Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2003-8-18
pubmed:abstractText
A novel synthetic peptide immunogen targeting the human immunodeficiency virus type-1 (HIV-1) coreceptor CXCR4 was evaluated for its capacity to induce CXCR4-specific antibodies with anti-HIV-1 activity in BALB/c mice and cynomolgus monkeys. A cyclic closed-chain dodecapeptide mimicking the conformation-specific domain of CXCR4 (cDDX4) was prepared in which Gly-Asp, as the dipeptide forming a spacer arm, links the amino and carboxyl termini of the decapeptidyl linear chain (linear DDX4, Asn176 to Ile185) derived from the undecapeptidyl arch (UPA; Asn176 to Cys186) of extracellular loop 2 (ECL-2) in CXCR4. Immunization of BALB/c mice with cDDX4 conjugated with a multiple-antigen peptide (cDDX4-MAP) induced conformational epitope-specific antibodies, and monoclonal antibody IA2-F9 reacted with cDDX4, but not with linear DDX4, as determined by real-time biomolecular interaction analysis using surface plasmon resonance. The antibody also reacted with cells expressing CXCR4 but not with cells expressing the other HIV coreceptor, CCR5. Furthermore, the antibody inhibited the replication of HIV-1 X4 virus (using CXCR4), as shown by an infection assay using both MAGIC-5 cells and MT4 cells, but not that of HIV-1 R5 virus (using CCR5). The antibody weakly interfered with chemotaxis induced by stromal cell-derived factor-1 alpha in THP-1 cells or moderately inhibited the chemotaxis of Molt4#8 cells under the same conditions. In addition, immunization of cynomolgus monkeys also induced cDDX4-specific antibodies with anti-HIV activity. Taken together, these results indicate that cDDX4 conjugated with a multi-antigen peptide induces the conformational epitope-specific antibodies to the undecapeptidyl arch of CXCR4 may be a novel candidate immunogen for preventing disease progression in HIV-1-infected individuals.
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
22
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32335-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12771150-AIDS Vaccines, pubmed-meshheading:12771150-Amino Acid Sequence, pubmed-meshheading:12771150-Animals, pubmed-meshheading:12771150-Chemotaxis, Leukocyte, pubmed-meshheading:12771150-Disease Progression, pubmed-meshheading:12771150-Female, pubmed-meshheading:12771150-HIV Infections, pubmed-meshheading:12771150-HIV-1, pubmed-meshheading:12771150-Macaca fascicularis, pubmed-meshheading:12771150-Mice, pubmed-meshheading:12771150-Mice, Inbred BALB C, pubmed-meshheading:12771150-Molecular Sequence Data, pubmed-meshheading:12771150-Neutralization Tests, pubmed-meshheading:12771150-Peptides, Cyclic, pubmed-meshheading:12771150-Receptors, CCR5, pubmed-meshheading:12771150-Receptors, CXCR4, pubmed-meshheading:12771150-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:12771150-Virus Replication
pubmed:year
2003
pubmed:articleTitle
A novel cyclic peptide immunization strategy for preventing HIV-1/AIDS infection and progression.
pubmed:affiliation
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto, 862-0973, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't