ELNKWA-epitope specific antibodies induced by epitope-vaccine recognize ELDKWA- and other two neutralizing-resistant mutated epitopes on HIV-1 gp41.
Based on the fact that monoclonal antibody (mAb) 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 separately or in combination with other mAbs showed potent neutralizing activity to a wide range of primary HIV-1 isolates in vivo and in vitro, but this epitope undergoes restricted mutation. ELNKWA is a neutralizing-resistant mutated epitope. We induced ELNKWA-epitope-specific polyclonal and monoclonal antibodies and studied the interaction of the antibodies with ELDKWA-epitope and other two neutralizing-resistant mutated epitopes. The candidate ELNKWA-epitope-vaccine induced a high level of antibodies to the ELNKWA-epitope-peptide. The ELNKWA-epitope-specific polyclonal antibodies bound not only the ELNKWA-, but also ELDKWA-, ELEKWA- and ELDEWA-epitope-peptides in ELISA-assay. Moreover, the antibodies also recognized four C-domain-peptides (P5, P6, P7, P8) which contain these four epitopes, respectively. Interestingly, an ELNKWA-epitope-specific monoclonal antibody (TH-Ab1) induced by the candidate ELNKWA-epitope-vaccine could also recognize the four C-domain-peptides containing ELNKWA-, ELDKWA-, ELEKWA- and ELDEWK-epitopes. These results indicate that the candidate ELNKWA-epitope-vaccine could induce high levels of antibodies, which recognize the neutralizing epitope ELDKWA and three neutralizing-resistant mutated epitopes, suggesting that the candidate ELNKWA-epitope-vaccine may help to overcome the problem of viral escape from neutralization through mutation at D or K position, and may be developed as an effective vaccine with a broad neutralizing activity against HIV-1.
Dong
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XN
Laboratory of Immunology, Research Centre for Medical Science and Department of Biological Science and Technology, Tsinghua University, 100084, Beijing, People's Republic of China.
Xiao
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Y
Chen
Y H
YH
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009154:Mutation; D009500:Neutralization Tests; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D014614:Vaccines, Synthetic