As of this week, a phase one clinical trial to test a potential new Ebola vaccine developed by researchers at the University of Wisconsin-Madison is underway in Japan.
Fifteen healthy young men* will receive two doses of the experimental vaccine. If the first group tolerates the vaccine, an additional group of up to 20 volunteers will receive a higher dose of the vaccine.
"In phase one, the main goal is safety," says Yoshihiro Kawaoka, professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine, who, with Peter Halfmann, a research associate professor in his lab, created the new vaccine.
The researchers will also measure whether the immune systems of the trial participants begin to mount protective responses by developing antibodies and an immune memory for the virus after receiving the vaccine. The phase one trial will not involve exposing subjects to Ebola virus.
Unlike other experimental vaccines, the vaccine created by Kawaoka and Halfmann does not rely on a secondary, live-though-weakened virus to deliver a portion of the Ebola virus to the human immune system. In fact, the new experimental vaccine is made from the whole Ebola virus, save for one gene that renders the virus in the vaccine noninfectious.
"Our vaccine contains everything except one small protein," says Kawaoka, also a professor of virology at the University of Tokyo. "It has more antigens to elicit protection and it’s an inactivated virus, so it’s safer."
Since more of the virus proteins are present in this vaccine relative to others, it also improves the chances the immune system develops a robust capacity to fight Ebola virus if a person is exposed.
The form of Ebola virus contained in the vaccine is a technology Halfmann created more than a decade ago, called DeltaVP30. The technology renders the virus incapable of reproducing itself because it eliminates a gene that makes a protein critical for this task. The virus can only grow in a special cellular system containing the missing protein, which is not found in human or animal cells. Prior to use in humans, it was proven safe and effective in mice, guinea pigs, and in non-human primates.
"Pete did all the groundwork to get to this point," Kawaoka says.
When he developed it, Halfmann never envisioned using the technology to produce an Ebola vaccine.
"It was basically just a research tool for me," he says. "I never really thought we would have the backing behind us to actually go for a vaccine... it’s exciting to see we’ve gone this far."
However, following a devastating Ebola outbreak in Western Africa between 2013 and 2016 that killed more than 11,000 people, Kawaoka was granted funding in early 2018 by the Japanese government to produce the number of doses needed to launch a phase one clinical trial.
He then approached Waisman Biomanufacturing at the UW-Madison Waisman Center to produce clinical-grade vaccine. The facility was able to provide expertise in manufacturing processes, quality control, product development and more.
"It’s very exciting to see this trial starting so quickly and we hope it’s successful," says Carl Ross, managing director of Waisman Biomanufacturing.
Kawaoka and Halfmann have also relied on much support from research team members in Japan, including Tokiko Watanabe, who is ensuring the clinical trial adheres to vaccine regulations and is facilitating communications between Halfmann and the group administering the vaccine; Hiroshi Yotsuyanagi, who is leading the clinical trial; and Fumitaka Nagamura, who is coordinating the trial.
Since August 2018, another Ebola outbreak has erupted in the Democratic Republic of Congo. More than 2,000 people have died. The need for a way to combat Ebola is acute.
However, arriving at a final, approved vaccine is neither quick nor inexpensive without additional funding and support, Kawaoka says.
"Hopefully this vaccine is safe in humans and leads to reasonably good immune responses," Kawaoka says. "After that, we need a company to take it to phases 2 and 3. That will involve hundreds of people and costs are going to go much higher."
*The current phase one clinical trial does not involve women in order to avoid subjects who may be pregnant.