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. 2015 Dec 21;30(6):449–456. doi: 10.1007/s12250-015-3664-6

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

Dezhi Li 1,2, Jie Liu 2, Li Zhang 2, Tianshu Xu 2,3, Junheng Chen 2,3, Liping Wang 3,✉, Qi Zhao 2,4,✉
PMCID: PMC8200909  PMID: 26715302

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. graphic file with name 12250_2015_3664_Figa_HTML.jpg

Keywords: HIV-1, membrane proximal external region (MPER), 2F5, neutralizing antibody, yeast display

Footnotes

ORCID: 0000-0002-5969-6407

ORCID: 0000-0003-4308-5799

Contributor Information

Liping Wang, Phone: +86-431-85155348, Email: wanglp@jlu.edu.cn.

Qi Zhao, Phone: +86-755-86585201, Email: zhaoqi@alumni.cuhk.net.

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