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- W2111487603 abstract "Although vaccines are important in preventing viral infections by inducing neutralizing antibodies (nAbs), HIV-1 has proven to be a difficult target and escapes humoral immunity through various mechanisms. We sought to test whether HIV-1 Env mimics may serve as immunogens.Using random peptide phage display libraries, we identified the epitopes recognized by polyclonal antibodies of a rhesus monkey that had developed high-titer, broadly reactive nAbs after infection with a simian-human immunodeficiency virus (SHIV) encoding env of a recently transmitted HIV-1 clade C (HIV-C). Phage peptide inserts were analyzed for conformational and linear homology using computational analysis; some peptides mimicked various domains of the original HIV-C Env, such as conformational V3 loop epitopes and the conserved linear region of the gp120 C-terminus. Next, we devised a novel prime/boost strategy to test the immunogenicity of such phage-displayed peptides and primed mice only once with HIV-C gp160 DNA followed by boosting with mixtures of recombinant phages.This strategy, which was designed to focus the immune system on a few Env epitopes (immunofocusing), not only induced HIV-C gp160 binding antibodies and cross-clade nAbs, but also linked a conserved HIV Env region for the first time to the induction of nAbs: the C-terminus of gp120. The identification of conserved antigen mimics may lead to novel immunogens capable of inducing broadly reactive nAbs." @default.
- W2111487603 created "2016-06-24" @default.
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- W2111487603 date "2008-12-15" @default.
- W2111487603 modified "2023-09-26" @default.
- W2111487603 title "Inducing Cross-Clade Neutralizing Antibodies against HIV-1 by Immunofocusing" @default.
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- W2111487603 doi "https://doi.org/10.1371/journal.pone.0003937" @default.
- W2111487603 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2597739" @default.
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