This page has only limited features, please log in for full access.

Unclaimed
Patrick C. Wilson
University of Chicago

Basic Info

Basic Info is private.

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Journal article
Published: 23 July 2021 in Cell Reports Methods
Reads 0
Downloads 0

Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells).

ACS Style

Lei Li; Haley L. Dugan; Christopher T. Stamper; Linda Yu-Ling Lan; Nicholas W. Asby; Matthew Knight; Olivia Stovicek; Nai-Ying Zheng; Maria Lucia Madariaga; Kumaran Shanmugarajah; Maud O. Jansen; Siriruk Changrob; Henry A. Utset; Carole Henry; Christopher Nelson; Robert P. Jedrzejczak; Daved H. Fremont; Andrzej Joachimiak; Florian Krammer; Jun Huang; Aly A. Khan; Patrick C. Wilson. Improved integration of single-cell transcriptome and surface protein expression by LinQ-View. Cell Reports Methods 2021, 1, 100056 .

AMA Style

Lei Li, Haley L. Dugan, Christopher T. Stamper, Linda Yu-Ling Lan, Nicholas W. Asby, Matthew Knight, Olivia Stovicek, Nai-Ying Zheng, Maria Lucia Madariaga, Kumaran Shanmugarajah, Maud O. Jansen, Siriruk Changrob, Henry A. Utset, Carole Henry, Christopher Nelson, Robert P. Jedrzejczak, Daved H. Fremont, Andrzej Joachimiak, Florian Krammer, Jun Huang, Aly A. Khan, Patrick C. Wilson. Improved integration of single-cell transcriptome and surface protein expression by LinQ-View. Cell Reports Methods. 2021; 1 (4):100056.

Chicago/Turabian Style

Lei Li; Haley L. Dugan; Christopher T. Stamper; Linda Yu-Ling Lan; Nicholas W. Asby; Matthew Knight; Olivia Stovicek; Nai-Ying Zheng; Maria Lucia Madariaga; Kumaran Shanmugarajah; Maud O. Jansen; Siriruk Changrob; Henry A. Utset; Carole Henry; Christopher Nelson; Robert P. Jedrzejczak; Daved H. Fremont; Andrzej Joachimiak; Florian Krammer; Jun Huang; Aly A. Khan; Patrick C. Wilson. 2021. "Improved integration of single-cell transcriptome and surface protein expression by LinQ-View." Cell Reports Methods 1, no. 4: 100056.

Preprint content
Published: 19 July 2021 in Research Square
Reads 0
Downloads 0

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484 and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and the variants of concern, including B.1.1.7 (alpha), P.1 (gamma) and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to wildtype (WT) SARS-CoV-2 do possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.

ACS Style

Patrick Wilson; Siriruk Changrob; Yanbin Fu; Jenna Guthmiller; Peter Halfmann; Lei Li; Christopher Stamper; Haley Dugan; Molly Accola; William Rehrauer; Nai-Ying Zheng; Min Huang; Jiaolong Wang; Steven Erickson; Henry Utset; Hortencia Graves; Fatima Amanat; D. Noah Sather; Florian Krammer; Yoshihiro Kawaoka. Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike. Research Square 2021, 1 .

AMA Style

Patrick Wilson, Siriruk Changrob, Yanbin Fu, Jenna Guthmiller, Peter Halfmann, Lei Li, Christopher Stamper, Haley Dugan, Molly Accola, William Rehrauer, Nai-Ying Zheng, Min Huang, Jiaolong Wang, Steven Erickson, Henry Utset, Hortencia Graves, Fatima Amanat, D. Noah Sather, Florian Krammer, Yoshihiro Kawaoka. Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike. Research Square. 2021; ():1.

Chicago/Turabian Style

Patrick Wilson; Siriruk Changrob; Yanbin Fu; Jenna Guthmiller; Peter Halfmann; Lei Li; Christopher Stamper; Haley Dugan; Molly Accola; William Rehrauer; Nai-Ying Zheng; Min Huang; Jiaolong Wang; Steven Erickson; Henry Utset; Hortencia Graves; Fatima Amanat; D. Noah Sather; Florian Krammer; Yoshihiro Kawaoka. 2021. "Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike." Research Square , no. : 1.

Review
Published: 01 July 2021 in Vaccines
Reads 0
Downloads 0

The generation of high affinity antibodies is a crucial aspect of immunity induced by vaccination or infection. Investigation into the B cells that produce these antibodies grants key insights into the effectiveness of novel immunogens to induce a lasting protective response against endemic or pandemic pathogens, such as influenza viruses, human immunodeficiency virus, or severe acute respiratory syndrome coronavirus-2. However, humoral immunity has largely been studied at the serological level, limiting our knowledge on the specificity and function of B cells recruited to respond to pathogens. In this review, we cover a number of recent innovations in the field that have increased our ability to connect B cell function to the B cell repertoire and antigen specificity. Moreover, we will highlight recent advances in the development of both ex vivo and in vivo models to study human B cell responses. Together, the technologies highlighted in this review can be used to help design and validate new vaccine designs and platforms.

ACS Style

Henry Utset; Jenna Guthmiller; Patrick Wilson. Bridging the B Cell Gap: Novel Technologies to Study Antigen-Specific Human B Cell Responses. Vaccines 2021, 9, 711 .

AMA Style

Henry Utset, Jenna Guthmiller, Patrick Wilson. Bridging the B Cell Gap: Novel Technologies to Study Antigen-Specific Human B Cell Responses. Vaccines. 2021; 9 (7):711.

Chicago/Turabian Style

Henry Utset; Jenna Guthmiller; Patrick Wilson. 2021. "Bridging the B Cell Gap: Novel Technologies to Study Antigen-Specific Human B Cell Responses." Vaccines 9, no. 7: 711.

