Ali, additional, and Thomas, Paul, additional

Published
2023
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20. CD4+T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

Author

Borcherding, Nicholas, Kim, Wooseob, Quinn, Michael, Han, Fangjie, Zhou, Julian Q., Sturtz, Alexandria J., Schmitz, Aaron J., Lei, Tingting, Schattgen, Stefan A., Klebert, Michael K., Suessen, Teresa, Middleton, William D., Goss, Charles W., Liu, Chang, Crawford, Jeremy Chase, Thomas, Paul G., Teefey, Sharlene A., Presti, Rachel M., O’Halloran, Jane A., Turner, Jackson S., Ellebedy, Ali H., and Mudd, Philip A.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4+T cell responses. Using single-cell transcriptomics, here, we evaluated CD4+T cells specific for the SARS-CoV-2 spike protein in the blood and draining lymph nodes (dLNs) of individuals 3 months and 6 months after vaccination with the BNT162b2 mRNA vaccine. We analyzed 1,277 spike-specific CD4+T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4+follicular helper T (TFH) cells exhibited heterogeneous phenotypes, including germinal center CD4+TFHcells and CD4+IL-10+TFHcells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4+T cell profiles in blood that were distinct from those detected in blood 3 months and 6 months after BNT162b2 vaccination. Our findings provide an atlas of human spike-specific CD4+T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection.

Published
2024
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21. Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination

Author

Quinn, Michael, primary, Parra-Rodriguez, Luis, additional, Alsoussi, Wafaa B., additional, Ayres, Chapelle, additional, Klebert, Michael K., additional, Liu, Chang, additional, Suessen, Teresa, additional, Scheaffer, Suzanne M., additional, Middleton, William D., additional, Teefey, Sharlene A., additional, Powderly, William G., additional, Diamond, Michael S., additional, Presti, Rachel M., additional, Ellebedy, Ali H., additional, Turner, Jackson S., additional, O’Halloran, Jane A., additional, and Mudd, Philip A., additional

Published
2023
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23. SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

Author

Lin, Frank J., primary, Doss, Alexa Michelle Altman, additional, Davis-Adams, Hannah G., additional, Adams, Lucas J., additional, Hanson, Christopher H., additional, VanBlargan, Laura A., additional, Liang, Chieh-Yu, additional, Chen, Rita E., additional, Monroy, Jennifer Marie, additional, Wedner, H. James, additional, Kulczycki, Anthony, additional, Mantia, Tarisa L., additional, O’Shaughnessy, Caitlin C., additional, Raju, Saravanan, additional, Zhao, Fang R., additional, Rizzi, Elise, additional, Rigell, Christopher J., additional, Dy, Tiffany Biason, additional, Kau, Andrew L., additional, Ren, Zhen, additional, Turner, Jackson S., additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Fremont, Daved H., additional, Kendall, Peggy L., additional, Ellebedy, Ali H., additional, Mudd, Philip A., additional, Diamond, Michael S., additional, Zimmerman, Ofer, additional, and Laidlaw, Brian J., additional

Published
2022
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24. SARS-CoV-2 Omicron boosting induces de novo B cell response in humans

Author

Alsoussi, Wafaa B., primary, Malladi, Sameer K., additional, Zhou, Julian Q., additional, Liu, Zhuoming, additional, Ying, Baoling, additional, Kim, Wooseob, additional, Schmitz, Aaron J., additional, Lei, Tingting, additional, Horvath, Stephen C., additional, Sturtz, Alexandria J., additional, McIntire, Katherine M., additional, Evavold, Birk, additional, Han, Fangjie, additional, Scheaffer, Suzanne M., additional, Fox, Isabella F., additional, Parra-Rodriguez, Luis, additional, Nachbagauer, Raffael, additional, Nestorova, Biliana, additional, Chalkias, Spyros, additional, Farnsworth, Christopher W., additional, Klebert, Michael K., additional, Pusic, Iskra, additional, Strnad, Benjamin S., additional, Middleton, William D., additional, Teefey, Sharlene A., additional, Whelan, Sean P.J., additional, Diamond, Michael S., additional, Paris, Robert, additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Turner, Jackson S., additional, and Ellebedy, Ali H., additional

Published
2022
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25. Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 Omicron Variant in Adolescents and Adults

