Nobel Prize Laureate Michael Houghton, PhD, discusses the arduous journey to find the virus and a subsequent investigational vaccine designed to prevent hepatitis C (HCV).
For scientists trying to identify viruses, it can be a long and laborious process. It took Michael Houghton, PhD, and his fellow researchers over 7 years to discover the hepatitis C virus. Houghton says you typically need to have a “critical observation” in order to discover infectious pathogens like they did for both HBV and HIV.
“Once you can observe a protein, a virus, or a cell culture system associated with the pathogen, that gives you the molecular tool to lead to a full characterization of the virus,” Houghton said.
However, for Houghton and his colleagues they ended up not finding success going those routes and instead used a novel proteomics approach to discover HCV. The cloning process proved challenging, and during this time in the 1980s, proteomics was very early in the field, and Houghton used recombinant bacteria to clone everything and “taking the calculated gamble that there would be antibodies circulating. When you put the two together you get a lot of positives and have to sift through those positives to find one that you can convince yourselves is from hepatitis C.”
The arduous process was worth it as Houghton who is Li ka Shing professor and holder of the Canada Excellence in Research chair (CERC) in Virology within the Li Ka Shing Institute of Virology at the University of Alberta, codiscovered the hepatitis C virus along with Qui-Lim Choo, PhD, George Kuo, PhD, and Daniel W. Bradley, PhD. For the HCV discovery, Houghton was awarded the 2020 Nobel Prize in Physiology or Medicine and shared the honor with Harvey J. Alter, MD, and Charles M. Rice, PhD.
Along with the HCV discovery, Houghton and co-investigators performed studies that identified hepatitis C antibodies in the blood, which led to the development of subsequent blood tests for the virus, identified new drug targets and were also able to link HCV to liver cancer.
Vaccine Development: An Equally Difficult Path to Discovery
More recently, Houghton and a team of scientists developed a HCV vaccine which will be going into clinical trials in 2023.
The path from virus discovery to vaccine development was not any easier. For the vaccine, he encountered a number of issues including the lack of animal models, the challenge of growing cell cultures, and limited interest from biopharmaceutical companies on developing it.
Despite these challenges and shortcomings, Houghton and colleagues pushed on. After more than 10 years, he and his team at the University of Alberta developed what he calls a second generation vaccine. “We know it can elicit cross-neutralizing antibodies across most of the strains seen around the world…And then we have also dialed in cellular immune responses rather like the COVID-19 vaccines that do both—antibodies and cellular T-cell responses.” The last thing he points out is that they did some earlier vaccine studies in chimpanzees years ago which showed animal efficacy, and that no other HCV investigational vaccine has done testing in animal models.
Human Challenge Trial
“There is a collective consensus we need to speed up the clinical development of hepatitis c vaccines,” Houghton explained. As such, they have developed a plan to perform a human challenge trial assuming they are able to get through phase 1 trials. They are speaking with regulatory agencies around the world including Health Canada and the FDA and discussing the potential human challenge trial.
“If we show a vaccine candidate is safe in a phase 1 clinical trial, and it induces the kinds of responses we are looking for—cross neutralizing antibodies against most of the world’s strains, cellular immune responses to most of the strains—then what we would like to do to accelerate clinical development and delivery to the people that need this, we want to vaccinate volunteers and challenge them with the virus itself,” Houghton explained. “In the event those people become infected we can treat them with antivirals and cure them.”
Houghton is optimistic about the chances of their investigational vaccine getting approved. “I’m very encouraged that we can make a vaccine to the Hep C virus.”
In part one of a two-part interview with Contagion, Houghton discusses how they went about discovering the hepatitis C virus, the development of their vaccine, and the possibility of a human challenge trial and the potential timeline for it.
For those who are interested, the second part of the interview can be viewed here.