n-Dodecyl-β-D-maltoside inhibits aggregation of human interferon-β-1b and reduces its immunogenicity.
The development of neutralizing antibodies to the protein drug interferon-β is a significant impediment to its use in the treatment of multiple sclerosis. Neutralizing antibodies to interferon-β arise from aggregation of the peptide during manufacturing and storage. We tested the ability of dodecylmaltoside, a nontoxic alkylsaccharide surfactant, to reduce aggregation of interferon-β in vitro and to reduce its immunogenicity in vivo. Interferon-β, in solution with and without dodecylmaltoside, was periodically evaluated for aggregation by light scatter for 1 month. Interferon-β, with and without dodecylmaltoside, was given 3 days/week for 1 month to mice; the sera of these mice were analyzed for anti-interferon-β antibodies by ELISA. Dodecylmaltoside reduces the aggregation of interferon-β in vitro and its immunogenicity in vivo. Our positive findings warrant additional tests of dodecylmaltoside as a therapeutic adjuvant in rodent models of multiple sclerosis.
Rifkin
Robert A
RA
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-0005, USA. rrifkin2@jhmi.edu
Maggio
Edward T
ET
Dike
Sonny
S
Kerr
Douglas A
DA
Levy
Michael
M
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000917:Antibody Formation / Q000187:drug effects*; D003902:Detergents / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000494:pharmacology*; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D019798:Neopterin / Q000097:blood
D057134:Antibodies, Neutralizing; D003902:Detergents; D005079:Excipients; D005960:Glucosides; D000068576:Interferon beta-1b; D019798:Neopterin; C040358:dodecyl maltoside; D016899:Interferon-beta