Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses.
We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55(gag) virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLP(A)s). The HIV-VLP(A)s show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4(+) T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLP(A)s in vivo.
Buonaguro
L
L
Laboratory of Viral Oncogenesis and Immunotherapies, and AIDS Reference Center, Istituto Nazionale Tumori Fondazione G. Pascale, Via Mariano Semmola 1, 80131 Naples, Italy.
Tornesello
M L
ML
Tagliamonte
M
M
Gallo
R C
RC
Wang
L X
LX
Kamin-Lewis
R
R
Abdelwahab
S
S
Lewis
G K
GK
Buonaguro
F M
FM
D000199:Actins / Q000737:chemistry; D016367:Baculoviridae / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D003713:Dendritic Cells / Q000821:virology*; D004705:Endocytosis; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D015398:Signal Transduction; D018417:Th1 Cells / Q000821:virology; D018418:Th2 Cells / Q000821:virology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000199:Actins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4