Literature DB >> 33852832

A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.

Bronwyn M Gunn1, Richard Lu1, Matthew D Slein1, Philipp A Ilinykh2, Kai Huang2, Caroline Atyeo1, Sharon L Schendel3, Jiyoung Kim1, Caitlin Cain1, Vicky Roy1, Todd J Suscovich1, Ayato Takada4, Peter J Halfmann5, Yoshihiro Kawaoka5, Matthias G Pauthner6, Mambu Momoh7, Augustine Goba7, Lansana Kanneh7, Kristian G Andersen8, John S Schieffelin9, Donald Grant10, Robert F Garry11, Erica Ollmann Saphire12, Alexander Bukreyev13, Galit Alter14.   

Abstract

Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies. Survivors developed a range of functional antibody responses, and we therefore applied a rapid, high-throughput Fc engineering platform to define the most protective profiles. We generated a library of Fc variants with identical antigen-binding fragments (Fabs) from an EBOV neutralizing antibody. Fc variants with antibody-mediated complement deposition and moderate natural killer (NK) cell activity demonstrated complete protective activity in a stringent in vivo mouse model. Our findings highlight the importance of specific effector functions in antibody-mediated protection, and the experimental platform presents a generalizable resource for identifying correlates of immunity to guide therapeutic antibody design.
Copyright © 2021 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  ADCC; Ebola virus; Fc effector function; antibody engineering; complement; humoral immunity; infectious diseases; monoclonal antibody therapeutics; phagocytosis

Mesh：

Substances：

Year:  2021        PMID： 33852832      PMCID： PMC8111768          DOI： 10.1016/j.immuni.2021.03.009

Source DB:  PubMed          Journal:  Immunity        ISSN： 1074-7613            Impact factor:   31.745


  68 in total

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Review 2.  Properties of mouse and human IgG receptors and their contribution to disease models.

Authors:  Pierre Bruhns
Journal:  Blood       Date:  2012-04-25       Impact factor: 22.113

3.  Differential requirements for FcγR engagement by protective antibodies against Ebola virus.

Authors:  Stylianos Bournazos; David J DiLillo; Arthur J Goff; Pamela J Glass; Jeffrey V Ravetch
Journal:  Proc Natl Acad Sci U S A       Date:  2019-09-04       Impact factor: 11.205

4.  Affinity of human IgG subclasses to mouse Fc gamma receptors.

Authors:  Gillian Dekkers; Arthur E H Bentlage; Tamara C Stegmann; Heather L Howie; Suzanne Lissenberg-Thunnissen; James Zimring; Theo Rispens; Gestur Vidarsson
Journal:  MAbs       Date:  2017-05-02       Impact factor: 5.857

5.  A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever.

Authors:  M Bray; K Davis; T Geisbert; C Schmaljohn; J Huggins
Journal:  J Infect Dis       Date:  1998-09       Impact factor: 5.226

6.  Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors.

Authors:  Jeffrey B Stavenhagen; Sergey Gorlatov; Nadine Tuaillon; Christopher T Rankin; Hua Li; Stephen Burke; Ling Huang; Sujata Vijh; Syd Johnson; Ezio Bonvini; Scott Koenig
Journal:  Cancer Res       Date:  2007-09-15       Impact factor: 12.701

7.  Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV.

Authors:  Jishnu Das; Srivamshi Pittala; Margaret E Ackerman; Thomas Broge; Caitlyn Linde; Todd J Suscovich; Eric P Brown; Todd Bradley; Harini Natarajan; Shu Lin; Jessica K Sassic; Sean O'Keefe; Nickita Mehta; Derrick Goodman; Magdalena Sips; Joshua A Weiner; Georgia D Tomaras; Barton F Haynes; Douglas A Lauffenburger; Chris Bailey-Kellogg; Mario Roederer; Galit Alter
Journal:  Nat Med       Date:  2018-09-03       Impact factor: 53.440

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Journal:  Immunity       Date:  2018-07-17       Impact factor: 31.745

9.  A role for immune complexes in enhanced respiratory syncytial virus disease.

Authors:  Fernando P Polack; Michael N Teng; Peter L Collins; Gregory A Prince; Marcus Exner; Heinz Regele; Dario D Lirman; Richard Rabold; Scott J Hoffman; Christopher L Karp; Steven R Kleeberger; Marsha Wills-Karp; Ruth A Karron
Journal:  J Exp Med       Date:  2002-09-16       Impact factor: 14.307

