One of Australia’s leading COVID-19 vaccines has been scrapped – for a surprising reason
Maddie Massy-Westropp
December 27, 2020
A deal for the Australian government to purchase more than 50 million doses of a promising new COVID-19 vaccine, developed by the University of Queensland (UQ) and global biotechnology company CSL limited, has been abruptly terminated. In a statement to the Australian Stock Exchange on December 11, UQ and CSL announced that the vaccine would not progress to Phase 2/3 clinical trials.
A promising vaccine produced using cutting-edge technology
The UQ-CSL vaccine contains the Spike protein, a molecule located on the coronavirus surface. The Spike protein enables the virus to enter human and other animal host cells, where it replicates itself. When the vaccine is administered to a person, the immune system recognises the Spike protein and generates neutralising antibodies which can bind to it. If that person is exposed to COVID-19 in the future, those same antibodies can attack the Spike protein on the coronavirus surface, preventing the virus from entering host cells and replicating. The Spike protein was kept in a stable form in the vaccine using the novel, patented molecular clamp technology which UQ has been developing for the past 10 years.
Initial testing in animals of the UQ-CSL vaccine showed very promising results. When given the vaccine, hamsters produced high levels of neutralising antibody able to bind to the coronavirus Spike protein. According to Keith Chappell, the UQ project co-lead, the immune response was “better than the average level of antibodies found in patients who have recovered from COVID-19”. Following these exciting findings, the Australian government finalised a deal with CSL to supply 51 million doses of the vaccine, should human clinical trials be successful.
Unexpected results during clinical trials
Phase I clinical trials for the UQ-CSL vaccine started in July, to assess safety and production of neutralising antibodies in human volunteers. The researchers administered different doses of the vaccine to participants and measured various side effects, as well as levels of antibodies against the COVID-19 Spike protein.
What is a Phase I clinical trial?
Phase I trials aim to find the highest dose of a new drug humans can take, without severe side effects. Initially, very small doses of the drug are given to a few patients. Larger doses are given to other patients, with the dosage increasing until the desired therapeutic effect is seen or the side effects become too severe.
The treatment may help patients, but the main objective of Phase I trials is to test its safety. If the treatment is found to be safe enough, it can proceed to a Phase II clinical trial.
After receiving the vaccine, the trial participants experienced minimal side effects and produced high levels of COVID-19 antibodies. However, the participants also produced antibodies specific for glycoprotein 41 (gp41), a molecule found on the surface of Human Immunodeficiency Virus (HIV). This meant that the participants received positive results for some HIV tests, which look for the presence of gp41 antibodies. Follow-up testing confirmed that these were false-positive results, and the trial participants were not infected with HIV.
So where did the HIV antibodies come from?
On its own, the COVID-19 Spike protein is unstable, tending to lose its original shape and become unrecognisable to the immune system. The researchers used their molecular clamp technology to fuse the Spike protein together with two fragments of gp41. By itself, gp41 is harmless and does not cause HIV infection. Adding gp41 stabilised the Spike protein, ensuring that it kept its original shape and could elicit an immune response after the vaccine was administered.
However, the trial participants also had an immune response against the gp41 component of the vaccine. This has no health consequences at all, but widespread rollout of the vaccine could complicate the HIV screening process. Due to the production of gp41 antibodies, many people who have received the vaccine could falsely test positive on the standard HIV test. Other HIV diagnostic tests would have to be used.
Another issue relates to the stigma surrounding HIV, which could impact public perception of the UQ-CSL vaccine’s safety and lower its uptake. Community confidence in vaccine development is critical, with a new survey by The Australian National University showing that 41% of Australian adults would be hesitant about receiving a COVID-19 vaccine.
A tough decision was made
On December 11, UQ and CSL together announced that clinical trials for their COVID-19 vaccine have been abandoned. According to Paul Young, the other UQ project co-lead, the vaccine could be re-engineered to prevent the production of gp41 antibodies. However, this could introduce a delay of a year or more, and “the urgent need for a vaccine has to be everyone’s priority.” The Australian COVID-19 vaccination program is still scheduled to start early in 2021, with agreements for the supply of several other vaccines, including those developed by the University of Oxford/AstraZeneca, Novavax and Pfizer/BioNTech.
Whilst the decision not to proceed with the UQ-CSL vaccine was disappointing, there is a silver lining for the researchers at UQ. The molecular clamp technology successfully stabilised the COVID-19 Spike protein, leading to strong immune responses in trial participants, and did not cause any adverse health effects. With further work, this novel technology could prove invaluable to vaccine development in the future.