Characterization of yellow fever virus (YFV)-specific antibodies in individuals infected with YFV or vaccinated with 17DD

Abstract

Yellow fever is still considered a public health problem in several regions of the world, including Brazil, where a major outbreak has recently occurred at southeastern region, with more than 290 confirmed cases and 97 deaths. The yellow fever vaccine, developed over eight decades ago, is highly effective at conferring protective immunity against yellow fever virus (YFV) for a period of 10 years or more. In particular, the production of neutralizing antibodies (Abs) is one of the main pillars of individual protection induced by the vaccine. Although the efficacy of the vaccine is well established, the coverage of vaccination is poor and there is no specific treatment for yellow fever, which has a relatively high mortality rate. Facing the constant challenges for the control of YFV and considering the relevance of neutralizing Abs in the prevention of viral replication, the therapeutic use of these molecules may represent a promising strategy, especially in the areas of relatively low vaccination coverage. Thus, the objective of this project is to characterize the kinetics of Abs producing cells, plasmablasts, as well as the repertoire of monoclonal Abs (mAbs) derived from individuals that are infected with YFV or vaccinated with the 17DD formulation. In fact, the characterization of the Abs repertoire is considered a crucial step for the development of preventive and therapeutic strategies based on the use of mAbs.In this study, circulating plasmablast cells will be identified by multiparametric flow cytometry during acute YFV-infection as well as before and after vaccination. Single CD27high CD38high B cells derived from peripheral blood of the volunteers with plasmablasts expansion will be individually isolated in 96-wells plates and the respective variable Ig heavy (VH) and light (VL) chain sequences will be amplified and sequenced for further analysis. This study will provide more consistent data on the humoral response to YFV and improve knowledge about the neutralizing Abs of this infection. (AU)