Review
Immunology
Stephen R. Walsh, Michael S. Seaman
Summary: The current clinical studies are actively exploring the use of bnAbs as passive immunization strategies to prevent HIV-1 infection. Recent trials have shown that bnAbs can provide protection against HIV-1 infection in humans, but there are still significant barriers to overcome.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sai Luo, Changbin Jing, Adam Yongxin Ye, Sven Kratochvil, Christopher A. Cottrell, Ja-Hyun Koo, Aimee Chapdelaine Williams, Lucas Vieira Francisco, Himanshu Batra, Edward Lamperti, Oleksandr Kalyuzhniy, Yuxiang Zhang, Alessandro Barbieri, John P. Manis, Barton F. Haynes, William R. Schief, Facundo D. Batista, Ming Tian, Frederick W. Alt
Summary: Antibody heavy chain and light chain variable region exons are assembled through V(D)J recombination. HIV-1 vaccine strategies aim to induce broadly neutralizing antibodies against HIV-1. Using rearranging mouse models can help better evaluate vaccine effectiveness.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, Kunxue Hong
Summary: This study analyzed the evolutionary characteristics and neutralization sensitivity of viruses in HIV-1 subtype B infected patients, revealing that two virus clusters adopted different escape mechanisms under different immune pressures.
Article
Multidisciplinary Sciences
Matthijs Meijers, Kanika Vanshylla, Henning Gruell, Florian Klein, Michael Laessig
Summary: Broadly neutralizing antibodies show promise in treating and preventing HIV-1 infections, but the virus often evolves resistance. A fitness model based on in vivo data accurately predicts the dynamics of HIV-1 escape during antibody treatment, highlighting an evolutionary trade-off between antibody resistance and its collateral cost.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Eleonora Melzi, Jordan R. Willis, Krystal M. Ma, Ying-Cing Lin, Sven Kratochvil, Zachary T. Berndsen, Elise A. Landais, Oleksandr Kalyuzhniy, Usha Nair, John Warner, Jon M. Steichen, Anton Kalyuzhniy, Amber Le, Simone Pecetta, Manfredo Perez, Kathrin Kirsch, Stephanie R. Weldon, Samantha Falcone, Sunny Himansu, Andrea Carfi, Devin Sok, Andrew B. Ward, William R. Schief, Facundo D. Batista
Summary: Eliciting broadly neutralizing antibodies is essential for HIV vaccine design, and research has shown that high-affinity ApexGT immunogens are crucial for activating and selecting mature bnAb mutations. Additionally, mRNA-LNP is a suitable approach for significantly improving B cell responses.
Article
Biochemistry & Molecular Biology
Dai Zhang, Zhen Liu, Wei Wang, Ming-Xin Chen, Jia-Li Hou, Zhen Zhang, Wei-Hong Ren, Li Ren, Yan-Ling Hao
Summary: Through studying the antibody resistance of HIV-1 variants, we identified a new VRC01-like antibody called DRVIA7, which has broad neutralization activity. Site-directed mutagenesis and amino acid swapping showed that specific mutations can enhance the neutralization sensitivity to VRC01. Additionally, we found that certain residues play a vital role in binding with both VRC01 and A7 lineage antibodies.
MOLECULAR IMMUNOLOGY
(2022)
Review
Immunology
Denise C. C. Hsu, John W. W. Mellors, Sandhya Vasan
Summary: Broadly neutralizing antibodies (bnAbs) targeting the HIV-1 envelope glycoprotein are promising strategies for HIV-1 prevention, treatment, and remission. Research on the combination of bnAbs with different resistance profiles is essential to address concerns about HIV-1 resistance. Additionally, studies on bnAbs in preclinical models and clinical trials are important to optimize therapeutic outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Peng Zhang, Alice L. Kwon, Christina Guzzo, Qingbo Liu, Hana Schmeisser, Huiyi Miao, Yin Lin, Raffaello Cimbro, Jinghe Huang, Mark Connors, Stephen D. Schmidt, Michael A. Dolan, Anthony A. Armstrong, Paolo Lusso
Summary: Research has identified key hydrophobic constraints at the apex of the HIV-1 envelope trimer that act as global stabilizers of the spike configuration. Mutations at the apex can increase sensitivity to certain neutralizing antibodies while decreasing sensitivity to others. Sera from chronically HIV-infected patients show enhanced potency in neutralizing open mutants compared to wild-type virus, indicating a significant target of antibodies on concealed epitopes.
