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

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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Khurana S,Ravichandran S,Hahn M,Coyle EM,Stonier SW,Zak SE,Kindrachuk J,Davey RT Jr,Dye JM,Chertow DS

doi

10.1016/j.chom.2020.01.001

subject

Has Abstract

pub_date

2020-02-12 00:00:00

pages

262-276.e4

issue

2

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(20)30001-9

journal_volume

27

pub_type

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