Antibodies to a nonconjugated prion protein peptide 95-123 interfere with PrP( Sc ) propagation in prion-infected cells.
1. Vaccination-induced anti-prion protein antibodies are presently regarded as a promising approach toward treatment of prion diseases. Here, we investigated the ability of five peptides corresponding to three different regions of the bovine prion protein (PrP) to elicit antibodies interfering with PrP(Sc) propagation in prion-infected cells.2. Rabbits were immunized with free nonconjugated peptides. Obtained immune sera were tested in enzyme-linked immunosorbent assay (ELISA) and immunoblot for their binding to recombinant PrP and cell-derived pathogenic isoform (PrP(Sc)) and normal prion protein (PrP(c)), respectively. Sera positive in all tests were chosen for PrP(Sc) inhibition studies in cell culture.3. All peptides induced anti-peptide antibodies, most of them reacting with recombinant PrP. Moreover, addition of the serum specific to peptide 95-123 led to a transient reduction of PrP(Sc) levels in persistently prion-infected cells.4. Thus, anti-PrP antibodies interfering with PrP(Sc) propagation were induced with a prion protein peptide nonconjugated to a protein carrier. These results point to the potential application of the nonconjugated peptide 95-123 for the treatment of prion diseases.
Oboznaya
Maria B
MB
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, GSP Moscow, Russia, oboznaya@mail.ru
Gilch
Sabine
S
Titova
Maia A
MA
Koroev
Dmitry O
DO
Volkova
Tatyana D
TD
Volpina
Olga M
OM
Schätzl
Hermann M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000915:Antibody Affinity; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D018620:PrPSc Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D017096:Prion Diseases / Q000276:immunology / Q000628:therapy* / Q000635:transmission*; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D017186:Titrimetry; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011994:Recombinant Proteins