Journal article
Published: 29 June 2021 in mBio
Reads 0
Downloads 0

Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess different glycosylation patterns than viruses circulating among humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived glycan that is an antigenic decoy, with egg-binding MAbs reacting with a sulfated N -acetyllactosamine (LacNAc).

ACS Style

Jenna J. Guthmiller; Henry A. Utset; Carole Henry; Lei Li; Nai-Ying Zheng; Weina Sun; Marcos Costa Vieira; Seth Zost; Min Huang; Scott E. Hensley; Sarah Cobey; Peter Palese; Patrick C. Wilson. An Egg-Derived Sulfated N -Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines. mBio 2021, 12, e0083821 .

AMA Style

Jenna J. Guthmiller, Henry A. Utset, Carole Henry, Lei Li, Nai-Ying Zheng, Weina Sun, Marcos Costa Vieira, Seth Zost, Min Huang, Scott E. Hensley, Sarah Cobey, Peter Palese, Patrick C. Wilson. An Egg-Derived Sulfated N -Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines. mBio. 2021; 12 (3):e0083821.

Chicago/Turabian Style

Jenna J. Guthmiller; Henry A. Utset; Carole Henry; Lei Li; Nai-Ying Zheng; Weina Sun; Marcos Costa Vieira; Seth Zost; Min Huang; Scott E. Hensley; Sarah Cobey; Peter Palese; Patrick C. Wilson. 2021. "An Egg-Derived Sulfated N -Acetyllactosamine Glycan Is an Antigenic Decoy of Influenza Virus Vaccines." mBio 12, no. 3: e0083821.

Research article
Published: 02 June 2021 in Science Translational Medicine
Reads 0
Downloads 0

Broadly neutralizing antibodies are critical for protection against both drifted and shifted influenza viruses. Here, we reveal that first exposure to the 2009 pandemic H1N1 influenza virus recalls memory B cells that are specific to the conserved receptor-binding site (RBS) or lateral patch epitopes of the hemagglutinin (HA) head domain. Monoclonal antibodies (mAbs) generated against these epitopes are broadly neutralizing against H1N1 viruses spanning 40 years of viral evolution and provide potent protection in vivo. Lateral patch-targeting antibodies demonstrated near universal binding to H1 viruses, and RBS-binding antibodies commonly cross-reacted with H3N2 viruses and influenza B viruses. Lateral patch-targeting mAbs were restricted to expressing the variable heavy-chain gene VH3-23 with or without the variable kappa-chain gene VK1-33 and often had a Y-x-R motif within the heavy-chain complementarity determining region 3 to make key contacts with HA. Moreover, lateral patch antibodies that used both VH3-23 and VK1-33 maintained neutralizing capability with recent pH1N1 strains that acquired mutations near the lateral patch. RBS-binding mAbs used a diverse repertoire but targeted the RBS epitope similarly and made extensive contacts with the major antigenic site Sb. Together, our data indicate that RBS- and lateral patch-targeting clones are abundant within the human memory B cell pool, and universal vaccine strategies should aim to drive antibodies against both conserved head and stalk epitopes.

ACS Style

Jenna J. Guthmiller; Julianna Han; Lei Li; Alec W. Freyn; Sean T. H. Liu; Olivia Stovicek; Christopher T. Stamper; Haley L. Dugan; Micah E. Tepora; Henry A. Utset; Dalia J. Bitar; Natalie J. Hamel; Siriruk Changrob; Nai-Ying Zheng; Min Huang; Florian Krammer; Raffael Nachbagauer; Peter Palese; Andrew B. Ward; Patrick C. Wilson. First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes. Science Translational Medicine 2021, 13, eabg4535 .

AMA Style

Jenna J. Guthmiller, Julianna Han, Lei Li, Alec W. Freyn, Sean T. H. Liu, Olivia Stovicek, Christopher T. Stamper, Haley L. Dugan, Micah E. Tepora, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Siriruk Changrob, Nai-Ying Zheng, Min Huang, Florian Krammer, Raffael Nachbagauer, Peter Palese, Andrew B. Ward, Patrick C. Wilson. First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes. Science Translational Medicine. 2021; 13 (596):eabg4535.

Chicago/Turabian Style

Jenna J. Guthmiller; Julianna Han; Lei Li; Alec W. Freyn; Sean T. H. Liu; Olivia Stovicek; Christopher T. Stamper; Haley L. Dugan; Micah E. Tepora; Henry A. Utset; Dalia J. Bitar; Natalie J. Hamel; Siriruk Changrob; Nai-Ying Zheng; Min Huang; Florian Krammer; Raffael Nachbagauer; Peter Palese; Andrew B. Ward; Patrick C. Wilson. 2021. "First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes." Science Translational Medicine 13, no. 596: eabg4535.

Journal article
Published: 01 June 2021 in Immunity
Reads 0
Downloads 0

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.

ACS Style

Haley L. Dugan; Christopher T. Stamper; Lei Li; Siriruk Changrob; Nicholas W. Asby; Peter J. Halfmann; Nai-Ying Zheng; Min Huang; Dustin G. Shaw; Mari S. Cobb; Steven A. Erickson; Jenna J. Guthmiller; Olivia Stovicek; Jiaolong Wang; Emma S. Winkler; Maria Lucia Madariaga; Kumaran Shanmugarajah; Maud O. Jansen; Fatima Amanat; Isabelle Stewart; Henry A. Utset; Jun Huang; Christopher A. Nelson; Ya-Nan Dai; Paige D. Hall; Robert P. Jedrzejczak; Andrzej Joachimiak; Florian Krammer; Michael S. Diamond; Daved H. Fremont; Yoshihiro Kawaoka; Patrick C. Wilson. Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. Immunity 2021, 54, 1290 -1303.e7.

