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=
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.
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.