A Study of Molecular Mimicry and Immunological Cross‐reactivity between Hepatitis B Surface Antigen and Myelin Mimics

Abstract

On the basis of the reported association between hepatitis B vaccination (HBvacc) and autoimmune demyelinating complications such as multiple sclerosis (MS), we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg), and the MS‐autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of immunological cross‐reactivity. Twenty‐mer peptides spanning 4 SHBsAg/MOG and 1 SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as targets of cross‐reactive responses. A total of 147 samples from 58 adults were collected before HBvacc (58/58), and post‐HBvacc (48/58 before the second and 41/58 before the third boost). Eighty‐seven sera from anti‐SHBsAg antibody negative patients with various diseases were tested as pathological controls. Reactivity to at least one of the SHBsAg peptides was found in 8 (14%) pre‐HBvacc subjects; amongst the remaining 50, reactivity to at least one of the SHBsAg peptides appeared in 47 (94%) post‐HBvacc. Reactivity to at least one of the MOG mimics was present in 4 (8%) pre‐HBvacc and in 30 (60%) post‐HBvacc (p < 0.001). Overall 30/50 (60%) vaccinees had SHBsAg/MOG double reactivity on at least one occasion compared to none before‐vaccination and in 2 (2%) of the pathological controls (p < 0.001 for both). SHBsAg/MOG double reactivity was cross‐reactive as confirmed by inhibition studies. At 6 months post‐vaccination, 3 of the 4 anti‐MOG reactive cases before vaccination and 7 of the 24 (29%) of the anti‐MOG reactive cases at 3 months post‐vaccination had lost their reactivity to MOG5-24. There was no reactivity to the SHBsAg/MBP mimics. None of the vaccinees reported symptoms of demyelinating disorders. In view of the observed SHBsAg/MOG cross‐reactivity, the vaccine′s possible role as an immunomodulator of viral/self cross‐reactivity must be further investigated.