AMA Style

Haley L. Dugan, Christopher T. Stamper, Lei Li, Siriruk Changrob, Nicholas W. Asby, Peter J. Halfmann, Nai-Ying Zheng, Min Huang, Dustin G. Shaw, Mari S. Cobb, Steven A. Erickson, Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Emma S. Winkler, Maria Lucia Madariaga, Kumaran Shanmugarajah, Maud O. Jansen, Fatima Amanat, Isabelle Stewart, Henry A. Utset, Jun Huang, Christopher A. Nelson, Ya-Nan Dai, Paige D. Hall, Robert P. Jedrzejczak, Andrzej Joachimiak, Florian Krammer, Michael S. Diamond, Daved H. Fremont, Yoshihiro Kawaoka, Patrick C. Wilson. Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. Immunity. 2021; 54 (6):1290-1303.e7.

Chicago/Turabian Style

Haley L. Dugan; Christopher T. Stamper; Lei Li; Siriruk Changrob; Nicholas W. Asby; Peter J. Halfmann; Nai-Ying Zheng; Min Huang; Dustin G. Shaw; Mari S. Cobb; Steven A. Erickson; Jenna J. Guthmiller; Olivia Stovicek; Jiaolong Wang; Emma S. Winkler; Maria Lucia Madariaga; Kumaran Shanmugarajah; Maud O. Jansen; Fatima Amanat; Isabelle Stewart; Henry A. Utset; Jun Huang; Christopher A. Nelson; Ya-Nan Dai; Paige D. Hall; Robert P. Jedrzejczak; Andrzej Joachimiak; Florian Krammer; Michael S. Diamond; Daved H. Fremont; Yoshihiro Kawaoka; Patrick C. Wilson. 2021. "Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets." Immunity 54, no. 6: 1290-1303.e7.

Review
Published: 22 May 2021 in Viruses
Reads 0
Downloads 0

Antibodies are critical for providing protection against influenza virus infections. However, protective humoral immunity against influenza viruses is limited by the antigenic drift and shift of the major surface glycoproteins, hemagglutinin and neuraminidase. Importantly, people are exposed to influenza viruses throughout their life and tend to reuse memory B cells from prior exposure to generate antibodies against new variants. Despite this, people tend to recall memory B cells against constantly evolving variable epitopes or non-protective antigens, as opposed to recalling them against broadly neutralizing epitopes of hemagglutinin. In this review, we discuss the factors that impact the generation and recall of memory B cells against distinct viral antigens, as well as the immunological limitations preventing broadly neutralizing antibody responses. Lastly, we discuss how next-generation vaccine platforms can potentially overcome these obstacles to generate robust and long-lived protection against influenza A viruses.

ACS Style

Jenna Guthmiller; Henry Utset; Patrick Wilson. B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat. Viruses 2021, 13, 965 .

AMA Style

Jenna Guthmiller, Henry Utset, Patrick Wilson. B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat. Viruses. 2021; 13 (6):965.

Chicago/Turabian Style

Jenna Guthmiller; Henry Utset; Patrick Wilson. 2021. "B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat." Viruses 13, no. 6: 965.

Preprint content
Published: 29 April 2021
Reads 0
Downloads 0

Artificial mutagenesis and chimeric/mosaic protein engineering have laid the foundation for antigenic characterization1 and universal vaccine design2–4 for influenza viruses. However, many methods used for influenza research and vaccine development require sequence editing and protein expression, limiting their applicability and the progress of related research to specialists. Rapid tools allowing even novice influenza researchers to properly analyze and visualize influenza protein sequences with accurate nomenclature are needed to expand the research field. To address this need, we developed Librator, a system for analyzing and designing protein sequences of influenza virus Hemagglutinin (HA) and Neuraminidase (NA). With Librator’s graphical user interface (GUI) and built-in sequence editing functions, biologists can easily analyze influenza sequences and phylogenies, automatically port sequences to visualize structures, then readily mutate target residues and design sequences for antigen probes and chimeric/mosaic proteins efficiently and accurately. This system provides optimized fragment design for Gibson Assembly5 of HA and NA expression constructs based on peptide conservation of all historical HA and NA sequences, ensuring fragments are reusable and compatible, allowing for significant reagent savings. Use of Librator will significantly facilitate influenza research and vaccine antigen design.

ACS Style

Lei Li; Olivia Stovicek; Jenna J. Guthmiller; Siriruk Changrob; Yanbin Fu; Haley L. Dugan; Christopher T. Stamper; Nai-Ying Zheng; Min Huang; Patrick C. Wilson. Librator, a platform for optimized sequence editing, design, and expression of influenza virus proteins. 2021, 1 .

AMA Style

Lei Li, Olivia Stovicek, Jenna J. Guthmiller, Siriruk Changrob, Yanbin Fu, Haley L. Dugan, Christopher T. Stamper, Nai-Ying Zheng, Min Huang, Patrick C. Wilson. Librator, a platform for optimized sequence editing, design, and expression of influenza virus proteins. . 2021; ():1.

Chicago/Turabian Style

Lei Li; Olivia Stovicek; Jenna J. Guthmiller; Siriruk Changrob; Yanbin Fu; Haley L. Dugan; Christopher T. Stamper; Nai-Ying Zheng; Min Huang; Patrick C. Wilson. 2021. "Librator, a platform for optimized sequence editing, design, and expression of influenza virus proteins." , no. : 1.

