title: Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers.
abstract: An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNgamma ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.
authors.affiliation: Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Kim
authors.initials: K
authors.lastname: West
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Scott
authors.initials: S
authors.lastname: Coley
authors.forename: John
authors.initials: J
authors.lastname: Lawrence
authors.forename: Siyuan
authors.initials: S
authors.lastname: Shen
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Phillip
authors.initials: P
authors.lastname: Markham
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D019444:Vaccines, DNA; C514793:gp120 protein, Human immunodeficiency virus 1; D007371:Interferon-gamma