title: Antigenic properties of peptide mimotopes of HIV-1-associated carbohydrate antigens.
abstract: The glycan shield of the human immunodeficiency virus (HIV) envelope protein presents many potential epitopes for vaccine development. To augment immune responses to HIV, type 1 (HIV-1), envelope-associated carbohydrate antigens, we are defining peptide mimics of HIV-associated carbohydrate antigens that function as antigen mimotopes that upon immunization will induce antibodies cross-reactive with carbohydrate antigens. We have previously defined peptides with a putative sequence tract RYRY that mimic concanavalin A-binding glycans. To imitate the multivalent binding of carbohydrates, we compared the avidity of a linear (911) and cyclic peptide (D002) reactive with concanavalin A presented in a multiple antigen peptide (MAP) format. The affinity of the MAP-D002 peptide was higher than that of the peptide MAP-911, whereas the avidity of D002 peptide was lower than that of 911. Serum from mice immunized with MAP-911 had lower titer for oligomannose-9 than those elicited by MAP-D002 under the same conditions, but both immunogens elicited antibodies that can block the binding of GP120 to dendritic cells. Antibodies that bind to the studied MAPs were found in a preparation of normal human immunoglobulin for intravenous use. Those that were purified on 911 bound back to 911 and D002, whereas anti-D002 antibodies were specific only for D002. Human antibodies reactive with both mimotopes and with a mannosyl preparation were observed to bind to envelope protein. These results suggested the potential to fine-tune the antibody response to carbohydrate antigens by modifying structural features of peptide mimotope-based immunogens.
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Anastas
authors.initials: A
authors.lastname: Pashov
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canziani
authors.forename: Behjatolah
authors.initials: B
authors.lastname: Monzavi-Karbassi
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Stewart
authors.initials: S
authors.lastname: Macleod
authors.forename: Rinku
authors.initials: R
authors.lastname: Saha
authors.forename: Marty
authors.initials: M
authors.lastname: Perry
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Vancott
authors.forename: Thomas
authors.initials: T
authors.lastname: Kieber-Emmons
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000737:chemistry; D015374:Biosensing Techniques; D002241:Carbohydrates / Q000737:chemistry*; D003208:Concanavalin A / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015488:HIV Antigens / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007700:Kinetics; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D002241:Carbohydrates; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D010455:Peptides; D011134:Polysaccharides; D011994:Recombinant Proteins; D003208:Concanavalin A; D008358:Mannose