Journal article
Published: 08 April 2021 in Journal of Experimental Medicine
Reads 0
Downloads 0

Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite–infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.

ACS Style

Rahul Vijay; Jenna J. Guthmiller; Alexandria J. Sturtz; Sequoia Crooks; Jordan T. Johnson; Lei Li; Linda Yu-Ling Lan; Rosemary L. Pope; Yani Chen; Kai J. Rogers; Nirmal Dutta; Jason E. Toombs; Mary E. Wilson; Patrick C. Wilson; Wendy Maury; Rolf A. Brekken; Noah S. Butler. Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation. Journal of Experimental Medicine 2021, 218, 1 .

AMA Style

Rahul Vijay, Jenna J. Guthmiller, Alexandria J. Sturtz, Sequoia Crooks, Jordan T. Johnson, Lei Li, Linda Yu-Ling Lan, Rosemary L. Pope, Yani Chen, Kai J. Rogers, Nirmal Dutta, Jason E. Toombs, Mary E. Wilson, Patrick C. Wilson, Wendy Maury, Rolf A. Brekken, Noah S. Butler. Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation. Journal of Experimental Medicine. 2021; 218 (6):1.

Chicago/Turabian Style

Rahul Vijay; Jenna J. Guthmiller; Alexandria J. Sturtz; Sequoia Crooks; Jordan T. Johnson; Lei Li; Linda Yu-Ling Lan; Rosemary L. Pope; Yani Chen; Kai J. Rogers; Nirmal Dutta; Jason E. Toombs; Mary E. Wilson; Patrick C. Wilson; Wendy Maury; Rolf A. Brekken; Noah S. Butler. 2021. "Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation." Journal of Experimental Medicine 218, no. 6: 1.

Preprint content
Published: 16 March 2021
Reads 0
Downloads 0

Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess differential glycosylation patterns than viruses circulating amongst humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived sulfated N-acetyllactosamine (LacNAc) that is an antigenic decoy. Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken derived cells, suggesting only egg-grown vaccines can induce anti-LacNAc antibodies. Notably, antibodies against the sulfated LacNAc utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and have simple heavy chain complementarity determining region 3. By analyzing a public dataset of influenza virus vaccine induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.

ACS Style

Jenna J. Guthmiller; Henry A. Utset; Carole Henry; Lei Li; Nai-Ying Zheng; Weina Sun; Marcos Costa Vieira; Seth Zost; Min Huang; Scott E. Hensley; Sarah Cobey; Peter Palese; Patrick C. Wilson. An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines. 2021, 1 .

AMA Style

Jenna J. Guthmiller, Henry A. Utset, Carole Henry, Lei Li, Nai-Ying Zheng, Weina Sun, Marcos Costa Vieira, Seth Zost, Min Huang, Scott E. Hensley, Sarah Cobey, Peter Palese, Patrick C. Wilson. An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines. . 2021; ():1.

Chicago/Turabian Style

Jenna J. Guthmiller; Henry A. Utset; Carole Henry; Lei Li; Nai-Ying Zheng; Weina Sun; Marcos Costa Vieira; Seth Zost; Min Huang; Scott E. Hensley; Sarah Cobey; Peter Palese; Patrick C. Wilson. 2021. "An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines." , no. : 1.

Preprint content
Published: 27 February 2021
Reads 0
Downloads 0

Influenza virus neuraminidase (NA) targeting antibodies are an independent correlate of protection against infection. Antibodies against the NA act by blocking enzymatic activity, preventing virus release and transmission. As we advance the development of improved influenza virus vaccines that incorporate standard amounts of NA antigen, it is important to identify the antigenic targets of human monoclonal antibodies (mAbs). Additionally, it is important to understand how escape from mAbs changes viral fitness. Here, we describe escape mutants generated by serial passage of A/Netherlands/602/2009 (H1N1) in the presence of human anti-N1 mAbs. We observed escape mutations on the N1 protein around the enzymatic site (S364N, N369T and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D and Q313K/R). We found that a majority of escape mutant viruses had increased fitness in vitro but not in vivo. This work increases our understanding of how human antibody responses target the N1 protein. Importance As improved influenza virus vaccines are being developed, the influenza virus neuraminidase (NA) is becoming an important new target for immune responses. By identifying novel epitopes of anti-NA antibodies, we can improve vaccine design. Additionally, characterizing changes in viruses containing mutations in these epitopes aids in identifying effects of NA antigenic drift.

ACS Style

Ericka Kirkpatrick Roubidoux; Meagan McMahon; Juan Manuel Carreño; Christina Capuano; Kaijun Jiang; Viviana Simon; Harm van Bakel; Patrick Wilson; Florian Krammer. Novel epitopes of human monoclonal antibodies targeting the influenza virus N1 neuraminidase. 2021, 1 .

AMA Style

Ericka Kirkpatrick Roubidoux, Meagan McMahon, Juan Manuel Carreño, Christina Capuano, Kaijun Jiang, Viviana Simon, Harm van Bakel, Patrick Wilson, Florian Krammer. Novel epitopes of human monoclonal antibodies targeting the influenza virus N1 neuraminidase. . 2021; ():1.

Chicago/Turabian Style

Ericka Kirkpatrick Roubidoux; Meagan McMahon; Juan Manuel Carreño; Christina Capuano; Kaijun Jiang; Viviana Simon; Harm van Bakel; Patrick Wilson; Florian Krammer. 2021. "Novel epitopes of human monoclonal antibodies targeting the influenza virus N1 neuraminidase." , no. : 1.