Article
Multidisciplinary Sciences
David J. Leggat, Kristen W. Cohen, Jordan R. Willis, William J. Fulp, Allan C. deCamp, Oleksandr Kalyuzhniy, Christopher A. Cottrell, Sergey Menis, Greg Finak, Lamar Ballweber-Fleming, Abhinaya Srikanth, Jason R. Plyler, Torben Schiffner, Alessia Liguori, Farhad Rahaman, Angela Lombardo, Vincent Philiponis, Rachael E. Whaley, Aaron Seese, Joshua Brand, Alexis M. Ruppel, Wesley Hoyland, Nicole L. Yates, LaTonya D. Williams, Kelli Greene, Hongmei Gao, Celia R. Mahoney, Martin M. Corcoran, Alberto Cagigi, Alison Taylor, David M. Brown, David R. Ambrozak, Troy Sincomb, Xiaozhen Hu, Ryan Tingle, Erik Georgeson, Saman Eskandarzadeh, Nushin Alavi, Danny Lu, Tina-Marie Mullen, Michael Kubitz, Bettina Groschel, Janine Maenza, Orpheus Kolokythas, Nadia Khati, Jeffrey Bethony, Shane Crotty, Mario Roederer, Gunilla B. Karlsson Hedestam, Georgia D. Tomaras, David Montefiori, David Diemert, Richard A. Koup, Dagna S. Laufer, M. Juliana McElrath, Adrian B. McDermott, William R. Schief
Summary: This study found that an HIV vaccine can prime the production of precursor B cells for broadly neutralizing antibodies (bnAbs), potentially opening up possibilities for inducing these antibodies. The results provide theoretical support for the development of vaccine boosting regimens to induce bnAbs and encourage the application of this strategy to other targets in HIV and other pathogens.
Article
Immunology
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates, James C. Paulson, Max Crispin, Andrew B. Ward, William R. Schief
Summary: Researchers have identified two important antibodies for HIV vaccine development through deep sequencing of human antibody heavy-chain sequences.
Article
Virology
Priyanka Gadam Rao, Gregory S. Lambert, Chitra Upadhyay
Summary: This study aimed to identify exposed/occluded Env epitopes on HIV-1 particles and investigate the mechanisms contributing to their masking. The researchers found that only select epitopes are accessible on virus particles, while others are masked. These masked epitopes can become accessible through pre-binding of specific antibodies or lectin-glycan interactions.
JOURNAL OF VIROLOGY
(2023)
Article
Biology
Colin LaMont, Jakub Otwinowski, Kanika Vanshylla, Henning Gruell, Florian Klein, Armita Nourmohammad
Summary: This study proposes a computational approach based on the population genetics of HIV escape to predict the efficacy of bNAb therapy. By using high-throughput HIV sequence data from bNAb-naive patients to parametrize HIV escape, the distribution of rebound times in three clinical trials is predicted. It is shown that a combination of three bNAbs is necessary to effectively suppress viral escape.
