PERTH, Australia – The University of Queensland (UQ) and CSL Ltd. are abandoning their trials of an Australian COVID-19 vaccine after recipients generated HIV antibodies during phase I trials.
The response means the antibodies produced by the vaccine can interfere with HIV diagnostic tests. However, there was no possibility the vaccine caused infection, and routine follow-up tests confirmed no HIV virus was present, the partners said.
The University of Queensland began the phase I trial of the COVID-19 vaccine candidate – UQ-CSL v451 – in July to assess safety and immunogenicity in healthy volunteers. CSL was working toward taking responsibility for the phase II/III trial and large-scale manufacture of the vaccine if trials were successful.
The “molecular clamp” technology provides stability to the viral proteins that are the primary target of the immune defense system. The technology was designed as a platform approach to generate vaccines against a range of human and animal viruses.
As part of the vaccine’s design, the university’s researchers included a small fragment of a protein taken from the HIV virus, known as glycoprotein 41 (gp41). This has been used to create a “molecular clamp” to hold the vaccine’s synthetic virus in place, said Health Minister Greg Hunt.
“Although the university’s researchers have confirmed the protein fragment poses absolutely no health risk to people who have taken the vaccine, they have identified a partial antibody response to it among trial participants,” Hunt said. “This has the potential to interfere with some HIV screening tests that look for these antibodies, leading to a false positive test result.
“It is this impact on HIV screening – and in the context of other promising vaccine candidates becoming available – that has led to the government’s decision not to advance the vaccine,” Hunt said.
“Trial participants were fully informed of the possibility of a partial immune response to this component, but it was unexpected that the levels induced would interfere with certain HIV tests,” CSL said.
Vaccine was safe and effective but …
CSL stressed that the phase I trial showed that the UQ-CSL v451 vaccine elicits a robust response towards the virus and has a strong safety profile. There were no serious adverse events or safety concerns reported in the 216 trial participants. However, following consultation with the Australian Government, the decision was made not to progress the vaccine.
The vaccine was “producing very good antibodies,” and was likely to be effective in phase III trials, but the concern was public confidence, said Department of Health Secretary Brendan Murphy in a Dec. 11 press conference.
“And given that we have other successful candidate vaccines, this was a very difficult decision that CSL and we made together. But it was important to keep that public confidence. But I emphasize it was excellent research, it was a good platform, and it was likely to be an effective vaccine at preventing coronavirus, we think.”
UQ vaccine co-lead Paul Young said that although it was possible to re-engineer the vaccine, the team did not have the luxury of time needed.
“I said at the start of vaccine development that there were no guarantees, but what is really encouraging is that the core technology approach we used has passed the major clinical test. It is a safe and well-tolerated vaccine, producing the strong virus-neutralizing effect that we were hoping to see.
“We will continue to push forward and we are confident that with further work the Molecular Clamp technology will be a robust platform for future vaccine development here in Australia and to meet future biosecurity needs,” Young said.
The University of Queensland plans to submit the full data for peer review publication.
“While the discontinuation of UQ-CSL v451 is disappointing for Australia, as 51 million doses were to be supplied from this vaccine to the Commonwealth, for CSL the impact is likely to be negligible as we never viewed this agreement to be a windfall, but more likely to be based on payments received on a cost recovery basis (despite the financial consideration of this agreement were never disclosed),” wrote Morgans Health analyst Scott Power in a same-day research note.
A potential to confuse tests for HIV
“This story will be seen as a failure by many, but it is a live demonstration of how science works at its best. The quality of the science has not been diminished, but the willingness to accept the data and interpret accurately, and the integrity in reporting show the team to be our very best,” said David Tscharke, head of Immunology and Infectious Diseases at John Curtin School of Medical Research at the Australian National University in Canberra.
“This also demonstrates the rigor with which COVID-19 vaccine development is being pursued by all, from academic scientists, to pharmaceutical companies and the Australian Government. It lays to rest any claims of corners being cut in vaccine development.
“The result does not mean that this candidate vaccine is unsafe or might not be protective, it means there is the unfortunate potential to confuse tests for HIV in some people,” Tscharke said.
CSL Chief Scientific Officer Andrew Nash concurred with that, saying the outcome “highlights the risk of failure associated with early vaccine development, and the rigorous assessment involved in making decisions as to what discoveries advance.”
Prime Minister Scott Morrison said that Australia’s vaccine strategy was to choose several promising candidates, and the CSL/UQ vaccine was one of four that the country made advance purchase agreements for to ensure that the entire population would be covered.
“At no stage, can I assure you, that we believed that all four of those vaccines would likely get through that process. If that had occurred, that would have been truly extraordinary, based on the process of vaccine development not only in this country, but anywhere else. So that's why we spread our risk. That's why we backed important projects. And that's why we pre-prepared to ensure that we could deal with any issues along the way.”
Health Minister Hunt said that Australia remains on track for first vaccinations in March, and the entire population should be vaccinated in 2021.
To that end, CSL will manufacture 30 million doses of the Oxford/Astrazeneca plc vaccine candidate, with first doses planned for release to Australia early next year. In addition, CSL has agreed at the request of the Australian Government to manufacture an additional 20 million doses.
A further 11 million doses of the Novavax AG vaccine will be purchased, bringing the total for this vaccine to 51 million.
A purchasing agreement is also in place for the Pfizer Inc./BionTech SE COVID-19 vaccine, with 10 million doses scheduled for early 2021.
Meanwhile, CSL Behring Australia, a subsidiary of CSL Ltd., said it was still developing an anti-SARS-CoV-2 plasma product to treat people with serious complications of COVID-19 in Australia.
The product is being developed using donations of plasma from people who have recovered from COVID-19, as those donors have a high level of antibodies in their plasma. The antibodies are pooled, purified and concentrated to make COVID Immunoglobulin.
CSL Behring is part of the CoVIg-19 Plasma Alliance, an industry partnership to develop plasma-derived therapies for treating patients with serious complications of COVID-19.