Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates.
Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-gamma ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-gamma+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV.
Capone
Stefania
S
Istituto di Ricerche di Biologia Molecolare, P. Angeletti, Rome, Italy.
Zampaglione
Immacolata
I
Vitelli
Alessandra
A
Pezzanera
Monica
M
Kierstead
Lisa
L
Burns
Janine
J
Ruggeri
Lionello
L
Arcuri
Mirko
M
Cappelletti
Manuela
M
Meola
Annalisa
A
Ercole
Bruno Bruni
BB
Tafi
Rosalba
R
Santini
Claudia
C
Luzzago
Alessandra
A
Fu
Tong-Ming
TM
Colloca
Stefano
S
Ciliberto
Gennaro
G
Cortese
Riccardo
R
Nicosia
Alfredo
A
Fattori
Elena
E
Folgori
Antonella
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D003062:Codon / Q000008:administration & dosage / Q000276:immunology; D018274:Electroporation; D005260:Female; D018014:Gene Transfer Techniques; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D002679:Pan troglodytes; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D003062:Codon; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase