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The Effect of Targeted Vaccination Against Mycobacterium Avium ssp. Paratuberculosis (MAP) in a Multiple Sclerosis Mouse Model: Implications for Causation

Michael R. Warmoth
doi: https://doi.org/10.1101/202275
Michael R. Warmoth
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Abstract

Epidemiologic evidence relating to the causation of Multiple Sclerosis, based upon twin concordance studies, implicates both genetic and environmental contributions. The HLA-DRB1/ HLA-A haplotype confers a 23 fold increase in MS prevalence above its baseline of 1 per 1,000 persons. Epigenetic factors, such as an aberrant response to Epstein Barr Virus (EBV) and Vitamin D deficiency can increase that risk 36 and 2 fold respectively. Evidence of an association between elevated MAP antibodies and Multiple Sclerosis has been reported.

A prospective randomized controlled trial was performed in SJL mice exposed to the myelin-related oligopeptide PLP139-151; a relapsing-remitting Experimental Autoimmune Encephalitis (EAE) model. 100 mice were randomized into five groups of 20. Group 1-Unimmunized prior to disease induction. Group 2-Immunized twice with a 74 kDa fusion protein vaccine against MAP; delivered 28 days and 7 days prior to disease induction. Group 3- 1 dose of 74 kDa vaccine 10 days post-disease induction. Group 4- Attenuated whole cell MAP vaccine (ΔSigH) 28 days prior to disease induction. Group 5- ΔSigH vaccine 10 days post disease induction.

Disability was quantified using a EAE disability scoring reference ranging from 0 to 5.

Significant decreases in peak disability were seen in the bimodal peaks of this relapsing-remitting model 38% (p<0.006) and 40% (p<0.001). ΔsigH immunized mice lost half as much weight as controls post disease induction. The results suggest that environmental MAP antigen exposure may play an etiologic role in the development of EAE.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 12, 2017.
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The Effect of Targeted Vaccination Against Mycobacterium Avium ssp. Paratuberculosis (MAP) in a Multiple Sclerosis Mouse Model: Implications for Causation
Michael R. Warmoth
bioRxiv 202275; doi: https://doi.org/10.1101/202275
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The Effect of Targeted Vaccination Against Mycobacterium Avium ssp. Paratuberculosis (MAP) in a Multiple Sclerosis Mouse Model: Implications for Causation
Michael R. Warmoth
bioRxiv 202275; doi: https://doi.org/10.1101/202275

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