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Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque
Wei Zhao1, Bapi Pahar, Karol Sestak
1Tulane National Primate Research Center, Covington, LA, U.S.A.
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.
Insights
Rhesus macaques infected with human rotavirus identified specific viral protein 6 (VP6) epitopes. This non-human primate model aids in discovering T cell targets crucial for developing pediatric rotavirus vaccines.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Rotavirus remains a leading cause of severe diarrheal disease in infants globally.
- Identifying specific viral protein 6 (VP6) T cell epitopes is crucial for developing effective rotavirus vaccines.
- Non-human primate models offer a valuable platform for studying human infectious diseases and vaccine responses.
Purpose of the Study:
- To evaluate a non-human primate model for identifying rotavirus VP6 CD4+ T cell epitopes.
- To characterize the T cell response to VP6 epitopes in rotavirus-infected rhesus macaques.
- To identify specific VP6 domains responsible for interferon gamma (IFN-γ) and tumor necrosis factor (TNF) production.
Main Methods:
- Four juvenile rhesus macaques were inoculated with a mixed human rotavirus inoculum (G1P[8] and G9P[8]).
- Peripheral blood cells from an infected macaque were stimulated in vitro with VP6 peptides.
- Interferon gamma (IFN-γ) and tumor necrosis factor (TNF) production by CD4+ T cells were measured.
Main Results:
- Infection and rotavirus G1P[8] shedding were achieved in macaques lacking pre-existing rotavirus immunoglobulin A (IgA).
- CD4+ T cell reactivity was observed with the VP6(281-331) domain from simian rotavirus VP6(161-395) region.
- A specific epitope VP6(301-315) induced IFN-γ production, while a broader domain VP6(293-327) induced TNF production.
Conclusions:
- Rotavirus-infected macaques can serve as a model for identifying CD4+ T cell epitopes.
- This model facilitates the discovery of T cell epitopes relevant to pediatric rotavirus vaccine development.
- Further studies using this model can address specific immunological questions for vaccine design.
