Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

Wei Zhao,Karol Sestak,Bapi Pahar

doi:10.4137/vrt.s563

Abstract

A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6) CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8]) of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA) in plasma. To measure the interferon gamma (IFN-γ) and tumor necrosis factor (TNF) anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6(161-395) region revealed reactivity of CD4+ T cells with the VP6(281-331) domain. A VP6(301-315) region was identified as the epitope responsible for IFN-γ production while a broader VP6(293-327) domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

Highlights

A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6) CD4+ T cell epitopes
Humoral immunity has been identified as an important component of protection against rotavirus infection in various animal models (Conner et al 1991; O'Neal et al 1997; Ruggeri et al 1998; Yuan et al 1998; Yuan and Saif, 2002; Jiang et al 2002; Gonzalez et al 2003), several studies have suggested that T cell-mediated immunity plays a role (Banos et al 1997; Jaimes et al 2002, 2004, 2005; Rojas et al 2003; McNeal et al 2002, 2007)
Our studies with rotavirus-infected rhesus macaques corroborated that production of IFN-γ and other inflammatory cytokines by CD4+ and CD8+ T cells does occur in rotavirusinfected primates (Sestak et al 2004)

Summary

Introduction

A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6) CD4+ T cell epitopes. Our studies with rotavirus-infected rhesus macaques corroborated that production of IFN-γ and other inflammatory cytokines by CD4+ and CD8+ T cells does occur in rotavirusinfected primates (Sestak et al 2004).

Results

Conclusion