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  • Perspective
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EBOLA VIRUS

Antibody-mediated protection against Ebola virus

Nature Immunology volume 19, pages 1169–1178 (2018)Cite this article

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Abstract

Recent Ebola virus disease epidemics have highlighted the need for effective vaccines and therapeutics to prevent future outbreaks. Antibodies are clearly critical for control of this deadly disease; however, the specific mechanisms of action of protective antibodies have yet to be defined. In this Perspective we discuss the antibody features that correlate with in vivo protection during infection with Ebola virus, based on the results of a systematic and comprehensive study of antibodies directed against this virus. Although neutralization activity mediated by the Fab domains of the antibody is strongly correlated with protection, recruitment of immune effector functions by the Fc domain has also emerged as a complementary, and sometimes alternative, route to protection. For a subset of antibodies, Fc-mediated clearance and killing of infected cells seems to be the main driver of protection after exposure and mirrors observations in vaccination studies. Continued analysis of antibodies that achieve protection partially or wholly through Fc-mediated functions, the precise functions required, the intersection with specificity and the importance of these functions in different animal models is needed to identify and begin to capitalize on Fc-mediated protection in vaccines and therapeutics alike.

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Fig. 1: Evaluation of early antibody treatments for their protection of NHPs.
Fig. 2: Antibody treatments approved for evaluation in outbreaks of Ebola virus in 2018.
Fig. 3: Structure, epitopes of Ebola virus GP, and antibody functions.
Fig. 4: Outliers in the VIC study.
Fig. 5: Specific glycan profiles are linked to distinct functional activity.

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Acknowledgements

We acknowledge U19AI107962 (a Center of Excellence in Translational Research (CETR) award from NIAID of the US National Institutes of Health), and the members of the Viral Hemorrhagic Fever Immunotherapeutic Consortium who contributed antibodies (many of which were unpublished) and analytical efforts on the project, including K.G. Andersen, A.B. Ward and D.R. Burton; R. Ahmed and C.W. Davis (Emory University); M.J. Aman (Integrated BioTherapeutics); A. Bukreyev (University of Texas Medical Branch); K. Chandran and J.R. Lai (Albert Einstein College of Medicine); J.E. Crowe, Jr. (Vanderbilt University School of Medicine); J.M. Dye (USAMRIID); B. Doranz (Integral Molecular); H. Feldmann (NIAID Rocky Mountain Lab); G. Georgiou (University of Texas); G.G. Olinger and L. Hensley (NIAID Integrated Research Facility); Y. Kawaoka (University of Wisconsin); G.P. Kobinger (Université Laval); K. Wagh and B. Korber (Los Alamos National Labs); F. Krammer (Icahn School of Medicine at Mt. Sinai); C.A. Kyratsous (Regeneron); C. Nykiforuk (Emergent Biosciences); X. Qiu (Public Health Agency of Canada); A. Sprecher (Médecins Sans Frontières); A.R. Townsend (University of Oxford); V. Volchkov (Université Lyon); L.M. Walker (Adimab); C.-I. Wang (A*STAR); L. Zeitlin (Mapp Biopharmaceutical); and the students, postdoctoral fellows, technicians and staff scientists in their labs, as well as J.V. Ravetch (Rockefeller University) for discussions. This is manuscript #29662 from Scripps Research.

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Authors and Affiliations

  1. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA

    Erica Ollmann Saphire, Sharon L. Schendel & Jacob C. Milligan

  2. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA

    Erica Ollmann Saphire

  3. The Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA

    Bronwyn M. Gunn & Galit Alter

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  1. Erica Ollmann Saphire
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  2. Sharon L. Schendel
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  3. Bronwyn M. Gunn
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  4. Jacob C. Milligan
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  5. Galit Alter
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Contributions

E.O.S., S.L.S., B.M.G. and J.C.M. prepared the figures; E.O.S., S.L.S., B.M.G. and G.A. analyzed data and drafted and edited the manuscript; B.M.G. performed the glycan clustering analysis; and E.O.S. and G.A. secured funding.

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Correspondence to Erica Ollmann Saphire or Galit Alter.

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Saphire, E.O., Schendel, S.L., Gunn, B.M. et al. Antibody-mediated protection against Ebola virus. Nat Immunol 19, 1169–1178 (2018). https://doi.org/10.1038/s41590-018-0233-9

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