HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat.
Selection of potent yet low reactogenic adjuvants for protein immunization is important for HIV-1 vaccine development. Immunogenicity of electroporated DNA (HIV env) and recombinant gp120, administered with either QS-21 or the orally administered immunomodulator, Talabostat, was evaluated in BALB/c mice. Electroporation of low dose DNA elicited Th1 cytokines and anti-envelope antibodies. Immunization with gp120 protein alone with or without Talabostat elicited lower Th1 and Th2 cytokine levels but comparable anti-gp120 antibodies to QS-21-formulated protein. Boosting of DNA-primed mice with gp120/Talabostat induced similar anti-gp120 antibody titers and slightly higher levels of Th1 and Th2 cytokines relative to QS-21-formulated protein. Induction of CD8(+) and CD4(+) T cells and functional CTL activity was noted. These results highlight the potential use of orally administered Talabostat for efficient protein boosting of antibody and T-cell responses primed by DNA.
Cristillo
Anthony D
AD
Advanced BioScience Laboratories, Inc., 5510 Nicholson Lane, Kensington, MD 20895, USA.
Galmin
Lindsey
L
Restrepo
Susana
S
Hudacik
Lauren
L
Suschak
John
J
Lewis
Brad
B
Draghia-Akli
Ruxandra
R
Aziz
Nazneen
N
Weiss
Deborah
D
Markham
Phillip
P
Pal
Ranajit
R
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D001897:Boronic Acids / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D004151:Dipeptides / Q000008:administration & dosage*; D018274:Electroporation; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D001897:Boronic Acids; D016207:Cytokines; D004279:DNA, Viral; D004151:Dipeptides; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C514044:talabostat