Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees.

Jose Mateus,Simon Mallal,Michael A. Angelo,Alessandro Sette,Elizabeth Phillips,Daniela Weiskopf,Alba Grifoni,Hannah Voic,John Sidney

doi:10.3390/v12111300

Abstract

Yellow fever virus (YFV) is a mosquito-borne member of the genus flavivirus, including other important human-pathogenic viruses, such as dengue, Japanese encephalitis, and Zika. Herein, we report identifying 129 YFV Class II epitopes in donors vaccinated with the live attenuated YFV vaccine (YFV-17D). A total of 1156 peptides predicted to bind 17 different common HLA-DRB1 allelic variants were tested using IFNγ ELISPOT assays in vitro re-stimulated peripheral blood mononuclear cells from twenty-six vaccinees. Overall, we detected responses against 215 YFV epitopes. We found that the capsid and envelope proteins, as well as the non-structural (NS) proteins NS3 and NS5, were the most targeted proteins by CD4+ T cells from YF-VAX vaccinated donors. In addition, we designed and validated by flow cytometry a CD4+ mega pool (MP) composed of structural and non-structural epitopes in an independent cohort of vaccinated donors. Overall, this study provides a comprehensive prediction and validation of YFV epitopes in a cohort of YF-17D vaccinated individuals. With the design of a CD4 epitope MP, we further provide a useful tool to detect ex vivo responses of YFV-specific CD4 T cells in small sample volumes.

Highlights

Yellow fever (YF) is a mosquito-borne acute viral disease, currently endemic to the tropical and subtropical regions of Africa and the Americas
Our goal was to identify a comprehensive set of Yellow Fever epitopes by assessing the CD4+
To ensure that our donor cohort was representative of the general population, we compared frequencies of the main HLA class II alleles observed in our donor cohort with those observed in our repository of over 3500 donors, reflecting a variety of clinical studies and a diverse set of ethnicities, ranging from the USA, South and Central

Summary

Introduction

Yellow fever (YF) is a mosquito-borne acute viral disease, currently endemic to the tropical and subtropical regions of Africa and the Americas. YF is caused by the yellow fever virus (YFV), an RNA virus from the flavivirus genus, which is closely related to the dengue, Japanese encephalitis, Zika, and tick-borne encephalitis viruses [2]. Before introducing large-scale vaccination, the impact of YF epidemics on human health, especially amongst children and the elderly, was staggering [3]. Development of the live attenuated YF-17D based vaccines (17D-204 and 17DD) in the late 1930s and subsequent large-scale immunization programs, led to the control and virtual elimination of urban epidemics. The yellow fever 17D-based vaccine (YF-17D) is a live attenuated vaccine produced by Sanofi Pasteur under the tradename YF-VAX®and is the only YF vaccine licensed in the United States [4]

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