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

التفاصيل البيبلوغرافية
العنوان: A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus
المؤلفون: Robert F. Garry, Sharon L. Schendel, Mambu Momoh, Bronwyn M. Gunn, Yoshihiro Kawaoka, Galit Alter, Augustine Goba, Jiyoung Kim, Richard Lu, John S. Schieffelin, Lansana Kanneh, Erica Ollmann Saphire, Kai Huang, Matthew D. Slein, Kristian G. Andersen, Don Grant, Matthias Pauthner, Todd J. Suscovich, Vicky Roy, Caitlin Cain, Ayato Takada, Peter Halfmann, Philipp A. Ilinykh, Alexander Bukreyev, Caroline Atyeo
المصدر: Immunity
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, medicine.drug_class, Immunology, Disease, Receptors, Fc, medicine.disease_cause, Monoclonal antibody, Antibodies, Viral, Article, 03 medical and health sciences, Immunoglobulin Fab Fragments, 0302 clinical medicine, In vivo, Immunity, medicine, Immunology and Allergy, Animals, Humans, Neutralizing antibody, Antibody-dependent cell-mediated cytotoxicity, Mice, Inbred BALB C, Innate immune system, Ebola virus, biology, Effector, Antibody-Dependent Cell Cytotoxicity, Hemorrhagic Fever, Ebola, Ebolavirus, Antibodies, Neutralizing, Immunoglobulin Fc Fragments, 030104 developmental biology, Infectious Diseases, HEK293 Cells, 030220 oncology & carcinogenesis, Immunoglobulin G, Humoral immunity, Antibody Formation, biology.protein, Female, Antibody
الوصف: Summary 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.
تدمد: 1097-4180
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cffb9e61603cdebe2a2675c625184e34
https://pubmed.ncbi.nlm.nih.gov/33852832
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....cffb9e61603cdebe2a2675c625184e34
قاعدة البيانات: OpenAIRE
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