First hint of a hepatitis C vaccine?

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A novel vaccine, IC41, containing sections from the hepatitis C virus (HCV) has produced a modest, but apparently continuous, viral load decline in patients who already have hepatitis C.

Although this is a therapeutic rather than a preventative vaccine, this is the first time that any vaccine designed to enhance the body’s natural immune response to HCV has had a significant effect on viral load. Although the pegylated interferon in standard HCV treatment is an analogue of a protein made by the immune system, it has to be dosed continuously. IC41 produced a continuing drop in viral load 20 weeks after the last dose, and therefore may be acting like a true vaccine and establishing a long-term immune response to the hepatitis C virus.

The average viral load drop seen was modest, being cut by two-thirds (-0.47 logs). Patients with the highest initial HCV viral loads (over 2 million international units/ml) experienced viral load drops of more than 75% (-0.61 logs). Despite these falls being relatively small compared with the high viral load typical of HCV infection, they were highly statistically significant (p=

Glossary

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

hyper

Prefix meaning higher than usual.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

Fifty patients with HCV who had not taken treatment previously were randomised to two vaccination regimens, one of which worked while the other did not. The successful regimen consisted of eight shallow injections administered just inside the skin (intradermally) every two weeks. These were accompanied by topical application of the immune enhancing drug imiquimod (Aldara), which enhances the activity of the innate immune system and mobilises natural interferons, and is well known as a genital wart treatment.

The unsuccessful regimen consisted of 16 weekly injections given under the skin (subcutaneously) without imiquimod. This produced no reduction in viral load.

HCV viral load had already gone down by 40% by the end of the 16 weeks in recipients of the first regimen but appeared to continue to fall over the next 20 weeks, a result described by the researchers as ‘encouraging’. Significant drops in viral load started by the third vaccination in patients with high initial viral loads.

Although the viral load drops observed would not in themselves have much clinical significance, the success of HCV treatment is strongly related to initial viral load, and this therapeutic vaccine might serve as a way of enhancing other therapies.

It also demonstrates that it is possible to engineer an effective immune response against HCV, a virus whose hyper-variability is such that some researchers thought a vaccine could not work.

About half of the patients showed measurable T-cell responses to HCV up to six months after the course of vaccination. However these responses were not correlated with the viral load decrease and it is not known exactly what effective immune response IC41 is stimulating.

References

Klade CS et al. Significant continuous viral load decline in treatment-naive HCV genotype 1 patients after therapeutic peptide vaccination with IC41. American Association for the Study of Liver Disease (AASLD) Conference, Boston. Abstract 1558. 2009.