Preprint content
Published: 27 February 2021
Reads 0
Downloads 0

Summary Broadly neutralizing antibodies against influenza virus hemagglutinin (HA) have the potential to provide universal protection against influenza virus infections. Here, we report a distinct class of broadly neutralizing antibodies targeting an epitope toward the bottom of the HA stalk domain where HA is “anchored” to the viral membrane. Antibodies targeting this membrane-proximal anchor epitope utilized a highly restricted repertoire, which encode for two conserved motifs responsible for HA binding. Anchor targeting B cells were common in the human memory B cell repertoire across subjects, indicating pre-existing immunity against this epitope. Antibodies against the anchor epitope at both the serological and monoclonal antibody levels were potently induced in humans by a chimeric HA vaccine, a potential universal influenza virus vaccine. Altogether, this study reveals an underappreciated class of broadly neutralizing antibodies against H1-expressing viruses that can be robustly recalled by a candidate universal influenza virus vaccine.

ACS Style

Jenna J. Guthmiller; Julianna Han; Henry A. Utset; Lei Li; Linda Yu-Ling Lan; Carole Henry; Christopher T. Stamper; Olivia Stovicek; Lauren Gentles; Haley L. Dugan; Nai-Ying Zheng; Sara T. Richey; Micah E. Tepora; Dalia J. Bitar; Siriruk Changrob; Shirin Strohmeier; Min Huang; Adolfo García-Sastre; Raffael Nachbagauer; Peter Palese; Jesse D. Bloom; Florian Krammer; Lynda Coughlan; Andrew B. Ward; Patrick C. Wilson. A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin. 2021, 1 .

AMA Style

Jenna J. Guthmiller, Julianna Han, Henry A. Utset, Lei Li, Linda Yu-Ling Lan, Carole Henry, Christopher T. Stamper, Olivia Stovicek, Lauren Gentles, Haley L. Dugan, Nai-Ying Zheng, Sara T. Richey, Micah E. Tepora, Dalia J. Bitar, Siriruk Changrob, Shirin Strohmeier, Min Huang, Adolfo García-Sastre, Raffael Nachbagauer, Peter Palese, Jesse D. Bloom, Florian Krammer, Lynda Coughlan, Andrew B. Ward, Patrick C. Wilson. A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin. . 2021; ():1.

Chicago/Turabian Style

Jenna J. Guthmiller; Julianna Han; Henry A. Utset; Lei Li; Linda Yu-Ling Lan; Carole Henry; Christopher T. Stamper; Olivia Stovicek; Lauren Gentles; Haley L. Dugan; Nai-Ying Zheng; Sara T. Richey; Micah E. Tepora; Dalia J. Bitar; Siriruk Changrob; Shirin Strohmeier; Min Huang; Adolfo García-Sastre; Raffael Nachbagauer; Peter Palese; Jesse D. Bloom; Florian Krammer; Lynda Coughlan; Andrew B. Ward; Patrick C. Wilson. 2021. "A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin." , no. : 1.

Journal article
Published: 24 February 2021 in mSphere
Reads 0
Downloads 0

The influenza virus neuraminidase is an emerging target for universal influenza virus vaccines. However, in contrast to influenza virus hemagglutinin, we know little about antibody epitopes and antigenic sites on the neuraminidase. Characterizing and defining these sites is aiding vaccine development and helping to understand antigenic drift of NA.

ACS Style

Ericka Kirkpatrick Roubidoux; Meagan McMahon; Juan Manuel Carreño; Christina Capuano; Kaijun Jiang; Viviana Simon; Harm van Bakel; Patrick Wilson; Florian Krammer. Identification and Characterization of Novel Antibody Epitopes on the N2 Neuraminidase. mSphere 2021, 6, 1 .

AMA Style

Ericka Kirkpatrick Roubidoux, Meagan McMahon, Juan Manuel Carreño, Christina Capuano, Kaijun Jiang, Viviana Simon, Harm van Bakel, Patrick Wilson, Florian Krammer. Identification and Characterization of Novel Antibody Epitopes on the N2 Neuraminidase. mSphere. 2021; 6 (1):1.

Chicago/Turabian Style

Ericka Kirkpatrick Roubidoux; Meagan McMahon; Juan Manuel Carreño; Christina Capuano; Kaijun Jiang; Viviana Simon; Harm van Bakel; Patrick Wilson; Florian Krammer. 2021. "Identification and Characterization of Novel Antibody Epitopes on the N2 Neuraminidase." mSphere 6, no. 1: 1.

Article
Published: 16 February 2021 in mBio
Reads 0
Downloads 0

Current seasonal influenza virus vaccines target regions of the hemagglutinin (HA) head domain that undergo constant antigenic change, forcing the painstaking annual reformulation of vaccines. The development of broadly protective or universal influenza virus vaccines that induce cross-reactive, protective immune responses could circumvent the need to reformulate current seasonal vaccines. Many of these vaccine candidates target the HA stalk domain, which displays epitopes conserved within and across influenza virus subtypes, including those with pandemic potential. While HA head-mediated antigenic drift is well understood, the potential for antigenic drift in the stalk domain is understudied. Using a panel of HA stalk-specific monoclonal antibodies (MAbs), we applied selection pressure to the stalk domain of A/Netherlands/602/2009 (pdmH1N1) to determine fitness and phenotypes of escape mutant viruses (EMVs). We found that HA stalk MAbs with lower cross-reactivity caused single HA stalk escape mutations, whereas MAbs with broader cross-reactivity forced multiple mutations in the HA. Each escape mutant virus greatly decreased mAb neutralizing activity, but escape mutations did not always ablate MAb binding or Fc-Fc receptor-based effector functions. Escape mutant viruses were not attenuated in vitro but showed attenuation in an in vivo mouse model. Importantly, mice vaccinated with a chimeric HA universal vaccine candidate were protected from lethal challenge with EMVs despite these challenge viruses containing escape mutations in the stalk domain. Our study indicates that while the HA stalk domain can mutate under strong MAb selection pressure, mutant viruses may have attenuated phenotypes and do not evade a polyclonal, stalk-based vaccine-induced response. IMPORTANCE Broadly protective or universal influenza virus vaccines target viral epitopes that appear to be conserved. However, it is unclear whether the virus will be able to escape once immunological pressure is applied to these epitopes through vaccination of large proportions of the population. Studies that investigate the fitness and antigenic characteristics of viruses that escape immunological pressure on these conserved epitopes are therefore urgently needed.

