A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees.
Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long-term protection. Here we describe a new T-cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus. Suppression of acute viremia in vaccinated chimpanzees occurred as a result of massive expansion of peripheral and intrahepatic HCV-specific CD8(+) T lymphocytes that cross-reacted with vaccine and virus epitopes. These findings show that it is possible to elicit effective immunity against heterologous HCV strains by stimulating only the cellular arm of the immune system, and suggest a path for new immunotherapy against highly variable human pathogens like HCV, HIV or malaria, which can evade humoral responses.
Folgori
Antonella
A
Istituto di Ricerche di Biologia Molecolare P. Angeletti, via Pontina km30,600, 00040 Pomezia, Rome, Italy.
Capone
Stefania
S
Ruggeri
Lionello
L
Meola
Annalisa
A
Sporeno
Elisabetta
E
Ercole
Bruno Bruni
BB
Pezzanera
Monica
M
Tafi
Rosalba
R
Arcuri
Mirko
M
Fattori
Elena
E
Lahm
Armin
A
Luzzago
Alessandra
A
Vitelli
Alessandra
A
Colloca
Stefano
S
Cortese
Riccardo
R
Nicosia
Alfredo
A
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D018936:Hepatitis C Antigens / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology / Q000494:pharmacology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000939:Epitopes; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014761:Viral Hepatitis Vaccines