Author

Gupta, Sneh Lata, primary, Mantus, Grace, additional, Manning, Kelly E., additional, Ellis, Madison, additional, Patel, Mit, additional, Ciric, Caroline Rose, additional, Lu, Austin, additional, Turner, Jackson S., additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Joshi, Devyani Jaideep, additional, Ellebedy, Ali H., additional, Anderson, Evan J., additional, Rostad, Christina A., additional, Suthar, Mehul S., additional, and Wrammert, Jens, additional

Published
2022
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27. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans

Author

Mudd, Philip A., primary, Minervina, Anastasia A., additional, Pogorelyy, Mikhail V., additional, Turner, Jackson S., additional, Kim, Wooseob, additional, Kalaidina, Elizaveta, additional, Petersen, Jan, additional, Schmitz, Aaron J., additional, Lei, Tingting, additional, Haile, Alem, additional, Kirk, Allison M., additional, Mettelman, Robert C., additional, Crawford, Jeremy Chase, additional, Nguyen, Thi H.O., additional, Rowntree, Louise C., additional, Rosati, Elisa, additional, Richards, Katherine A., additional, Sant, Andrea J., additional, Klebert, Michael K., additional, Suessen, Teresa, additional, Middleton, William D., additional, Wolf, Joshua, additional, Teefey, Sharlene A., additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Kedzierska, Katherine, additional, Rossjohn, Jamie, additional, Thomas, Paul G., additional, Ellebedy, Ali H., additional, Estepp, Jeremie H., additional, Schultz-Cherry, Stacey, additional, McGargill, Maureen A., additional, Gaur, Aditya, additional, Hoffman, James, additional, Mori, Motomi, additional, Tang, Li, additional, Tuomanen, Elaine, additional, Webby, Richard, additional, Hayden, Randall T., additional, Hakim, Hana, additional, Hijano, Diego R., additional, Allison, Kim J., additional, Allen, E. Kaitlynn, additional, Bajracharya, Resha, additional, Awad, Walid, additional, Van de Velde, Lee-Ann, additional, Clark, Brandi L., additional, Wilson, Taylor L., additional, Souquette, Aisha, additional, Castellaw, Ashley, additional, Dallas, Ronald H., additional, Gowen, Ashleigh, additional, Fabrizio, Thomas P., additional, Lin, Chun-Yang, additional, Brice, David C., additional, Cherry, Sean, additional, Roubidoux, Ericka Kirkpatrick, additional, Cortez, Valerie, additional, Freiden, Pamela, additional, Wohlgemuth, Nicholas, additional, and Whitt, Kendall, additional

Published
2022
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29. Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

Author

Kim, Wooseob, primary, Zhou, Julian Q., additional, Sturtz, Alexandria J., additional, Horvath, Stephen C., additional, Schmitz, Aaron J., additional, Lei, Tingting, additional, Kalaidina, Elizaveta, additional, Thapa, Mahima, additional, Alsoussi, Wafaa B., additional, Haile, Alem, additional, Klebert, Michael K., additional, Suessen, Teresa, additional, Parra-Rodriguez, Luis, additional, Mudd, Philip A., additional, Middleton, William D., additional, Teefey, Sharlene A., additional, Pusic, Iskra, additional, O’Halloran, Jane A., additional, Presti, Rachel M., additional, Turner, Jackson S., additional, and Ellebedy, Ali H., additional

Published
2021
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31. Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

Author

Su, Wen, primary, Sia, Sin Fun, additional, Schmitz, Aaron J., additional, Bricker, Traci L., additional, Starr, Tyler N., additional, Greaney, Allison J., additional, Turner, Jackson S., additional, Mohammed, Bassem M., additional, Liu, Zhuoming, additional, Choy, Ka Tim, additional, Darling, Tamarand L., additional, Joshi, Astha, additional, Cheng, Ka Man, additional, Wong, Alvina Y. L., additional, Harastani, Houda H., additional, Nicholls, John M., additional, Whelan, Sean P. J., additional, Bloom, Jesse D., additional, Yen, Hui-Ling, additional, Ellebedy, Ali H., additional, and Boon, Adrianus C. M., additional

Published
2021
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32. Reduced antibody activity against SARS-CoV-2 B.1.617.2 Delta virus in serum of mRNA-vaccinated patients receiving TNF-α inhibitors