ACS Style

Ericka Kirkpatrick Roubidoux; Juan Manuel Carreño; Meagan McMahon; Kaijun Jiang; Harm van Bakel; Patrick Wilson; Florian Krammer. Mutations in the Hemagglutinin Stalk Domain Do Not Permit Escape from a Protective, Stalk-Based Vaccine-Induced Immune Response in the Mouse Model. mBio 2021, 12, 1 .

AMA Style

Ericka Kirkpatrick Roubidoux, Juan Manuel Carreño, Meagan McMahon, Kaijun Jiang, Harm van Bakel, Patrick Wilson, Florian Krammer. Mutations in the Hemagglutinin Stalk Domain Do Not Permit Escape from a Protective, Stalk-Based Vaccine-Induced Immune Response in the Mouse Model. mBio. 2021; 12 (1):1.

Chicago/Turabian Style

Ericka Kirkpatrick Roubidoux; Juan Manuel Carreño; Meagan McMahon; Kaijun Jiang; Harm van Bakel; Patrick Wilson; Florian Krammer. 2021. "Mutations in the Hemagglutinin Stalk Domain Do Not Permit Escape from a Protective, Stalk-Based Vaccine-Induced Immune Response in the Mouse Model." mBio 12, no. 1: 1.

Article
Published: 19 January 2021 in mBio
Reads 0
Downloads 0

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike. IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

ACS Style

Jenna J. Guthmiller; Olivia Stovicek; Jiaolong Wang; Siriruk Changrob; Lei Li; Peter Halfmann; Nai-Ying Zheng; Henry Utset; Christopher T. Stamper; Haley L. Dugan; William D. Miller; Min Huang; Ya-Nan Dai; Christopher A. Nelson; Paige D. Hall; Maud Jansen; Kumaran Shanmugarajah; Jessica S. Donington; Florian Krammer; Daved H. Fremont; Andrzej Joachimiak; Yoshihiro Kawaoka; Vera Tesic; Maria Lucia Madariaga; Patrick C. Wilson. SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike. mBio 2021, 12, 1 .

AMA Style

Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Siriruk Changrob, Lei Li, Peter Halfmann, Nai-Ying Zheng, Henry Utset, Christopher T. Stamper, Haley L. Dugan, William D. Miller, Min Huang, Ya-Nan Dai, Christopher A. Nelson, Paige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. Fremont, Andrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson. SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike. mBio. 2021; 12 (1):1.

Chicago/Turabian Style

Jenna J. Guthmiller; Olivia Stovicek; Jiaolong Wang; Siriruk Changrob; Lei Li; Peter Halfmann; Nai-Ying Zheng; Henry Utset; Christopher T. Stamper; Haley L. Dugan; William D. Miller; Min Huang; Ya-Nan Dai; Christopher A. Nelson; Paige D. Hall; Maud Jansen; Kumaran Shanmugarajah; Jessica S. Donington; Florian Krammer; Daved H. Fremont; Andrzej Joachimiak; Yoshihiro Kawaoka; Vera Tesic; Maria Lucia Madariaga; Patrick C. Wilson. 2021. "SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike." mBio 12, no. 1: 1.

Article commentary
Published: 10 December 2020 in Science
Reads 0
Downloads 0
ACS Style

Jenna J. Guthmiller; Patrick C. Wilson. Remembering seasonal coronaviruses. Science 2020, 370, 1272 -1273.

AMA Style

Jenna J. Guthmiller, Patrick C. Wilson. Remembering seasonal coronaviruses. Science. 2020; 370 (6522):1272-1273.

Chicago/Turabian Style

Jenna J. Guthmiller; Patrick C. Wilson. 2020. "Remembering seasonal coronaviruses." Science 370, no. 6522: 1272-1273.

Research article
Published: 09 December 2020 in Science Translational Medicine
Reads 0
Downloads 0

Humans are repeatedly exposed to variants of influenza virus throughout their lifetime. As a result, preexisting influenza-specific memory B cells can dominate the response after infection or vaccination. Memory B cells recalled by adulthood exposure are largely reactive to conserved viral epitopes present in childhood strains, posing unclear consequences on the ability of B cells to adapt to and neutralize newly emerged strains. We sought to investigate the impact of preexisting immunity on generation of protective antibody responses to conserved viral epitopes upon influenza virus infection and vaccination in humans. We accomplished this by characterizing monoclonal antibodies (mAbs) from plasmablasts, which are predominantly derived from preexisting memory B cells. We found that, whereas some influenza infection–induced mAbs bound conserved and neutralizing epitopes on the hemagglutinin (HA) stalk domain or neuraminidase, most of the mAbs elicited by infection targeted non-neutralizing epitopes on nucleoprotein and other unknown antigens. Furthermore, most infection-induced mAbs had equal or stronger affinity to childhood strains, indicating recall of memory B cells from childhood exposures. Vaccination-induced mAbs were similarly induced from past exposures and exhibited substantial breadth of viral binding, although, in contrast to infection-induced mAbs, they targeted neutralizing HA head epitopes. Last, cocktails of infection-induced mAbs displayed reduced protective ability in mice compared to vaccination-induced mAbs. These findings reveal that both preexisting immunity and exposure type shape protective antibody responses to conserved influenza virus epitopes in humans. Natural infection largely recalls cross-reactive memory B cells against non-neutralizing epitopes, whereas vaccination harnesses preexisting immunity to target protective HA epitopes.

