Scientific Publications by FDA Staff

Cell Host Microbe 2020 Feb 12;27(2):262-76

Longitudinal human antibody repertoire against complete Ebola virus proteome following natural infection reveals immune markers of protection.

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

The longitudinal antibody repertoire against the entire Ebola virus (EBOV) proteome was characterized in an acutely infected patient receiving supportive care alone in order to identify potential immune markers of protection. Differential kinetics of IgM/IgG/IgA epitope diversity, antibody binding, and affinity maturation to EBOV proteins were observed. During acute illness, antibody binding to VP40 and GP predominated, followed by binding to VP30, VP35, VP24 and NP. At day 13 of clinical illness, antibody binding to most EBOV proteins and affinity maturation to GP displayed an inflection point after which illness severity declined rapidly. At one-year post illness onset, IgG immunodominance to VP40 and GP and a diverse IgM repertoire were observed despite undetectable virus. Novel antigenic sites at the C-terminus of GP1 and in highly conserved GP2-HR2 protected vaccinated mice against lethal EBOV challenge. These findings may aid the development, evaluation, and implementation of effective countermeasures against Ebola virus disease.