title: HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120.
abstract: HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that suitably prepared envelope trimers have nearly all the antigenic properties expected for native viral spikes. These stable, rigorously homogenous trimers have antigenic properties markedly different from those of monomeric gp120s derived from the same sequences, and they induce potent neutralizing antibody responses for a cross-clade set of tier 1 and tier 2 viruses with titers substantially higher than those elicited by the corresponding gp120 monomers. These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development.
authors: Division of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.
authors: James M
authors: JM
authors: Kovacs
authors: Joseph P
authors: JP
authors: Nkolola
authors: Hanqin
authors: H
authors: Peng
authors: Ann
authors: A
authors: Cheung
authors: James
authors: J
authors: Perry
authors: Caroline A
authors: CA
authors: Miller
authors: Michael S
authors: MS
authors: Seaman
authors: Dan H
authors: DH
authors: Barouch
authors: Bing
authors: B
authors: Chen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D055503:Protein Multimerization / Q000276:immunology*; D020349:Surface Plasmon Resonance; D014461:Ultracentrifugation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C514793:gp120 protein, Human immunodeficiency virus 1; C097729:gp140 envelope protein, Human immunodeficiency virus 1