Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2001-8-6
pubmed:abstractText
Peptide mimetics may substitute for carbohydrate antigens in vaccine design applications. At present, the structural and immunological aspects of antigenic mimicry, which translate into immunologic mimicry, as well as the functional correlates of each, are unknown. In contrast to screening peptide display libraries, we demonstrate the feasibility of a structure-assisted vaccine design approach to identify functional mimeotopes. By using concanavalin A (ConA), as a recognition template, peptide mimetics reactive with ConA were identified. Designed peptides were observed to compete with synthetic carbohydrate probes for ConA binding, as demonstrated by enzyme-linked immunosorbent assay and isothermal titration calorimetry (ITC) analysis. ITC measurements indicate that a multivalent form of one particular mimetic binds to ConA with similar affinity as does trimannoside. Splenocytes from mimeotope-immunized mice display a peptide-specific cellular response, confirming a T-cell-dependent nature for the mimetic. As ConA binds to the Envelope protein of the human immunodeficiency virus, type 1 (HIV-1), we observed that mimeotope-induced serum also binds to HIV-1-infected cells, as assessed by flow cytometry, and could neutralize T-cell line adapted HIV-1 isolates in vitro, albeit at low titers. These studies emphasize that mimicry is based more upon functional rather than structural determinants that regulate mimeotope-induced T-dependent antibody responses to polysaccharide and emphasize that rational approaches can be employed to develop further vaccine candidates.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30490-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11384987-Amino Acid Sequence, pubmed-meshheading:11384987-Animals, pubmed-meshheading:11384987-Antigens, pubmed-meshheading:11384987-Binding, Competitive, pubmed-meshheading:11384987-Binding Sites, pubmed-meshheading:11384987-Biochemistry, pubmed-meshheading:11384987-Calorimetry, pubmed-meshheading:11384987-Carbohydrate Sequence, pubmed-meshheading:11384987-Carbohydrates, pubmed-meshheading:11384987-Cell Division, pubmed-meshheading:11384987-Cell Separation, pubmed-meshheading:11384987-Concanavalin A, pubmed-meshheading:11384987-Dose-Response Relationship, Drug, pubmed-meshheading:11384987-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:11384987-Epitope Mapping, pubmed-meshheading:11384987-Flow Cytometry, pubmed-meshheading:11384987-Kinetics, pubmed-meshheading:11384987-Ligands, pubmed-meshheading:11384987-Mice, pubmed-meshheading:11384987-Mice, Inbred BALB C, pubmed-meshheading:11384987-Models, Molecular, pubmed-meshheading:11384987-Molecular Sequence Data, pubmed-meshheading:11384987-Peptides, pubmed-meshheading:11384987-Protein Conformation, pubmed-meshheading:11384987-Protein Structure, Secondary, pubmed-meshheading:11384987-Sequence Homology, Amino Acid, pubmed-meshheading:11384987-Spleen, pubmed-meshheading:11384987-Thermodynamics, pubmed-meshheading:11384987-Vaccines
pubmed:year
2001
pubmed:articleTitle
Directing the immune response to carbohydrate antigens.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.