Author

Chen, Rita E., primary, Gorman, Matthew J., additional, Zhu, Daniel Y., additional, Carreño, Juan Manuel, additional, Yuan, Dansu, additional, VanBlargan, Laura A., additional, Burdess, Samantha, additional, Lauffenburger, Douglas A., additional, Kim, Wooseob, additional, Turner, Jackson S., additional, Droit, Lindsay, additional, Handley, Scott A., additional, Chahin, Salim, additional, Deepak, Parakkal, additional, O’Halloran, Jane A., additional, Paley, Michael, additional, Presti, Rachel M., additional, Wu, Gregory F., additional, Krammer, Florian, additional, Alter, Galit, additional, Ellebedy, Ali H., additional, Kim, Alfred H. J., additional, and Diamond, Michael S., additional

Published
2021
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33. A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

Author

Schmitz, Aaron J., primary, Turner, Jackson S., additional, Liu, Zhuoming, additional, Zhou, Julian Q., additional, Aziati, Ishmael D., additional, Chen, Rita E., additional, Joshi, Astha, additional, Bricker, Traci L., additional, Darling, Tamarand L., additional, Adelsberg, Daniel C., additional, Altomare, Clara G., additional, Alsoussi, Wafaa B., additional, Case, James Brett, additional, VanBlargan, Laura A., additional, Lei, Tingting, additional, Thapa, Mahima, additional, Amanat, Fatima, additional, Jeevan, Trushar, additional, Fabrizio, Thomas, additional, O’Halloran, Jane A., additional, Shi, Pei-Yong, additional, Presti, Rachel M., additional, Webby, Richard J., additional, Krammer, Florian, additional, Whelan, Sean P.J., additional, Bajic, Goran, additional, Diamond, Michael S., additional, Boon, Adrianus C.M., additional, and Ellebedy, Ali H., additional

Published
2021
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34. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

Author

Amanat, Fatima, primary, Thapa, Mahima, additional, Lei, Tinting, additional, Ahmed, Shaza M. Sayed, additional, Adelsberg, Daniel C., additional, Carreño, Juan Manuel, additional, Strohmeier, Shirin, additional, Schmitz, Aaron J., additional, Zafar, Sarah, additional, Zhou, Julian Q., additional, Rijnink, Willemijn, additional, Alshammary, Hala, additional, Borcherding, Nicholas, additional, Reiche, Ana Gonzalez, additional, Srivastava, Komal, additional, Sordillo, Emilia Mia, additional, van Bakel, Harm, additional, Turner, Jackson S., additional, Bajic, Goran, additional, Simon, Viviana, additional, Ellebedy, Ali H., additional, Krammer, Florian, additional, Ahmed, Bulbul, additional, Altman, Deena, additional, Amoako, Angela, additional, Awawda, Mahmoud, additional, Beach, Katherine, additional, Bermúdez-González, Carolina, additional, Chernet, Rachel, additional, Eaker, Lily, additional, Fabre, Shelcie, additional, Ferreri, Emily D., additional, Floda, Daniel, additional, Gleason, Charles, additional, Kleiner, Giulio, additional, Jurczyszak, Denise, additional, Matthews, Julia, additional, Mendez, Wanni, additional, Mulder, Lubbertus C.F., additional, Polanco, Jose, additional, Russo, Kayla, additional, Salimbangon, Ashley, additional, Saksena, Miti, additional, Shin, Amber S., additional, Sominsky, Levy, additional, Suthakaran, Sayahi, additional, and Wajnberg, Ania, additional

Published
2021
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35. Distinct peripheral inflammatory profiles distinguish COVID-19 from influenza infection, with limited contributions from cytokine storm

Author

Crawford, Jeremy Chase, primary, Mudd, Philip A., additional, Turner, Jackson S., additional, Souquette, Aisha, additional, Reynolds, Daniel, additional, Bender, Diane, additional, Bosanquet, James, additional, Anand, Nitin J., additional, Striker, David A., additional, Martin, R. Scott, additional, Boon, Adrianus C.M., additional, House, Stacey L., additional, Remy, Kenneth E., additional, Hotchkiss, Richard, additional, Presti, Rachel, additional, O’Halloran, Jane, additional, Powderly, William G., additional, Thomas, Paul Glyndwr, additional, and Ellebedy, Ali H., additional

Published
2021
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36. A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

Author

Schmitz, Aaron J., primary, Turner, Jackson S., additional, Liu, Zhuoming, additional, Aziati, Ishmael D., additional, Chen, Rita E., additional, Joshi, Astha, additional, Bricker, Traci L., additional, Darling, Tamarand L., additional, Adelsberg, Daniel C., additional, Alsoussi, Wafaa B., additional, Case, James Brett, additional, Lei, Tingting, additional, Thapa, Mahima, additional, Amanat, Fatima, additional, O’Halloran, Jane A., additional, Shi, Pei-Yong, additional, Presti, Rachel M., additional, Krammer, Florian, additional, Bajic, Goran, additional, Whelan, Sean P.J., additional, Diamond, Michael S., additional, Boon, Adrianus C. M., additional, and Ellebedy, Ali H., additional