ACS Style

Haley L. Dugan; Jenna J. Guthmiller; Philip Arevalo; Min Huang; Yao-Qing Chen; Karlynn E. Neu; Carole Henry; Nai-Ying Zheng; Linda Yu-Ling Lan; Micah E. Tepora; Olivia Stovicek; Dalia Bitar; Anna-Karin E. Palm; Christopher T. Stamper; Siriruk Changrob; Henry A. Utset; Lynda Coughlan; Florian Krammer; Sarah Cobey; Patrick C. Wilson. Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans. Science Translational Medicine 2020, 12, eabd3601 .

AMA Style

Haley L. Dugan, Jenna J. Guthmiller, Philip Arevalo, Min Huang, Yao-Qing Chen, Karlynn E. Neu, Carole Henry, Nai-Ying Zheng, Linda Yu-Ling Lan, Micah E. Tepora, Olivia Stovicek, Dalia Bitar, Anna-Karin E. Palm, Christopher T. Stamper, Siriruk Changrob, Henry A. Utset, Lynda Coughlan, Florian Krammer, Sarah Cobey, Patrick C. Wilson. Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans. Science Translational Medicine. 2020; 12 (573):eabd3601.

Chicago/Turabian Style

Haley L. Dugan; Jenna J. Guthmiller; Philip Arevalo; Min Huang; Yao-Qing Chen; Karlynn E. Neu; Carole Henry; Nai-Ying Zheng; Linda Yu-Ling Lan; Micah E. Tepora; Olivia Stovicek; Dalia Bitar; Anna-Karin E. Palm; Christopher T. Stamper; Siriruk Changrob; Henry A. Utset; Lynda Coughlan; Florian Krammer; Sarah Cobey; Patrick C. Wilson. 2020. "Preexisting immunity shapes distinct antibody landscapes after influenza virus infection and vaccination in humans." Science Translational Medicine 12, no. 573: eabd3601.

Journal article
Published: 07 December 2020 in Nature Medicine
Reads 0
Downloads 0

Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

ACS Style

Raffael Nachbagauer; Jodi Feser; Abdollah Naficy; David I. Bernstein; Jeffrey Guptill; Emmanuel B. Walter; Franceso Berlanda-Scorza; Daniel Stadlbauer; Patrick C. Wilson; Teresa Aydillo; Mohammad Amin Behzadi; Disha Bhavsar; Carly Bliss; Christina Capuano; Juan Manuel Carreño; Veronika Chromikova; Carine Claeys; Lynda Coughlan; Alec W. Freyn; Christopher Gast; Andres Javier; Kaijun Jiang; Chiara Mariottini; Meagan McMahon; Monica McNeal; Alicia Solórzano; Shirin Strohmeier; Weina Sun; Marie Van Der Wielen; Bruce L. Innis; Adolfo García-Sastre; Peter Palese; Florian Krammer. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nature Medicine 2020, 27, 106 -114.

AMA Style

Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I. Bernstein, Jeffrey Guptill, Emmanuel B. Walter, Franceso Berlanda-Scorza, Daniel Stadlbauer, Patrick C. Wilson, Teresa Aydillo, Mohammad Amin Behzadi, Disha Bhavsar, Carly Bliss, Christina Capuano, Juan Manuel Carreño, Veronika Chromikova, Carine Claeys, Lynda Coughlan, Alec W. Freyn, Christopher Gast, Andres Javier, Kaijun Jiang, Chiara Mariottini, Meagan McMahon, Monica McNeal, Alicia Solórzano, Shirin Strohmeier, Weina Sun, Marie Van Der Wielen, Bruce L. Innis, Adolfo García-Sastre, Peter Palese, Florian Krammer. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nature Medicine. 2020; 27 (1):106-114.

Chicago/Turabian Style

Raffael Nachbagauer; Jodi Feser; Abdollah Naficy; David I. Bernstein; Jeffrey Guptill; Emmanuel B. Walter; Franceso Berlanda-Scorza; Daniel Stadlbauer; Patrick C. Wilson; Teresa Aydillo; Mohammad Amin Behzadi; Disha Bhavsar; Carly Bliss; Christina Capuano; Juan Manuel Carreño; Veronika Chromikova; Carine Claeys; Lynda Coughlan; Alec W. Freyn; Christopher Gast; Andres Javier; Kaijun Jiang; Chiara Mariottini; Meagan McMahon; Monica McNeal; Alicia Solórzano; Shirin Strohmeier; Weina Sun; Marie Van Der Wielen; Bruce L. Innis; Adolfo García-Sastre; Peter Palese; Florian Krammer. 2020. "A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial." Nature Medicine 27, no. 1: 106-114.

Journal article
Published: 09 November 2020 in Nature Immunology
Reads 0
Downloads 0

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1. COVID-19 is often characterized by a hyperinflammatory syndrome. Wang and colleagues show that low levels of IgG fucosylation enhance interactions with activating Fcγ receptors, boosting the inflammatory cytokines associated with severe COVID-19.

