PVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity.

Sofia Fernanda Gonçalves Zorzella-Pezavento,Maura Rosane Valerio Ikoma,Fernanda Chiuso-Minicucci,Alexandrina Sartori,Célio Lopes Silva,Priscila Maria Colavite,Thais Graziela Donegá França,Larissa Camargo Da Rosa,Bianca Balbino,Camila Marques,Ana Paula Masson,Larissa Lumi Watanabe Ishikawa

doi:10.1155/2017/6257958

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) emulsified in Complete Freund's Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35–55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction.

Highlights

Multiple sclerosis (MS) is a progressive inflammatory disease that damages the brain and the spinal cord
Experimental autoimmune encephalomyelitis (EAE) is an induced demyelinating pathology of the central nervous system (CNS) that is commonly used as a model to investigate this disease
To evaluate the prophylactic effect of pVAXhsp65 on EAE development, mice were immunized with 4 pVAXhsp65 doses and 14 days after last dose they were submitted to EAE induction

Summary

Introduction

Multiple sclerosis (MS) is a progressive inflammatory disease that damages the brain and the spinal cord. A plethora of reports support the view that it is mediated by autoreactive T cells specific for myelin antigens [1, 2] Once they had been activated in the periphery, these self-specific T cells cross the blood-brain barrier and destroy the myelin sheets and axons from central neurons [3,4,5]. This demyelination is responsible for signal conduction slowing or even signal blockage [6].

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