Article
Biochemistry & Molecular Biology
Oluwarotimi Omorodion, Ian A. Wilson
Summary: This study investigates the cysteinylation in a lineage of broadly neutralizing antibodies targeting the N332-glycan supersite on the surface envelope glycoprotein (Env) of HIV-1. Through chromatography and mass spectrometry, subpopulations of cysteinylated and noncysteinylated antibodies expressed in mammalian cells were characterized. The crystal structures of two PCDN antibodies represent the first structures of a cysteinylated antibody and show that the cysteinylation in this case is located in CDRH3. Biophysical studies indicate that cysteinylation of these HIV-1 antibodies does not interfere with antigen binding, which differs from other cysteinylated antibodies.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nuno Taveira, Ines Figueiredo, Rita Calado, Francisco Martin, Ines Bartolo, Jose M. Marcelino, Pedro Borrego, Fernando Cardoso, Helena Barroso
Summary: Developing immunogens that can elicit broadly neutralizing antibodies (bNAbs) is crucial for the development of an effective HIV vaccine. In this study, a prime-boost vaccination strategy using vaccinia virus expressing the gp120 envelope glycoprotein of HIV-2 and a polypeptide comprising specific regions of the envelope glycoprotein was shown to elicit bNAbs against both HIV-1 and HIV-2. The findings suggest that a chimeric envelope glycoprotein containing specific regions from both viruses could be a potential vaccine immunogen to target neutralizing epitopes in both HIV-1 and HIV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Simone I. I. Richardson, Frances Ayres, Nelia P. P. Manamela, Brent Oosthuysen, Zanele Makhado, Bronwen E. E. Lambson, Lynn Morris, Penny L. L. Moore
Summary: The study revealed that IgG3 bNAbs demonstrate stronger protective ability and phagocytosis against HIV infection, especially against certain specific HIV strains, indicating that altering the constant region of antibodies may enhance their neutralizing and Fc effector activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Roos S. G. Sablerolles, Wim J. R. Rietdijk, Abraham Goorhuis, Douwe F. Postma, Leo G. Visser, Katharina S. Schmitz, Daryl Geers, Susanne Bogers, Eva van Haren, Marion P. G. Koopmans, Virgil A. S. H. Dalm, Neeltje A. Kootstra, Anke L. W. Huckriede, Renate Akkerman, Martin Beukema, Melvin Lafeber, Debbie van Baarle, Rory D. de Vries, P. Hugo M. van der Kuy, Corine H. GeurtsvanKessel
Summary: This study found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells remained detectable 5 months after boosting with Ad26.COV2.S vaccine, although there was a decline in antibody levels and limited cross-reactivity with Omicron BA.1.
CLINICAL INFECTIOUS DISEASES
(2023)
Letter
Gastroenterology & Hepatology
Vladimir Loukachov, Karel van Dort, Robin Erken, Henk W. Reesink, Neeltje Kootstra
Article
Multidisciplinary Sciences
Jennifer Cable, Jie Sun, In Su Cheon, Andrew E. Vaughan, Italo A. Castro, Sydney R. Stein, Carolina B. Lopez, Katelyn M. Gostic, Peter J. M. Openshaw, Ali H. Ellebedy, Andreas Wack, Edward Hutchinson, Mallory M. Thomas, Ryan A. Langlois, Daniel Lingwood, Steven F. Baker, Melanie Folkins, Ellen F. Foxman, Andrew B. Ward, Martin Schwemmle, Alistair B. Russell, Christopher Chiu, Ketaki Ganti, Kanta Subbarao, Timothy P. Sheahan, Pablo Penaloza-MacMaster, Taylor Eddens
Summary: Respiratory viruses, including influenza, RSV, and SARS-CoV-2, pose a significant threat to global public health. Researchers at the Keystone symposium Respiratory Viruses: New Frontiers presented novel insights into viral biology and virus-host interactions, aiming to understand disease mechanisms and develop effective treatment and prevention strategies that are durable and broad.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Immunology
Emma F. Avery, Julia N. Kleynhans, Bruno Ledergerber, Isabella C. Schoepf, Christian W. Thorball, Neeltje A. Kootstra, Peter Reiss, Lene Ryom, Dominique L. Braun, Maria C. Thurnheer, Catia Marzolini, Marco Seneghini, Enos Bernasconi, Matthias Cavassini, Helene Buvelot, Roger D. Kouyos, Jacques Fellay, Huldrych F. Guenthard, Philip E. Tarr
