pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity

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.

Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

“…Mononuclear cells infiltrated in the CNS were obtained as previously described ( 38 ). Nineteen days after EAE induction, mice were anesthetized with ketamine/xylazine and perfused with 10 mL saline solution.…”

Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective

“…The clinical features were accompanied by a lower frequency of pro-inflammatory T-cells (IFN-γ-producing and Th17), an increase in anti-inflammatory IL-10-secreting T-cells, lower T-cell infiltration, and a greater microglia shift towards an M2 subtype [127]. Experimental vaccination studies also attempt at upregulating the anti-inflammatory Treg cell populations [130]. A vaccine containing pVAX vector, which contained a Mycobacterium leprae-derived gene that encoded heat-shock protein 65 (hsp65), was produced [130].…”

“…Experimental vaccination studies also attempt at upregulating the anti-inflammatory Treg cell populations [130]. A vaccine containing pVAX vector, which contained a Mycobacterium leprae-derived gene that encoded heat-shock protein 65 (hsp65), was produced [130]. After four doses of the pVAXhsp65 vaccine, the vaccinated EAE mice demonstrated higher levels of IFN-γ and anti-inflammatory IL-10 cytokines [130].…”

“…A vaccine containing pVAX vector, which contained a Mycobacterium leprae-derived gene that encoded heat-shock protein 65 (hsp65), was produced [130]. After four doses of the pVAXhsp65 vaccine, the vaccinated EAE mice demonstrated higher levels of IFN-γ and anti-inflammatory IL-10 cytokines [130]. Despite the cytokine alterations and some clinical improvement, no peripheral nor CNS changes in the frequency of autoimmune CD4 + /CD25 + /Foxp3 + T-cells were noted [130].…”

Peptide-Based Vaccination Therapy for Rheumatic Diseases

“…Studies in recent years have suggested that peptidebased vaccinations are promising in treating diseases such as cancer and allergic diseases, and some have shown impressive clinical benefits [22][23][24]. Besides, peptide-based vaccination has also been proposed as a promising immunotherapy for autoimmune diseases such as type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) [25][26][27]. Some studies also have reported encouraging findings on peptide-based immunotherapeutic vaccinations in rheumatic diseases [28][29][30][31][32].…”