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Aug 25, 2011
 |  BC Innovations  |  Targets & Mechanisms

More than one way to stop HCV

A French team led byEpixis S.A. has developed an HCVvaccine that triggers both a T cell response and broadly neutralizing antibodies in macaques.1 Because of the ability to elicit both types of immune responses, the vaccine could have advantages over other HCV vaccines in development that focus only on T cell responses or that elicit neutralizing antibodies that do not attack the multiple genotypes of HCV.

Six companies have HCV vaccines in early stage clinical trials (see "HCV vaccines in clinical development").

HCV is difficult to neutralize because there are at least six distinct genotypes with more than 50 known subtypes. Genotypes 1a, 1b, 2b and 3a are the most common in the U.S., but even in a single infected individual, the virus is not homogeneous.

Epixis' vaccine has three components based on HCV genotype 1a: an adenovirus vector that produces HCV envelope protein E1 (E1) and E2, which elicit T cell responses, and two virus-like particles (VLPs) that present those proteins to the immune system and trigger antibody responses (see "Virus-like particles for HCV vaccine regimen").

The company first immunized macaques with the adenovirus vector to prime the immune system, followed by a boost with the two VLPs. This regimen provided T cell responses and antibody production against both HCV envelope proteins.

Next they showed cross-neutralization activity of the antibodies by using two types of in vitro assays based either on HCV pseudoparticles or cell culture-adapted HCV. Whereas HCV pseudoparticles mimic the early infection steps of HCV, making them useful for evaluating antibodies that neutralize virus entry, cell culture-adapted HCV goes through all stages of the virus' life cycle, allowing the evaluation of which...

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