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Cell Host Microbe. 2020 Feb 12;27(2):262-276.e4. doi: 10.1016/j.chom.2020.01.001.

Longitudinal Human Antibody Repertoire against Complete Viral Proteome from Ebola Virus Survivor Reveals Protective Sites for Vaccine Design.

Author information

1
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA. Electronic address: surender.khurana@fda.hhs.gov.
2
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA.
3
United States Army, Medical Research Institute of Infectious Diseases, Viral Immunology Branch, Virology Division, Fort Detrick, Frederick, MD 21702, USA.
4
Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA.
5
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
6
Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Evolution of antibody repertoire against the Ebola virus (EBOV) proteome was characterized in an acutely infected patient receiving supportive care alone to elucidate virus-host interactions over time. Differential kinetics are observed for IgM-IgG-IgA epitope diversity, antibody binding, and affinity maturation to EBOV proteins. During acute illness, antibodies predominate to VP40 and glycoprotein (GP). At day 13 of clinical illness, a marked increase in antibody titers to most EBOV proteins and affinity maturation to GP is associated with rapid decline in viral replication and illness severity. At one year, despite undetectable virus, a diverse IgM repertoire against VP40 and GP epitopes is observed suggesting occult viral persistence. Rabbit immunization experiments identify key immunodominant sites of GP, while challenge studies in mice found these epitopes induce EBOV-neutralizing antibodies and protect against lethal EBOV challenge. This study reveals markers of viral persistence and provides promising approaches for development and evaluation of vaccines and therapeutics.

KEYWORDS:

Ebola; GFPDL; GP; affinity; antibody; correlates of protection; epitope mapping; genome-fragment phage display library; glycoprotein; immune response; infection; neutralization; vaccine; virus

PMID:
32053790
DOI:
10.1016/j.chom.2020.01.001

Conflict of interest statement

Declaration of Interests The authors declare no competing interests. The GFPDL technology and Ebola peptide sequences described in this study are covered under US patent application.

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