Summary: In Switzerland, leukocyte count is independently associated with coronary artery disease (CAD) events in people with HIV (PWH), even after adjusting for traditional and HIV-related risk factors.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Maddy L. Newby, Carl A. Fogarty, Joel D. Allen, John Butler, Elisa Fadda, Max Crispin
Summary: The emergence of SARS-CoV-2 variants affects the effectiveness of existing immunity. Understanding the structure of the viral spike helps determine the impact of mutations on the antigenic surface. One type of mutation affects glycosylation attachment sites, which can influence the antigenic structure beyond the immediate attachment site. This study compares the glycosylation of different variants and investigates the effects of specific glycan sites on the spike protein.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Obstetrics & Gynecology
Malavika Prabhu, Yawei J. Yang, Carrie D. Johnston, Elisabeth A. Murphy, Thomas J. Ketas, Randy Diaz-Tapia, Magdalena Jurkiewicz, Sabrina Racine-Brzostek, Iman Mohammed, Ashley C. Sukhu, Sunidhi Singh, Kimberly Forlenza, Sonali Iyer, Jim Yee, Dorothy Eng, Kristen Marks, Zhen Zhao, Per Johan Klasse, Sallie Permar, John P. Moore, Laura E. Riley
Summary: This study aimed to investigate the immune response to SARS-CoV-2 vaccination in pregnant individuals and compare it with nonpregnant individuals. The results showed that the immune response in pregnant individuals was independent of gestational age and that the immunoglobulin G response was comparable between pregnant and nonpregnant individuals. However, there were differential responses for immunoglobulin M and immunoglobulin A, which require further investigation.
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
(2023)
Article
Multidisciplinary Sciences
Yi-Nan Zhang, Jennifer Paynter, Aleksandar Antanasijevic, Joel D. Allen, Mor Eldad, Yi-Zong Lee, Jeffrey Copps, Maddy L. Newby, Linling He, Deborah Chavez, Pat Frost, Anna Goodroe, John Dutton, Robert Lanford, Christopher Chen, Ian A. Wilson, Max Crispin, Andrew B. Ward, Jiang Zhu
Summary: The authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Gregory M. Martin, Monica L. Fernandez-Quintero, Wen-Hsin Lee, Tossapol Pholcharee, Lisa Eshun-Wilson, Klaus R. Liedl, Marie Pancera, Robert A. Seder, Ian A. Wilson, Andrew B. Ward
Summary: A cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP reveals that L9 Fab binds multivalently to the minor (NPNV) repeat domain, stabilized by affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations highlight the critical role of the L9 light chain in the integrity of the homotypic interface, influencing PfCSP affinity and protective efficacy. These findings uncover the molecular mechanism of L9's unique NPNV selectivity and underscore the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Hailee R. Perrett, Philip J. M. Brouwer, Jonathan Hurtado, Maddy L. Newby, Lin Liu, Helena Mueller-Kraeuter, Sarah Mueller Aguirre, Judith A. Burger, Joey H. Bouhuijs, Grace Gibson, Terrence Messmer, John S. Schieffelin, Aleksandar Antanasijevic, Geert-Jan Boons, Thomas Strecker, Max Crispin, Rogier W. Sanders, Bryan Briney, Andrew B. Ward
Summary: This study presents the development and characterization of prefusion-stabilized GPCs from different lineages of Lassa virus. It reveals structural conservation and neutralization mechanisms of antibodies, and identifies a potential neutralizing antibody, providing important molecular information for vaccine design against Lassa fever.
Article
Cell Biology
Joel D. Allen, Dylan P. Ivory, Sophie Ge Song, Wan-Ting He, Tazio Capozzola, Peter Yong, Dennis R. Burton, Raiees Andrabi, Max Crispin
Summary: Animal reservoirs of sarbecoviruses pose a risk of pandemics, so there is a need for pan-coronavirus vaccines. The glycan shields of coronaviruses vary, with the S2 domain having a lower glycan shield density. This makes the S2 domain a potential target for vaccine design.
