Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T cell type 2 profile.
Given the continued spread of human immunodeficiency virus (HIV)-1 worldwide, developing efficient vaccine strategies against HIV-1 is a key task. We tested the safety and immunogenicity of a multicomponent, cell-based vaccine that consisted of antigen-expressing apoptotic bodies with or without autologous dendritic cells (DCs). The vaccine strategy involved transfection of human 293T cells with codon-optimized DNA vectors expressing env of HIV1084i, a newly transmitted pediatric HIV-1 clade C strain; SHIV89.6P tat; and SIVmac239 gag-protease. Apoptotic bodies were generated by heat shock and ultraviolet irradiation and mixed either with mouse DCs (DC-cell vaccine) or given directly (cell-only vaccine) to BALB/c mice for initial priming; boosts consisted of apoptotic bodies only. The immunogens were well tolerated with or without DCs. Compared with the cell-only vaccine, the DC-cell vaccine induced higher antibody titers against all three antigens, whereas virus-specific cytotoxic T lymphocyte responses were equally strong in both groups. Iso-type analysis of viral antigen-specific antibodies revealed a skewing toward helper T type 2 responses induced by the DC-cell vaccine but not by the cell-only vaccine. In summary, both vaccine strategies were safe and induced cellular as well as humoral antiviral immunity; the DC-based approach had the advantage of significantly stronger antibody responses.
Gruber
Andreas
A
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Chalmers
Alistair S
AS
Rasmussen
Robert A
RA
Ong
Helena
H
Popov
Sergei
S
Andersen
Janet
J
Hu
Shiu-Lok
SL
Ruprecht
Ruth M
RM
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D014614:Vaccines, Synthetic