Linked Life Data

17306322

Source:http://linkedlifedata.com/resource/pubmed/id/17306322

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-5-8
pubmed:abstractText
Elicitation of broadly cross-reactive neutralizing antibodies (bcnAbs) in HIV infections is rare. To test the hypothesis that such antibodies could be elicited by HIV envelope glycoproteins (Envs) with unusual immunogenic properties and to identify novel bcnAbs, we used a soluble Env ectodomain (gp140) from a donor (R2) with high level of bcnAbs as an antigen for panning of an immune phage-displayed antibody library. The panning with the R2 Env resulted in significantly higher number of cross-reactive antibody clones than by using Envs from two other isolates (89.6 and IIIB). Two of the identified human monoclonal antibodies (hmAbs), m22 and m24, had sequences, neutralizing and binding activities similar or identical to those of the gp120-specific bcnAbs m18 and m14. The use of the R2 Env but not other Envs for panning resulted in the identification of a novel gp41-specific hmAb, m46. For several of the tested HIV-1 primary isolates its potency on molar basis was comparable to that of T20. It inhibited entry of primary isolates from different clades with an increased activity for cell lines with low CCR5 surface concentrations. The m46 neutralizing activity against a panel of clade C isolates was significantly higher in an assay based on peripheral blood mononuclear cells (4 out of 5 isolates were neutralized with an IC(50) in the range from 1.5 to 25 microg/ml) than in an assay based on a cell line with relatively high concentration of cell-surface-associated CCR5. In contrast to 2F5 and Z13, this antibody did not bind to denatured gp140 and gp41-derived peptides indicating a conformational nature of its epitope. It bound to a 5-helix bundle but not to N-heptad repeat coiled coils and a 6-helix bundle construct indicating contribution of both gp41 heptad repeats to its epitope and to a possible mechanism of neutralization. These results indicate that the R2 Env may contain unique exposed conserved epitopes that could contribute to its ability to elicit broadly cross-reactive antibodies in animals and humans; the newly identified antibodies may help in the development of novel vaccine immunogens and therapeutics.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-10221533, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-10580407, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11134278, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11153085, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11229405, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11244037, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11602729, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11788027, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11818487, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11836401, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-11997472, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-12088685, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-12209139, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-12584337, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-12644702, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-12646921, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-14659896, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-15039757, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-15219551, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-15308718, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-15542675, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-15731230, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-16051804, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-16216270, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-16378633, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-16904645, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-17078964, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-7546904, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-7973652, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-8537683, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-9060620, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-9129066, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-9451972, http://linkedlifedata.com/resource/pubmed/commentcorrection/17306322-9525605
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
363
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-90
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
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