Reuters Health Information (2006-02-06): Hepatitis C vaccine induces cellular immunity in chimpanzees
Drug & Device Development
Hepatitis C vaccine induces cellular immunity in chimpanzees
Last Updated: 2006-02-06 15:20:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Researchers in Italy have developed a vaccine against hepatitis C (HCV) that induces cross-reactive cellular immunity when administered to chimpanzees, the research team reports in Nature Medicine published online on February 5.
A previously developed HCV vaccine candidate induced neutralizing antibodies that were specific to only one strain and did not lead to any cellular immunity, the authors note.
The vaccine devised by Dr. Alfredo Nicosia and colleagues, at Istituto di Ricerche di Biologia Molecolare "P. Angeletti" in Rome, is a replication-deficient adenovirus electroporated with plasmid DNA coding for the HCV nonstructural region. They note that the nonstructural region comprises about two-thirds of the entire HCV polyprotein and contains large number of previously mapped T-cell epitopes.
When they immunized five chimpanzees with the vaccine, a fully functional T-cell response was observed, with all five developing CD4+ and CD8+ cell proliferative responses to HCV antigens. All vaccinees also developed HCV-specific intrahepatic CD8+ T cells.
Exposure of peripheral blood mononuclear cells to different viral strains showed that cells from four of the five vaccinated animals exhibited a potent cross-reactive CD8+ T cell response.
The authors then exposed the chimpanzees to an HCV challenge at week 49. Compared with control animals, the vaccinees had a markedly blunted peak of viremia that was more than 100 times lower than in the control group (p = 0.009). Four of the immunized animals cleared the virus within 1 to 7 weeks. In contrast, two of the control animals developed chronic persistent infections.
The animals that were immunized also rapidly expanded their CD8+ interferon-gamma+ T lymphocytes between weeks 51 and 55, coinciding or immediately preceding the drop in viral titers. And in contrast to the control animals, the vaccinated group exhibited no increase in hepatic enzymes.
"Induction of effective immunity against an HCV isolate with notable sequence diversity from our vaccine holds great promise for developing a T-cell HCV vaccine with potential for protection against different strains," Dr. Nicosia's group maintains.
They also suggest that similar vaccines can be developed to provide immunotherapy against HIV, tuberculosis or malaria, which can evade humoral responses to establish chronic infections.
Nature Med 2006.