Antigenic mimicry-mediated anti-prion effects induced by bacterial enzyme succinylarginine dihydrolase in mice.
Prions, the causative agents of prion diseases, are immunologically tolerated because their major component, prion protein (PrP), is a host-encoded molecule. Therefore, no effective prion vaccines have been developed. We previously showed that heterologous bovine and sheep PrP immunizations of mice overcame tolerance by an antigenic mimicry mechanism to efficiently induce anti-PrP auto-antibodies (Abs), significantly prolonging incubation times in mice subsequently infected with the mouse-adapted Fukuoka-1 prion. These results prompted us to investigate if non-mammal derived molecules able to antigenically mimic anti-prion epitopes, could act as prion vaccines. We show here that immunization of mice with recombinant succinylarginine dihydrolase, a bacterial enzyme with a peptide sequence similar to an anti-prion epitope, induced anti-PrP auto-Abs with anti-prion activity and significantly retarded survival times of the mice subsequently infected with Fukuoka-1 prions. These results might open a way for development of a new type of antigenic mimicry-based prion vaccine.
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Daisuke
D
Ishibashi
Hitoki
H
Yamanaka
Tsuyoshi
T
Mori
Naohiro
N
Yamaguchi
Yoshitaka
Y
Yamaguchi
Noriyuki
N
Nishida
Suehiro
S
Sakaguchi
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006867:Hydrolases / Q000008:administration & dosage / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D017096:Prion Diseases / Q000276:immunology / Q000517:prevention & control*; D011328:Prions / Q000008:administration & dosage* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology
D001323:Autoantibodies; D001426:Bacterial Proteins; D000939:Epitopes; D011328:Prions; D011994:Recombinant Proteins; D006867:Hydrolases; C109401:aruB protein, Pseudomonas aeruginosa