title: 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.
authors.affiliation: School of Life Sciences, Xiamen University, Fujian, 361102, China.|Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Li
authors.affiliation: Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Xu
authors.affiliation: Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Junheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China. wanglp@jlu.edu.cn.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Fully Human Antibody Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, 518055, China. zhaoqi@alumni.cuhk.net.|Faculty of Health Sciences, University of Macau, Macau, China. zhaoqi@alumni.cuhk.net.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D015003:Yeasts / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41
keywords: 2F5; HIV-1; membrane proximal external region (MPER); neutralizing antibody; yeast display