Science

Dendritic cell-based hepatitis C vaccine effective in mouse tumor model

Last Updated: 2006-03-23 16:57:19 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - A dendritic cell-based hepatitis C virus (HCV) vaccine is effective in a mouse tumor challenge model, according to a report in the February issue of Gastroenterology.

"There are powerful new strategies being developed for HCV vaccines," Dr. Jack R. Wands from Brown University, Providence, Rhode Island told Reuters Health. "These approaches are encouraging with respect to generating long-lasting immune responses and could be used for immunotherapeutic or preventive treatment of HCV infection."

Dr. Wands and colleagues transduced mature dendritic cells with recombinant HCV core or nonstructural 5 (NS5) protein in vitro and in a tumor challenge model in mice.

Vaccination with HCV core-transduced dendritic cells induced cytotoxic T-lymphocytes, the authors report, but failed to produce significant quantities of antigen-specific cytokines.

In contrast, the results indicate, vaccination with NS5-transduced dendritic cells induced both antigen-specific cytotoxic T lymphocytes and T-helper 1-type CD4 T-cell responses.

The responses in mice immunized with NS5-transduced dendritic cells persisted for at least 10 weeks after inoculation, the researchers note.

The sustained antiviral response to NS5 was further evidenced by significantly reduced growth of NS5-expressing tumor cells inoculated into mice 10 weeks after vaccination, the report indicates.

"We are very excited about the possibility of using this approach as an immunotherapeutic strategy for individuals with persistent HCV infection," Dr. Wands said. "If such cellular immune responses to HCV can be activated and sustained, it is likely that by reducing viral load with standard therapy with pegylated interferon and ribavirin, it may be possible to eradicate low-level infection by stimulating the cellular immune responses through dendritic cell vaccination. This approach is also ideal as a prophylactic vaccine."

"To extend this vaccination approach for HCV to human biology and disease, we are now developing targeted approaches to deliver HCV structural and non-structural proteins to dendritic cells in vivo using a carrier system," Dr. Wands added. Such studies are in pre-clinical stages.

"Many research groups and companies are working on developing vaccines, but most experts do not expect an effective HCV vaccine on the market for many years, making the exploration of new vaccine candidates essential," Dr. Marie Larsson from Linkoping University in Sweden writes in a related editorial. "In order to develop an effective HCV vaccine, the vaccine researchers must learn more about why this infection is cleared in some of the people infected, whereas it becomes a chronic infection in others."

Gastroenterology 2006;130:453-464,603-606.