title: An antigenic HIV-1 peptide sequence engineered into the surface structure of transferrin does not elicit an antibody response.
abstract: One novel approach for the biological delivery of peptide drugs is to incorporate the sequence of the peptide into the structure of a natural transport protein such as human serum transferrin (HST). However, a potential drawback is that the HST may increase the immunoreactivity of the peptide, in the same way that carrier proteins can be used to generate highly immunogenic peptide hapten conjugates. In this study we have generated a recombinant HST carrier protein that contains a peptide substrate of HIV-1 protease (VSQNYPIVL). The protein retained native HST function, and the peptide was surface exposed since it was immunoreactive in native dot blots, and was cleaved by HIV-1 protease. Immunisation of rabbits with the recombinant protein elicited only a very poor anti-peptide immune response. In contrast, strong anti-peptide immune responses were raised against both the peptide alone, and a chemical conjugate of the peptide with HST. These data demonstrate that it is possible to attenuate the immune response normally directed against an immunogenic peptide sequence by engineering into a surface exposed loop of HST. These findings may have an important impact on the future design of peptide delivery systems.
authors.affiliation: Novartis Research Institute, Brunnerstrasse 59, A-1230, Vienna, Austria.
authors.forename: S A
authors.initials: SA
authors.lastname: Ali
authors.forename: H C
authors.initials: HC
authors.lastname: Joao
authors.forename: F
authors.initials: F
authors.lastname: Hammerschmid
authors.forename: J
authors.initials: J
authors.lastname: Eder
authors.forename: A
authors.initials: A
authors.lastname: Steinkasserer
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D014168:Transferrin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D014614:Vaccines, Synthetic