NDDIC News
DNA Vaccines and Antiviral Schemes: Fighting Hepatitis C
The 6th International Symposium on Hepatitis C & Related Viruses
Although 4 million Americans are infected with the hepatitis C virus
(HCV), a vaccine and effective treatment strategies remain elusive. At
this summer's 6th International Symposium on Hepatitis C & Related
Viruses, held at the National Institutes of Health, researchers discussed
DNA vaccines and antiviral methods for preventing and treating hepatitis
C.
DNA Vaccines
DNA vaccines, an emerging preventive tool, expose subjects to part of
the viral genome, instead of extracts of whole dead viruses, as is the
case with traditional vaccines. DNA vaccines have not been tested in humans,
but investigators have studied their effects in mice and primates. In
one study, researchers gave HLA-A2.1 mice a DNA vaccine that produces
HCV's core protein. They then injected the mice (as well as an unvaccinated
control group) with HCV core protein. At subsequent intervals of 6 days,
2 months, and 6 months, the immunized mice had significantly lower viral
titer than the mice in the control group. The investigators suggest that
a DNA vaccine expressing HCV core protein might give humans long-lasting
immunity to HCV.
Another study looked at the effectiveness of using a nonreplicating canarypox virus encoding the HCV gene to deliver the DNA vaccine to mice. This approach appears to diversify T-cell responses and enhance immune response to HCV proteins.
A study using primates is testing the effectiveness of vaccination with
plasmids containing either the E2 and p7 genes from HCV
or a shortened form of the E2 protein targeted to the cell surface (called
pE2surf). Preliminary results show a stronger humoral immune response
from the pE2surf.
Antiviral Development and Therapies
Researchers are also developing promising antiviral treatments. Some
of the gene therapies discussed at the meeting include
- Inhibiting the protease of HCV by using peptide carboxylic acids and
serine trap inhibitors.
- Using intracellular single-chain antibodies for gene ablation in chronic
HCV infection.
- Developing effective, but less toxic, ribavirin analogs.
- Using anti-HCV immunoglobulins in treatment.
Interferon alpha remains the mainstay of hepatitis C treatment, but researchers
continue to study interferon to determine its effects on viral levels
in the blood and liver, the most effective dose and dosing schedule, and
ways to combine it with other drugs to fight the disease, among other
questions.
In addition to vaccine and treatment strategies, the symposium also addressed
issues such as virus-cell interactions, pathogenesis and carcinogenesis,
epidemiology and natural history, model systems, and structural and nonstructural
proteins.
NIH Publication No. 00–4552
February 2000
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