title: Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state.
abstract: The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against immunogens bearing these epitopes. Given that structural and biochemical studies suggest that the lipid membrane of the virion is involved in their proper configuration, HIV-1 gp41 derivatives in a pre-fusion state were expressed on the surface of immature virus like particles (VLP) derived from Sf9 cells. Guinea pigs were immunized with three doses of VLPs or Sf9 cells presenting gp41 derivatives with or without E. coli heat-labile enterotoxin (LT) as an adjuvant. While immune sera contained high titer anti-VLP antibodies, the specific anti-gp41 antibody responses were low with no neutralizing antibodies detected. An explanation for this absence may be the low level of gp41 expression relative to the many other proteins derived from host cells which are incorporated onto the VLP surface. In addition, the anti-gp41 immune response was preferentially directed to the C-helical domain, away from the MPER. Future vaccine design needs to contend with the complexity of epitope display as well as immunodominance.
authors.affiliation: Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Mikyung
authors.initials: M
authors.lastname: Kim
authors.forename: Zhisong
authors.initials: Z
authors.lastname: Qiao
authors.forename: Jessica
authors.initials: J
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006168:Guinea Pigs; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D020349:Surface Plasmon Resonance
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D000939:Epitopes; D015700:HIV Envelope Protein gp41