ACS Style

Saborni Chakraborty; Joseph Gonzalez; Karlie Edwards; Vamsee Mallajosyula; Anthony S. Buzzanco; Robert Sherwood; Cindy Buffone; Nimish Kathale; Susan Providenza; Markus M. Xie; Jason R. Andrews; Catherine A. Blish; Upinder Singh; Haley Dugan; Patrick C. Wilson; Tho D. Pham; Scott D. Boyd; Kari C. Nadeau; Benjamin A. Pinsky; Sheng Zhang; Matthew J. Memoli; Jeffery K. Taubenberger; Tasha Morales; Jeffrey M. Schapiro; Gene S. Tan; Prasanna Jagannathan; Taia T. Wang. Proinflammatory IgG Fc structures in patients with severe COVID-19. Nature Immunology 2020, 22, 67 -73.

AMA Style

Saborni Chakraborty, Joseph Gonzalez, Karlie Edwards, Vamsee Mallajosyula, Anthony S. Buzzanco, Robert Sherwood, Cindy Buffone, Nimish Kathale, Susan Providenza, Markus M. Xie, Jason R. Andrews, Catherine A. Blish, Upinder Singh, Haley Dugan, Patrick C. Wilson, Tho D. Pham, Scott D. Boyd, Kari C. Nadeau, Benjamin A. Pinsky, Sheng Zhang, Matthew J. Memoli, Jeffery K. Taubenberger, Tasha Morales, Jeffrey M. Schapiro, Gene S. Tan, Prasanna Jagannathan, Taia T. Wang. Proinflammatory IgG Fc structures in patients with severe COVID-19. Nature Immunology. 2020; 22 (1):67-73.

Chicago/Turabian Style

Saborni Chakraborty; Joseph Gonzalez; Karlie Edwards; Vamsee Mallajosyula; Anthony S. Buzzanco; Robert Sherwood; Cindy Buffone; Nimish Kathale; Susan Providenza; Markus M. Xie; Jason R. Andrews; Catherine A. Blish; Upinder Singh; Haley Dugan; Patrick C. Wilson; Tho D. Pham; Scott D. Boyd; Kari C. Nadeau; Benjamin A. Pinsky; Sheng Zhang; Matthew J. Memoli; Jeffery K. Taubenberger; Tasha Morales; Jeffrey M. Schapiro; Gene S. Tan; Prasanna Jagannathan; Taia T. Wang. 2020. "Proinflammatory IgG Fc structures in patients with severe COVID-19." Nature Immunology 22, no. 1: 67-73.

Journal article
Published: 22 October 2020 in Immunity
Reads 0
Downloads 0

Summary Polyreactivity is the ability of a single antibody to bind to multiple molecularly distinct antigens and is a common feature of antibodies induced upon pathogen exposure. However, little is known about the role of polyreactivity during anti-influenza virus antibody responses. By analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we found mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes were polyreactive. Polyreactive mAbs were preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augmented mAb viral binding strength by increasing antibody flexibility, allowing for adaption to imperfectly conserved epitopes. Lastly, we found affinity-matured polyreactive B cells were typically derived from germline polyreactive B cells that were preferentially selected to participate in B cell responses over time. Together, our data reveal that polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.

ACS Style

Jenna J. Guthmiller; Linda Yu-Ling Lan; Monica L. Fernández-Quintero; Julianna Han; Henry A. Utset; Dalia J. Bitar; Natalie J. Hamel; Olivia Stovicek; Lei Li; Micah Tepora; Carole Henry; Karlynn E. Neu; Haley L. Dugan; Marta T. Borowska; Yao-Qing Chen; Sean T.H. Liu; Christopher T. Stamper; Nai-Ying Zheng; Min Huang; Anna-Karin E. Palm; Adolfo García-Sastre; Raffael Nachbagauer; Peter Palese; Lynda Coughlan; Florian Krammer; Andrew B. Ward; Klaus R. Liedl; Patrick C. Wilson. Polyreactive Broadly Neutralizing B cells Are Selected to Provide Defense against Pandemic Threat Influenza Viruses. Immunity 2020, 53, 1230 -1244.e5.

AMA Style

Jenna J. Guthmiller, Linda Yu-Ling Lan, Monica L. Fernández-Quintero, Julianna Han, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Olivia Stovicek, Lei Li, Micah Tepora, Carole Henry, Karlynn E. Neu, Haley L. Dugan, Marta T. Borowska, Yao-Qing Chen, Sean T.H. Liu, Christopher T. Stamper, Nai-Ying Zheng, Min Huang, Anna-Karin E. Palm, Adolfo García-Sastre, Raffael Nachbagauer, Peter Palese, Lynda Coughlan, Florian Krammer, Andrew B. Ward, Klaus R. Liedl, Patrick C. Wilson. Polyreactive Broadly Neutralizing B cells Are Selected to Provide Defense against Pandemic Threat Influenza Viruses. Immunity. 2020; 53 (6):1230-1244.e5.

Chicago/Turabian Style

Jenna J. Guthmiller; Linda Yu-Ling Lan; Monica L. Fernández-Quintero; Julianna Han; Henry A. Utset; Dalia J. Bitar; Natalie J. Hamel; Olivia Stovicek; Lei Li; Micah Tepora; Carole Henry; Karlynn E. Neu; Haley L. Dugan; Marta T. Borowska; Yao-Qing Chen; Sean T.H. Liu; Christopher T. Stamper; Nai-Ying Zheng; Min Huang; Anna-Karin E. Palm; Adolfo García-Sastre; Raffael Nachbagauer; Peter Palese; Lynda Coughlan; Florian Krammer; Andrew B. Ward; Klaus R. Liedl; Patrick C. Wilson. 2020. "Polyreactive Broadly Neutralizing B cells Are Selected to Provide Defense against Pandemic Threat Influenza Viruses." Immunity 53, no. 6: 1230-1244.e5.