title: The recombinant immunogen with high-density epitopes of ELDKWA and ELDEWA induced antibodies recognizing both epitopes on HIV-1 gp41.
abstract: 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-K8E8) 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-K8E8 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.
authors.affiliation: Protein Science Laboratory of the Ministry of Education, Laboratory of Immunology, Department of Biology, Tsinghua University, Beijing, P.R. China.
authors.forename: Zuguang
authors.initials: Z
authors.lastname: Wang
authors.forename: Zuqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiwen
authors.initials: X
authors.lastname: Cheng
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D014760:Viral Fusion Proteins