title: Receptor Binding by Cholera Toxin B-Subunit and Amino Acid Modification Improves Minimal Peptide Immunogenicity.
abstract: We increase our understanding of augmenting a cellular immune response, by using an HIV-1 protease-derived epitope (PR75-84), and variants thereof, coupled to the C-terminal, of the B subunit of cholera toxin (CTB). Fusion proteins were used for immunizations of HLA-A0201 transgenic C57BL/6 mice. We observed different capacities to elicit a cellular immune response by peptides with additions of five to ten amino acids to the PR epitope. There was a positive correlation between the magnitude of the elicited cellular immune response and the capacity of the fusion protein to bind GM-1. This binding capacity is affected by its ability to form natural pentamers of CTB. Our results suggest that functional CTB pentamers containing a foreign amino acid-modified epitope is a novel way to overcome the limited cellular immunogenicity of minimal peptide antigens. This way of using a functional assay as readout for improved cellular immunogenicity might become highly valuable for difficult immunogens such as short peptides (epitopes).
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 82 Stockholm, Sweden; Division of Education and Research administration, Mälardalen University, P.O. Box 883, 721 23 Västerås, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Boberg
authors.affiliation: Etvax AB, Gunnar Asplunds Alle 16, 171 63 Solna, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stålnacke
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 82 Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
authors.affiliation: Institution of Clinical and Experimental Medicine, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 82 Stockholm, Sweden.
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.affiliation: Etvax AB, Gunnar Asplunds Alle 16, 171 63 Solna, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Carlin