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N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies.

Abstract
The Human immunodeficiency virus type 1 (HIV-1) gp41 membrane proximal external region (MPER) is targeted by broadly neutralizing antibodies (e.g. 2F5, 4E10, Z13e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However, these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope (amino acids (aa) 662-667 in the MPER) but also several other residues (aa 652-655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.
AuthorsDezhi Li, Jie Liu, Li Zhang, Tianshu Xu, Junheng Chen, Liping Wang, Qi Zhao
JournalVirologica Sinica (Virol Sin) Vol. 30 Issue 6 Pg. 449-56 (Dec 2015) ISSN: 1995-820X [Electronic] Netherlands
PMID26715302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp41
Topics
  • AIDS Vaccines (immunology)
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal (immunology)
  • Antibodies, Neutralizing (immunology)
  • Epitopes (immunology)
  • Flow Cytometry
  • HEK293 Cells
  • HIV Antibodies (immunology, isolation & purification)
  • HIV Envelope Protein gp41 (immunology)
  • HIV Infections (immunology, therapy)
  • HIV-1 (immunology)
  • Humans
  • Leukocytes, Mononuclear (immunology)
  • Mice
  • Molecular Sequence Data
  • Neutralization Tests
  • Sequence Alignment
  • Yeasts (genetics, immunology)

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