Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers.
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. Robust cross-subtype HIV-1 specific T cell responses were detected in IFN-gamma 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.
Wang
Shixia
S
Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Kennedy
Jeffrey S
JS
West
Kim
K
Montefiori
David C
DC
Coley
Scott
S
Lawrence
John
J
Shen
Siyuan
S
Green
Sharone
S
Rothman
Alan L
AL
Ennis
Francis A
FA
Arthos
James
J
Pal
Ranajit
R
Markham
Phillip
P
Lu
Shan
S
D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D003429:Cross Reactions; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D007371:Interferon-gamma