Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine.
While DNA vaccines have been shown to prime cellular immune responses, levels are often low in nonhuman primates or humans. Hence, efforts have been directed toward boosting responses by combining DNA with different vaccination modalities. To this end, a polyvalent DNA prime/protein boost vaccine, consisting of codon optimized HIV-1 env (A, B, C, E) and gag (C) and homologous gp120 proteins in QS-21, was evaluated in rhesus macaques and BALB/c mice. Humoral and cellular responses, detected following DNA immunization, were increased following protein boost in macaques and mice. In dissecting cellular immune responses in mice, protein-enhanced responses were found to be mediated by CD4+ and CD8+ T cells with a Th1 cytokine bias. Our study reveals that, in addition to augmenting humoral responses, protein boosting of DNA-primed animals augments cellular immune responses mediated by CD8+ CTL, CD4+ T-helper cells and Th1 cytokines; thus, offering much promise in controlling HIV-1 in vaccinees.
Cristillo
Anthony D
AD
Advanced BioScience Laboratories, Department of Cell Biology, 5510 Nicholson Lane, Kensington, MD 20895, USA. anthony.cristillo@ablinc.com
Wang
Shixia
S
Caskey
Michael S
MS
Unangst
Tami
T
Hocker
Lindsey
L
He
Leilei
L
Hudacik
Lauren
L
Whitney
Stephen
S
Keen
Tim
T
Chou
Te-Hui W
TH
Shen
Siyuan
S
Joshi
Swati
S
Kalyanaraman
Vaniambadi S
VS
Nair
Balachandran
B
Markham
Phillip
P
Lu
Shan
S
Pal
Ranajit
R
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D019444:Vaccines, DNA