title: Role of human CD4 D1D2 domain in HIV-1 infection.
abstract: Broadly neutralizing antibodies and appropriate immunogens are critical for preexposure prophylaxis and therapeutic HIV vaccines. In this study, we aimed to explore effective antibodies against the genetically diverse HIV-1 strains by investigating the roles of human CD4 D1D2 domain and nonvariable immugens. The human CD4 D1D2 domain and the chimeric protein of mouse D1 domain/human D2 domain were expressed in Sf9 insect cells and purified by gel-filtration chromatography. The human CD4 D1D2 domain potently inhibited the infection of 77.8% HIV-1 pseudoviruses, including the clades AE, B' and BC, with less than 20 μg/mL of IC(50). pcDNA3.1-mhD1D2m and pcDNA3.1-mhD2m plasmids were used for the production of mouse anti-human CD4 polyclonal antibodies. The neutralizing activities of the polyclonal antibodies were determined by using pseudotyped HIV-1 viruses. The antibodies induced by plasmids containing human CD4 D1D2 domain were able to potently inhibit all pseudotyped HIV-1 strains. The antibodies from mhD1D2m-immunized mice also showed strong binding capacity to CD4 expressed on the surface of TZM-bl cells. The potent and broad inhibitory activity of antibodies against the human CD4 D1D2 domain may be used to develop effective passive immunization agent to control the spread of HIV infection.
authors.affiliation: Department of Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Lu
authors.forename: Senyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Jiang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Guanshi
authors.initials: G
authors.lastname: Wang
authors.forename: Weijun
authors.initials: W
authors.lastname: Zhu
authors.forename: Rongyue
authors.initials: R
authors.lastname: Lei
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology; D015704:CD4 Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D018411:Spodoptera
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies