Early IFN-gamma production after YF 17D vaccine virus immunization in mice and its association with adaptive immune responses.

Patrícia C C Neves,Ricardo Galler,Juliana R Santos,Luciana N Tubarão,Myrna C Bonaldo,Paulo Lee Ho

doi:10.1371/journal.pone.0081953

Abstract

Yellow Fever vaccine is one of the most efficacious human vaccines ever made. The vaccine (YF 17D) virus induces polyvalent immune responses, with a mixed TH1/TH2 CD4+ cell profile, which results in robust T CD8+ responses and high titers of neutralizing antibody. In recent years, it has been suggested that early events after yellow fever vaccination are crucial to the development of adequate acquired immunity. We have previously shown that primary immunization of humans and monkeys with YF 17D virus vaccine resulted in the early synthesis of IFN-γ. Herein we have demonstrated, for the first time that early IFN-γ production after yellow fever vaccination is a feature also of murine infection and is much more pronounced in the C57BL/6 strain compared to the BALB/c strain. Likewise, in C57BL/6 strain, we have observed the highest CD8+ T cells responses as well as higher titers of neutralizing antibodies and total anti-YF IgG. Regardless of this intense IFN-γ response in mice, it was not possible to see higher titers of IgG2a in relation to IgG1 in both mice lineages. However, IgG2a titers were positively correlated to neutralizing antibodies levels, pointing to an important role of IFN-γ in eliciting high quality responses against YF 17D, therefore influencing the immunogenicity of this vaccine.

Highlights

Yellow Fever vaccine was developed during 30 ́s by Max Theiler and cols and has been in current use for human vaccination since it
This early IFN- γ production was attributed to γδ T cells and was shown to be a feature of yellow fever vaccination [8]
Corroborating this previous study, we have demonstrated that early IFN-γ production after yellow fever vaccination is a characteristic of murine infection and is much more pronounced in the C57BL/6 strain when compared to the BALB/c strain

Summary

Introduction

Yellow Fever vaccine was developed during 30 ́s by Max Theiler and cols and has been in current use for human vaccination since it It confers long term protection after only a single dose and more than 540 million doses have been administered globally [1]. Vaccination with YF 17D virus induces polyvalent immune responses, with a mixed TH1/TH2 CD4+ cell profile, which results in robust T CD8+ responses and high titers of neutralizing antibody [2]. Despite these characteristics, until few years ago, very little was known about the cellular and molecular mechanisms that lead to such good immune response. It is becoming clear that early events following YF 17D immunization have a key role in determining the strength and quality of the adaptive immune response [3,4,5,6,7].

Methods

Results

Conclusion