CSL, Chiron move to Phase II hep C vaccine trial

The hopes of hundreds of thousands of people around the world chronically infected with hepatitis C virus could be riding on an Australian clinical trial of a new, potentially life-saving vaccine being jointly developed by US-based Chiron Corporation and Melbourne pharmaceutical company CSL (ASX:CSL).

CSL is giving Chiron's patented recombinant protein brew extra immunological fizz with its proprietary Iscomatrix adjuvant, a combination of phospholipid and cholesterol, formulated with a purified saponin extract from the bark of a South American tree Quillaja saponaria.

CSL and Chiron have already conducted a Phase I clinical trial in a group of volunteers in Australia, which confirmed the vaccine is well tolerated and generates strong antibody- and cell-mediated immune responses. Both are essential for an effective therapeutic vaccine, according to John Lambert, president of Chiron Vaccines.

The decision by Chiron and CSL to move into Phase II clinical trials in chronically infected HCV patients is a validation of CSL's Iscomatrix adjuvant technology, according to CSL.

CSL's chief scientific officer, Dr Andrew Cuthbertson, said the company had spent several years developing the adjuvant. Early trials in mice indicated it elicited an unusually potent, integrated immune response when used either with whole-virus or recombinant antigens.

The Phase I trial showed the adjuvant produces the same response in humans. Cuthbertson said conventional vaccines produced a strong antibody (humoral) response, but not the T-cell response required to identify and eliminate infected cells that serve as reservoirs of infection in chronic viral diseases like HCV. Vaccines containing Iscomatrix licit both helper-inducer (CD4) and cytotoxic (CD8) T-cell responses.

Chiron and CSL will begin a further clinical trial of the vaccine in chronically infected HCV patients in Australia this year, 14 years after Chiron researchers identified the infectious agent in what was then known as hepatitis non-A, non-B. It was the first virus to be identified from its cloned genetic blueprint, without first being isolated, cultured and characterised.

HCV is a blood-borne virus that commonly infects needle-sharing drug users. Tens of thousands of people who experimented briefly with injected drugs in the 1970s and 1980s became infected; many cleared the infection and suffered no ill-effects, but a small percentage developed chronic, potentially lethal liver infections.

The prototype HCV vaccine, if successful in eliminating the virus, would be one of the first vaccines developed primarily as a therapy for a chronic viral infection. Most vaccines are used to produce protective immunity in healthy individuals.

Cuthbertson said the Iscomatrix adjuvant-boosted HCV vaccine was at the vanguard of a new family of immunotherapeutics for treating chronic infectious diseases, and possibly cancer.

CSL's Iscomatrix is already being used to develop therapeutic vaccines against human papilloma virus (HPV) and cancer, the latter with the Ludwig Institute for Cancer Research in Melbourne.

"We're interested in applying this technology generically, to treat some of the big scourges, Cuthbertson said. "We believe it may be applicable to a number of nasty chronic or persistent infections, with the ultimate challenge being an effective treatment for HIV/AIDS and cancer."