Michael Houghton, Ph.D., Canada Excellence in Research Chair and Professor, Medical Microbiology & Immunology, University of Alberta
"We can be optimistic about HCV vaccine development based on 1) the demonstration of significant natural immunity in the chimpanzee challenge model and in man, 2) the identification of cellular and humoral correlates of immunity, 3) the demonstration of vaccine efficacy in the chimpanzee challenge model & 4)
the recent demonstration of a vaccine able to elicit broadly cross-neutralising antibodies against all major, global genotypes. Current vaccine candidates in clinical development elicit either broad,
cross-reactive cellular immune responses or broad,
cross-neutralizing antibody responses but combining both is likely to result in at least a partially effective vaccine against this highly heterogeneous virus that is estimated to infect many hundreds of thousands each year around the globe. "
Example
Candidate HCV vaccines have shown limited efficacy in clinical trials. Neutralizing antibodies (NAbs) are a key component of all licensed vaccines. In HCV infection,
NAbs are primarily directed to the major surface glycoprotein E2 and have been correlated with viral clearance. However, most HCV specific NAbs are directed to the hypervariable region 1 (HVR1), which are type-specific as the name suggests. By contrast, NAbs directed to the HCV receptor (CD81) binding site show the capacity to mediate broad neutralization, but these antibodies are rarely produced in the presence of the immunodominant HVR1. We have investigated how different oligomeric forms of Δ123 E2 (monomer, dimer and higher order forms) induce different levels of neutralizing antibodies.
http://www.imvacs.com/novel-vaccinesOxford study
""Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (
genotypes 1A and 3A)."
""The outside shell of the hepatitis C virus is very variable but the
inside of the virus is much more stable. That's where the engine of the virus is, where we may be able to successfully target many of the crucial pieces of machinery."
Choosing a more constant
internal virus part as a target would also stimulate a different type of immune response from what had been attempted in previous studies to develop an HCV vaccine.
..
we need T cells and
not antibodies to be able to react to the
inner components of the virus," said Klenerman."
Canada
"Houghton, also the Li Ka Shing Chair in Virology at the University of Alberta, says the vaccine, developed from a single strain,
has shown to be effective against all known strains of the virus. It took more than 10 years to develop and started while he was working for the drug company Novartis. Following previous vaccine tests funded by the National Institutes of Health that yielded promising results, he said there remained two critical questions."
"The challenge, Houghton said, was that hepatitis C is more virulent than HIV, thus coming up with a vaccine that would neutralize the different strains around the world was believed to be impossible.
Using a vaccine developed and tested on humans in his University of Alberta lab, Houghton and his co-investigator John Law discovered that
the vaccine was capable of eliciting broad cross-neutralizing antibodies against all the different major strains. Houghton says that this finding bodes good news for those with hep C and those who live or travel to areas where the disease is prevalent."
http://www.hepctrust.org.uk/News_Resour ... +C+VaccinePlease do link the studies
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