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The Recombinant Immunogen with High‐Density Epitopes of ELDKWA and ELDEWA Induced Antibodies Recognizing Both Epitopes on HIV‐1 gp41
Author(s) -
Wang Zuguang,
Liu Zuqiang,
Cheng Xiwen,
Chen YingHua
Publication year - 2005
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2005.tb03657.x
Subject(s) - epitope , immunogen , gp41 , linear epitope , monoclonal antibody , virology , biology , antibody , microbiology and biotechnology , epitope mapping , recombinant dna , biochemistry , immunology , gene
The high mutation rate of HIV‐1 (human immunodeficiency virus‐1) is a major obstacle to developing an effective vaccine. The mutation of ELDKWA‐ (aa669–674) to ELDEWA‐epitope on HIV‐1 gp41 caused the immune escape from neutralization by potent anti‐HIV‐1 human monoclonal antibody (mAb) 2F5. In this study, we suggested and evaluated a multi‐epitope vaccine as a new strategy to develop HIV‐1 vaccines. A glutathione S ‐transferase (GST) fusion protein (GST‐K 8 E 8 ) containing 8 copies of ELDKWA‐ and mutated ELDEWA‐epitopes was constructed and used to immunize mice or rabbits. Analysis of the antisera (rAS3) induced by GST‐K 8 E 8 suggested that multi‐epitope vaccine immunogen could raise antibodies in mice and rabbits against either the original ELDKWA‐epitope or the mutated ELDEWA‐epitope that resulted in immune escape. Briefly, ELDKWA‐epitope‐specific antibodies, directly purified from rAS3 by ELDKWA‐epitope‐peptide affinity chromatography, recognized either original gp41 protein (ELDKWA, rgp41K) or mutated gp41 (ELDEWA, rgp41E) in immunoblotting assay; in contrast, the existing ELDKWA‐epitope antibodies recognized only rgp41K but not rgp41E, which were purified by ELDKWA‐epitope‐peptide affinity chromatography from rAS3 that were firstly completely pre‐absorbed by ELDEWA‐epitope‐peptide affinity beads. And the same results were also observed when detecting the ELDEWA‐epitope‐specific antibodies in rAS3 by a means similar to the above. All the data presented here demonstrated that a high density multi‐epitope vaccine could be an interesting strategy against HIV‐1 mutation.