Published
2021
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39. Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm

Author

Mudd, Philip A., primary, Crawford, Jeremy Chase, additional, Turner, Jackson S., additional, Souquette, Aisha, additional, Reynolds, Daniel, additional, Bender, Diane, additional, Bosanquet, James P., additional, Anand, Nitin J., additional, Striker, David A., additional, Martin, R. Scott, additional, Boon, Adrianus C. M., additional, House, Stacey L., additional, Remy, Kenneth E., additional, Hotchkiss, Richard S., additional, Presti, Rachel M., additional, O’Halloran, Jane A., additional, Powderly, William G., additional, Thomas, Paul G., additional, and Ellebedy, Ali H., additional

Published
2020
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41. SARS‐CoV‐2 mRNAVaccination Causes Prolonged Increased Cortical Thickening and Vascularity in Ipsilateral Axillary Lymph Nodes

Author

Teefey, Sharlene A., Middleton, William D., Turner, Jackson S., Ellebedy, Ali H., Suessen, Teresa, Wallendorf, Michael, O'Halloran, Jane A., and Presti, Rachel

Abstract

To describe the serial grey‐scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer‐BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS‐CoV‐2) messenger RNA (mRNA) vaccine over 24 to 28 weeks. The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey‐scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. A total of 11 lateral lymph nodes were identified. Cortical thickness was measured and absence or presence of color Doppler flow in the hilum and lymph node cortex was graded (scale: 0–2). Eleven lateral axillary lymph nodes were biopsied over 24 to 28 weeks. Mean thickness varied through time (P< .001) and was greater weeks 2 to 7 compared to weeks 24 to 28 (mean differences of 2.6 to 1.3; P< .006), but weeks 14 to 17 mean thickness was not different from weeks 24 to 28 (0.57; P= .15). Cortical vascularity was increased in all 11 lymph nodes by week 5. Mean vascularity varied through time (P< .001) and was greater weeks 2 to 14 compared to weeks 24 to 28; mean differences ranged from 1.7 to 0.83 (P< .001). Serial grey‐scale and color Doppler appearance of ipsilateral axillary lymph nodes after mRNA vaccination manifest as increased and prolonged cortical thickening and vascularity that diminishes and approaches normal by 24 to 28 weeks.

Published
2022
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42. Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective

Author

Madsen, Anders, primary, Dai, Ya-Nan, additional, McMahon, Meagan, additional, Schmitz, Aaron J., additional, Turner, Jackson S., additional, Tan, Jessica, additional, Lei, Tingting, additional, Alsoussi, Wafaa B., additional, Strohmeier, Shirin, additional, Amor, Mostafa, additional, Mohammed, Bassem M., additional, Mudd, Philip A., additional, Simon, Viviana, additional, Cox, Rebecca J., additional, Fremont, Daved H., additional, Krammer, Florian, additional, and Ellebedy, Ali H., additional

Published
2020
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43. A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

Author

Alsoussi, Wafaa B., primary, Turner, Jackson S., additional, Case, James B., additional, Zhao, Haiyan, additional, Schmitz, Aaron J., additional, Zhou, Julian Q., additional, Chen, Rita E., additional, Lei, Tingting, additional, Rizk, Amena A., additional, McIntire, Katherine M., additional, Winkler, Emma S., additional, Fox, Julie M., additional, Kafai, Natasha M., additional, Thackray, Larissa B., additional, Hassan, Ahmed O., additional, Amanat, Fatima, additional, Krammer, Florian, additional, Watson, Corey T., additional, Kleinstein, Steven H., additional, Fremont, Daved H., additional, Diamond, Michael S., additional, and Ellebedy, Ali H., additional

Published
2020
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44. A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies

Author

Hassan, Ahmed O., primary, Case, James Brett, additional, Winkler, Emma S., additional, Thackray, Larissa B., additional, Kafai, Natasha M., additional, Bailey, Adam L., additional, McCune, Broc T., additional, Fox, Julie M., additional, Chen, Rita E., additional, Alsoussi, Wafaa B., additional, Turner, Jackson S., additional, Schmitz, Aaron J., additional, Lei, Tingting, additional, Shrihari, Swathi, additional, Keeler, Shamus P., additional, Fremont, Daved H., additional, Greco, Suellen, additional, McCray, Paul B., additional, Perlman, Stanley, additional, Holtzman, Michael J., additional, Ellebedy, Ali H., additional, and Diamond, Michael S., additional

