title: Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1.
abstract: The core of the gp120 glycoprotein from human immunodeficiency virus type 1 (HIV-1) is comprised of three major structural domains: the outer domain, the inner domain, and the bridging sheet. The outer domain is exposed on the HIV-1 envelope glycoprotein trimer and contains binding surfaces for neutralizing antibodies such as 2G12, immunoglobulin G1b12, and anti-V3 antibodies. We expressed the outer domain of HIV-1(YU2) gp120 as an independent protein, termed OD1. OD1 efficiently bound 2G12 and a large number of anti-V3 antibodies, indicating its structural integrity. Immunochemical studies with OD1 indicated that antibody responses against the outer domain of the HIV-1 gp120 envelope glycoprotein are rare in HIV-1-infected human sera that potently neutralize the virus. Surprisingly, such outer-domain-directed antibody responses are commonly elicited by immunization with recombinant monomeric gp120. Immunization with soluble, stabilized HIV-1 envelope glycoprotein trimers elicited antibody responses that more closely resembled those in the sera of HIV-1-infected individuals. These results underscore the qualitatively different humoral immune responses elicited during natural infection and after gp120 vaccination and help to explain the failure of gp120 as an effective vaccine.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St., JFB 824, Boston, MA 02115, USA. joseph_sodroski@dfci.harvard.edu
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
authors.forename: Vesko
authors.initials: V
authors.lastname: Tomov
authors.forename: Svetla
authors.initials: S
authors.lastname: Kurteva
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Xinping
authors.initials: X
authors.lastname: Ren
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D008969:Molecular Sequence Data; D011817:Rabbits
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120