An Absence of Epstein-Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination.

Peter A C Maple,David I Pritchard,Bruno Gran,Cris S Constantinescu,Radu Tanasescu

doi:10.3390/vaccines8030487

Abstract

Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG.

Highlights

The hookworms Necator americanus and Ancylostoma duodenale are nematode roundworms which belong to a larger group of helminth multicellular worms that include cestode tapeworms and trematode flukes
In this study, which commenced during 2012, 35 people with multiple sclerosis (PwMS) were treated with the hookworm N. americanus
The rationale for this study was that natural hookworm infection promoted an anti-inflammatory Th2 and regulatory T cell immune phenotype, which would be beneficial for PwMS who typically show regulatory B and T cell dysfunction [22,23] leading to excessive inflammatory activation and a predominant Th1 immune phenotype

Summary

Introduction

The hookworms Necator americanus and Ancylostoma duodenale are nematode roundworms which belong to a larger group of helminth multicellular worms that include cestode tapeworms and trematode flukes. Animal models and human studies have both provided evidence supporting an immunomodulatory effect of helminth infection on several autoimmune conditions including the relapsing and remitting form of MS [8]. In view of these associations, there has been considerable interest in the application of helminth therapy for the treatment of multiple sclerosis and several small-scale studies have been reported [8,9]. MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1). Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2%

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Discussion

Conclusion