10.  Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

Authors:  Xiangguo Qiu; Gary Wong; Jonathan Audet; Alexander Bello; Lisa Fernando; Judie B Alimonti; Hugues Fausther-Bovendo; Haiyan Wei; Jenna Aviles; Ernie Hiatt; Ashley Johnson; Josh Morton; Kelsi Swope; Ognian Bohorov; Natasha Bohorova; Charles Goodman; Do Kim; Michael H Pauly; Jesus Velasco; James Pettitt; Gene G Olinger; Kevin Whaley; Bianli Xu; James E Strong; Larry Zeitlin; Gary P Kobinger
Journal:  Nature       Date:  2014-08-29       Impact factor: 49.962
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  9 in total

1.  The antibody-binding Fc gamma receptor IIIa / CD16a is N-glycosylated with high occupancy at all five sites.

Authors:  Elizabeth A Lampros; Paul G Kremer; Jesús S Aguilar Díaz de León; Elijah T Roberts; Maria Carolina Rodriguez Benavente; I Jonathan Amster; Adam W Barb
Journal:  Curr Res Immunol       Date:  2022-06-09

Review 2.  Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection.

Authors:  Bronwyn M Gunn; Shuangyi Bai
Journal:  Hum Vaccin Immunother       Date:  2021-10-06       Impact factor: 3.452

3.  Complement-Mediated Neutralisation Identified in Ebola Virus Disease Survivor Plasma: Implications for Protection and Pathogenesis.

Authors:  Jack Mellors; Tom Tipton; Sarah Katharina Fehling; Joseph Akoi Bore; Fara Raymond Koundouno; Yper Hall; Jacob Hudson; Frances Alexander; Stephanie Longet; Stephen Taylor; Andrew Gorringe; N'Faly Magassouba; Mandy Kader Konde; Julian Hiscox; Thomas Strecker; Miles Carroll
Journal:  Front Immunol       Date:  2022-04-12       Impact factor: 8.786

Review 4.  Avidity in antibody effector functions and biotherapeutic drug design.

Authors:  Simone C Oostindie; Greg A Lazar; Janine Schuurman; Paul W H I Parren
Journal:  Nat Rev Drug Discov       Date:  2022-07-05       Impact factor: 112.288

5.  SARS-CoV-2 mRNA vaccination elicits broad and potent Fc effector functions to VOCs in vulnerable populations.

Authors:  Andrew P Hederman; Harini Natarajan; Joshua A Wiener; Peter F Wright; Evan M Bloch; Aaron A R Tobian; Andrew D Redd; Joel N Blankson; Amihai Rottenstreich; Gila Zarbiv; Dana Wolf; Tessa Goetghebuer; Arnaud Marchant; Margaret E Ackerman
Journal:  medRxiv       Date:  2022-09-18

6.  Associations Between Antibody Fc-Mediated Effector Functions and Long-Term Sequelae in Ebola Virus Survivors.

Authors:  Dominic Paquin-Proulx; Bronwyn M Gunn; Aljawharah Alrubayyi; Danielle V Clark; Matthew Creegan; Dohoon Kim; Hannah Kibuuka; Monica Millard; Salim Wakabi; Leigh Anne Eller; Nelson L Michael; Randal J Schoepp; Matthew J Hepburn; Lisa E Hensley; Merlin L Robb; Galit Alter; Michael A Eller
Journal:  Front Immunol       Date:  2021-05-20       Impact factor: 7.561

7.  An intranasal vaccine durably protects against SARS-CoV-2 variants in mice.

Authors:  Ahmed O Hassan; Swathi Shrihari; Matthew J Gorman; Baoling Ying; Dansu Yuan; Saravanan Raju; Rita E Chen; Igor P Dmitriev; Elena Kashentseva; Lucas J Adams; Colin Mann; Meredith E Davis-Gardner; Mehul S Suthar; Pei-Yong Shi; Erica Ollmann Saphire; Daved H Fremont; David T Curiel; Galit Alter; Michael S Diamond
Journal:  Cell Rep       Date:  2021-07-10       Impact factor: 9.995

Review 8.  Development and Structural Analysis of Antibody Therapeutics for Filoviruses.

Authors:  Xiaoying Yu; Erica Ollmann Saphire
Journal:  Pathogens       Date:  2022-03-18

9.  Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma.

Authors:  Pavlo Gilchuk; Adrian Guthals; Stefano R Bonissone; Jared B Shaw; Philipp A Ilinykh; Kai Huang; Robin G Bombardi; Jenny Liang; Ariadna Grinyo; Edgar Davidson; Elaine C Chen; Bronwyn M Gunn; Galit Alter; Erica Ollmann Saphire; Benjamin J Doranz; Alexander Bukreyev; Larry Zeitlin; Natalie Castellana; James E Crowe
Journal:  Front Immunol       Date:  2021-07-16       Impact factor: 7.561
  9 in total

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