Human immunodeficiency virus-like particles activate multiple types of immune cells.
The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses.
Sailaja
Gangadhara
G
Emory Vaccine Center and Department of Microbiology and Immunology, Rollins Research Center 3086, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
Skountzou
Ioanna
I
Quan
Fu-Shi
FS
Compans
Richard W
RW
Kang
Sang-Moo
SM
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics; D015752:Genes, env; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis; D037181:Lectins, C-Type; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018411:Spodoptera / Q000166:cytology; D022721:Vaccines, Virosome / Q000276:immunology*; D022701:Virosomes / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
D016915:AIDS Vaccines; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D019041:L-Selectin; D037181:Lectins, C-Type; D008565:Membrane Proteins; D022721:Vaccines, Virosome; D022701:Virosomes; D051941:fms-Like Tyrosine Kinase 3; D000099192:CD69 Antigens; C084881:flt3 ligand protein; C497970:FLT3 protein, human