Perspectives for a hepatitis C virus vaccine

Background: Natural hepatitis C virus (HCV) infection elicits poor immunity. Although HCV proteins elicit immune responses in virtually all cases of infection, the great majority of HCV infections become chronic. Currently, no vaccine is available for HCV despite an estimated incidence of approximately 50 000 new cases per year in the USA alone.

Objectives: To discuss how the problems associated with developing a vaccine against HCV infection may be overcome and describe recent progress made towards overcoming these problems and developing a vaccine.

Study design: A cytofluorimetric assay that can assess the ability of a serum sample to neutralise the binding of the HCV-envelope glycoprotein E2 to human cells (neutralisation of binding or NOB assay) was developed. The assay was used to assess the levels of antibodies capable of neutralising E2 binding in the sera of vaccinated and carrier chimpanzees.

Results: Low titres of NOB antibodies were found in the majority of chimpanzees challenged with HCV infection. Chimpanzees immunised with the E1/E2 heterodimer developed NOB antibodies and high levels of neutralising antibodies. These chimpanzees were not protected from challenge with heterologous virus but were protected from subsequent chronic infection.

Conclusions: A subunit vaccine composed of recombinant HCV proteins may protect from infection or chronic infection by different HCV genotypes.