Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors.

Ariel Sobarzo,Moses Egesa,Andrew Herbert,Shlomit Fedida-Metula,Leslie Lobel,John Dye,Victoria Yavelsky,David Ochayon,Neta Tali,Ana Kuehne,Eli Lewis,Stephen Cose,Julius Lutwama,Yael Eskira,Spencer Stonier

doi:10.3390/v8050133

Abstract

Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000–2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.

Highlights

Ebolavirus is a member of the Filoviridae family and the cause of viral hemorrhagic fever disease [1].Studies that examined the pathogenesis of Ebolavirus infection in humans indicate that recovery is largely dependent upon, and associated with, the development of both cell-mediated and humoralViruses 2016, 8, 133; doi:10.3390/v8050133 www.mdpi.com/journal/virusesViruses 2016, 8, 133 immune responses [2,3,4,5]
Whole blood samples were obtained from 15 survivors of the Sudan virus (SUDV) outbreak in Gulu and five from uninfected members of the Gulu community, which served as controls
The results of our study indicate that long-lasting Sudan virus-specific CD4 T helper cells persist years after recovery in some survivors and, importantly, this phenotype may correlate with serum neutralizing activity

Summary

Introduction

Ebolavirus is a member of the Filoviridae family and the cause of viral hemorrhagic fever disease [1].Studies that examined the pathogenesis of Ebolavirus infection in humans indicate that recovery is largely dependent upon, and associated with, the development of both cell-mediated and humoralViruses 2016, 8, 133; doi:10.3390/v8050133 www.mdpi.com/journal/virusesViruses 2016, 8, 133 immune responses [2,3,4,5]. Studies that examined the pathogenesis of Ebolavirus infection in humans indicate that recovery is largely dependent upon, and associated with, the development of both cell-mediated and humoral. Evidence from studies that examined survivors and asymptomatic cases demonstrated the presence of significant levels of virus-specific. The causative agent of this outbreak was named the Sudan virus (SUDV). Studies of the survivors of this outbreak indicate that the composition of survivor memory immune responses includes pro-inflammatory cytokine responses and antibody responses to SUDV antigens [14,15]. Previous experiments that characterized SUDV survivor immune responses did not measure antiviral memory T cell responses and could not determine the provenance of the cytokines being measured [15].

Results

Discussion

Conclusion