Article
Cell Biology
Tom G. Caniels, Max Medina-Ramirez, Jinsong Zhang, Anita Sarkar, Sonu Kumar, Alex LaBranche, Ronald Derking, Joel D. Allen, Jonne L. Snitselaar, Joan Capella-Pujol, Ivan del Moral Sanchez, Anila Yasmeen, Marilyn Diaz, Yoann Aldon, Tom P. L. Bijl, Sravani Venkatayogi, Joshua S. Martin Beem, Amanda Newman, Chuancang Jiang, Wen-Hsin Lee, Maarten Pater, Judith A. Burger, Marielle J. van Breemen, Steven W. de Taeye, Kimmo Rantalainen, Celia LaBranche, Kevin O. Saunders, David Montefiori, Gabriel Ozorowski, Andrew B. Ward, Max Crispin, John P. Moore, Per Johan Klasse, Barton F. Haynes, Ian A. Wilson, Kevin Wiehe, Laurent Verkoczy, Rogier W. Sanders
Summary: Targeting germline precursors of broadly neutralizing antibodies (bNAbs) is an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs, which require extensive somatic hypermutation, can be optimized for vaccine-induced affinity maturation by selecting boosting immunogens. The results demonstrate proof of concept for generating cross-reactive antibody responses that require rare insertions and deletions.
CELL REPORTS MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Hannah Bauer-Smith, Abigail S. L. Sudol, Stephen A. Beers, Max Crispin
Summary: Antibodies play an important role in immune recruitment or clearance of immune complexes through their interaction with cellular Fc receptors. The presence of endogenous immunoglobulin can affect the engagement of cellular receptors. This review examines the factors controlling serum IgG levels and discusses how endogenous IgG influences the functional activation thresholds of low- and high-affinity Fc receptors. Furthermore, it explores the potential of antibody engineering and pharmacological control to overcome physiological limitations and enhance antibody therapeutics.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Immunology
Osman Dadas, Joel D. Allen, Sarah L. Buchan, Jinny Kim, H. T. Claude Chan, C. Ian Mockridge, Patrick J. Duriez, Anne Rogel, Max Crispin, Aymen Al-Shamkhani
Summary: This study investigates the generation and activity of soluble variants of CD70 and compares their efficacy with an agonist anti-CD27 antibody. The results show that dtCD70-Fc, a dimer-of-trimer protein, can enhance T cell proliferation in vitro, but is less effective than anti-CD27 antibody in boosting a CD8 T cell vaccine response in vivo. However, reducing the glycosylation of dtCD70-Fc improves its half-life and T cell stimulatory activity. Additionally, FcγR binding is found to be important for the maximal boosting of a CD8 T cell response by dtCD70-Fc.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Hannah L. Turner, Abigail M. Jackson, Sara T. Richey, Leigh Antanasijevic, Aleksandar Antanasijevic, Lars Hangartner, Andrew B. Ward
Summary: Electron microscopy-based polyclonal epitope mapping (EMPEM) is a method that can determine the epitope specificities of serum antibodies to a given antigen after vaccination or infection. This article presents a protocol for the rapid high throughput assessment of antibody responses to glycoprotein antigens in vaccination and infection studies using the EMPEM method. The protocol includes steps for antibody isolation and digestion, antigen complex and purification, as well as electron microscope imaging, and detailed procedures for processing and analysis of EMPEM data.
Article
Biochemical Research Methods
Alba Torrents de la Pena, Leigh M. Sewall, Rebeca de Paiva Froes Rocha, Abigail M. Jackson, Payal P. Pratap, Sandhya Bangaru, Christopher A. Cottrell, Subhasis Mohanty, Albert C. Shaw, Andrew B. Ward
Summary: Understanding antibody-antigen interactions in polyclonal immune responses is crucial for vaccine design. Photo-cross-linking and electron microscopy were used to detect low-affinity and low-abundance antibodies, providing a broader structural characterization of immune responses. This technique can be used to study antibody binding mechanisms and design vaccine immunogens in early time points.
CELL REPORTS METHODS
(2023)