Published
2020
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45. Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease

Author

Mudd, Philip A, primary, Crawford, Jeremy Chase, additional, Turner, Jackson S, additional, Souquette, Aisha, additional, Reynolds, Daniel, additional, Bender, Diane, additional, Bosanquet, James P., additional, Anand, Nitin J., additional, Striker, David A., additional, Martin, R. Scott, additional, Boon, Adrianus C. M., additional, House, Stacey L., additional, Remy, Kenneth E., additional, Hotchkiss, Richard S., additional, Presti, Rachel M., additional, OHalloran, Jane A., additional, Powderly, William G., additional, Thomas, Paul G., additional, and Ellebedy, Ali H., additional

Published
2020
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48. Distinct peripheral inflammatory profiles distinguish COVID-19 from influenza infection, with limited contributions from cytokine storm

Author

Jeremy Chase Crawford, Mudd, Philip A., Turner, Jackson S., Souquette, Aisha, Reynolds, Daniel, Bender, Diane, Bosanquet, James, Anand, Nitin J., Striker, David A., Martin, R. Scott, Boon, Adrianus C. M., House, Stacey L., Remy, Kenneth E., Hotchkiss, Richard, Presti, Rachel, O Halloran, Jane, Powderly, William G., Thomas, Paul Glyndwr, and Ellebedy, Ali H.

Subjects
Immunology, Immunology and Allergy
Abstract

We developed a prospective observational cohort of COVID-19 and influenza patients to assess the quality and magnitude of their immune responses at the cellular and protein levels. Although COVID-19 patients exhibited equivalent lymphocyte counts compared to influenza patients, they had fewer monocytes and lower surface HLA-class II expression on select monocyte populations compared to influenza patients and healthy controls. Decreased HLA-DR on intermediate monocytes was a significant predictor of COVID-19 disease severity. Protein cytokine levels were measured in two distinct COVID-19 cohorts, composed of 73 and 89 patients, revealing multiple inflammatory phenotypes. Only four percent of patients (7 of 162) exhibited a distinct Cytokine Storm Syndrome (CSS) phenotype. Furthermore, COVID-19 patients generally exhibited lower cytokine levels than influenza patients. Upregulation of a few innate inflammatory mediators, including IL-6, GCSF, IL-1RA, and MCP1, predicted death from acute respiratory failure among COVID-19 patients but were not statistically higher than those of influenza patients. Single-cell transcriptional profiling of 2 healthy controls as well as 3 COVID-19 and 3 influenza subjects with respiratory failure was concordant with the profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple cell types. In contrast, COVID-19 cells were enriched for alterations in metabolic, stress, and apoptotic pathways. When considered across the spectrum of peripheral innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct, with COVID-19 patients generally less inflamed than those with influenza.

Published
2021
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49. Maturation of germinal center B cells after influenza virus vaccination in humans

Author

McIntire, Katherine M., Meng, Hailong, Lin, Ting-Hui, Kim, Wooseob, Moore, Nina E., Han, Julianna, McMahon, Meagan, Wang, Meng, Malladi, Sameer Kumar, Mohammed, Bassem M., Zhou, Julian Q., Schmitz, Aaron J., Hoehn, Kenneth B., Carreño, Juan Manuel, Yellin, Temima, Suessen, Teresa, Middleton, William D., Teefey, Sharlene A., Presti, Rachel M., Krammer, Florian, Turner, Jackson S., Ward, Andrew B., Wilson, Ian A., Kleinstein, Steven H., and Ellebedy, Ali H.

Abstract

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.

Published
2024
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50. Broadly protective human antibodies that target the active site of influenza virus neuraminidase

Author

Stadlbauer, Daniel, primary, Zhu, Xueyong, additional, McMahon, Meagan, additional, Turner, Jackson S., additional, Wohlbold, Teddy J., additional, Schmitz, Aaron J., additional, Strohmeier, Shirin, additional, Yu, Wenli, additional, Nachbagauer, Raffael, additional, Mudd, Philip A., additional, Wilson, Ian A., additional, Ellebedy, Ali H., additional, and Krammer, Florian, additional

Published
2019
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