Functional Neutralizing Monoclonal Antibodies F-2-1 Against gp42 Ameliorates Disease Progression in Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), occurring in isolated attacks or progressive forms. Many observations implicate Epstein-Barr virus (EBV) in the pathogenesis of MS. With the relentless accumulation of evidence for a significant pathogenic role of EBV in MS, I believe it may be possible to prevent and cure MS by effectively controlling EBV infection. Currently, monoclonal antibodies (MAb) are used as therapeutics for a molecular targeted approach to slowing disease progression in MS. However, to my knowledge, there have been no antibodies targeted against EBV infection in any model of MS. The objective of this study is to determine whether or not a MAb against EBV could be a therapeutic target for EAE. In this study, I will propose an experiment that will examine the effects of intraperitoneal injection of MAb F-2-1 in 2-month-old new humanized BALB/c Rag2-/- ll2rg-/- (BRG) adult EBV/EAE male mice. My expected results suggest that mice with EBV/EAE + MAb F-2-1 may have an attenuated clinical disease course. Through immunohistochemical studies, I will also propose that MAb F-2-1 may decrease inflammation, demyelination and axonal loss in the CNS of mice with EAE. I believe that this novel treatments success would depend on MAb F-2-1’s ability to inhibit clonal expansion of EBV-infected autoreactive B cell in the CNS. Ultimately, my proposed experiment suggests that inhibition of virus-cell fusion of EBV to the B cell membrane might attenuate neuropathology in EAE. I hope that my prospective study highlights the importance of controlling EBV in patients with MS and provides grounds for optimism on how to successfully treat MS by controlling EBV infection. In conclusion, by proposing an alternative therapeutic approach, I hope that this hypothetical experiment will aid in future investigations that could further our knowledge on treatment and prevention of multiple sclerosi