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• W1982525636 abstract "ABSTRACT Single-chain derivatives of JRFL gp120 linked to the first two domains of human CD4 (gp120-CD4 D12 ) or to the CD4 miniprotein analog CD4M9 (gp120-M9), have been constructed. Biacore studies revealed that gp120-CD4 D12 and gp120-M9 bound to antibody 17b with dissociation constants of 0.8 and 25 nM, respectively, at pH 7.0, while gp120 alone did not bind. The binding of gp120-CD4 D12 to 17b is not affected by the addition of excess soluble CD4 D12 , while the binding of gp120-M9 is enhanced. This finding indicates that the M9 component of the single chain interacts relatively weakly with gp120 and can be displaced by soluble CD4 D12 . Immunogenicity studies of gp120, gp120-CD4 D12 , and gp120-M9 were carried out with guinea pigs. All three molecules were highly immunogenic. The resulting antisera were examined for neutralizing activities against various human immunodeficiency virus type 1 isolates. Broadly neutralizing activity was observed only with sera generated against gp120-CD4 D12 . These antisera were depleted of anti-CD4 D12 antibodies by being passed over a column containing immobilized CD4 D12 . The depleted sera showed a loss of broadly neutralizing activity. Sera that were affinity purified over a column containing immobilized gp120-M9 also lacked such neutralizing activity. This finding suggests that the broadly neutralizing response observed is exclusively due to anti-CD4 antibodies. Competition experiments showed that only antisera generated against gp120-CD4 D12 competed with the CD4 i antibody 17b and that this activity was not affected by depletion of anti-CD4 antibodies. The data indicate that although antibodies targeting the CD4 i epitope were generated by the gp120-CD4 D12 immunogen, these antibodies were nonneutralizing." @default.
• W1982525636 created "2016-06-24" @default.
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• W1982525636 date "2005-02-01" @default.
• W1982525636 modified "2023-09-30" @default.
• W1982525636 title "Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4_D12and gp120-M9: Implications for Targeting the CD4_iEpitope in Human Immunodeficiency Virus Vaccine Design" @default.
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• W1982525636 doi "https://doi.org/10.1128/jvi.79.3.1713-1723.2005" @default.
• W1982525636 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/544110" @default.
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