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For a possible COVID-19 vaccine, the spike protein (structural model in the photo) of the pandemic coronavirus was stabilized with a bit of an HIV protein (red).
PR Young, Microbiology Australia (2020) 41: 109-112 CC BY
By Dennis Normile
SciencesThe COVID-19 report is supported by the Pulitzer Center and the Heising-Simons Foundation.
Sponsors of Australia’s homegrown COVID-19 candidate vaccine today announced the suspension of further development, after some of the first people to receive the vaccine in a safety trial raised antibodies against an unwanted target, the virus. AIDS. A small fragment of an HIV protein is a component of the vaccine that is used to add stability to the target of the desired antibody, the spike protein of the pandemic SARS-CoV-2 coronavirus.
Although the added component did not represent an actual HIV infection, the vaccine developers and the Australian government concluded that a widespread release of the candidate would interfere with HIV diagnostic testing and decided not to proceed with larger clinical trials that would have measured its protection against COVID-19. Given the high efficacy shown by several recent COVID-19 vaccines, other candidates still in development now likely have a higher bar to overcome in moving forward.
Related
the “molecular clamp“ The technology behind the Australian vaccine was developed by researchers at the University of Queensland (UQ) with the support of the global non-profit Coalition for Outbreak Preparedness Innovations (CEPI), which has supported multiple COVID candidate vaccines. -19. CSL Limited, to Melbourne, Australia–UQ-based pharmaceutical company that licensed the UQ candidate, was planning to take it through phase II and III trials and manufacture it.
Among the current COVID-19 candidate vaccines, “the molecular clamp is a unique approach,“ says Adam Taylor, a virologist at Griffith University, Gold Coast, who was not affiliated with the vaccine development effort. He explains that like many COVID-19 vaccines, including those that seem to have clear efficacy, the UQ-CSL candidate spikes SARS-CoV-2 for the human body to generate antibodies against the protein.
Spike plays a central role in infecting cells, folding and reconfiguring as it goes through the process of binding (or fusing) to a receptor protein in a human cell. The molecular clamp approach focuses on a prefusion configuration, which exposes hidden parts of the peak in its post-fusion form and can generate a more robust antibody response. But this conformation of the spike protein is unstable, so the Australian team introduced a bit of molecular material, the molecular clamp, to hold it in place. The UQ team found that a small 80 amino acid fragment of an HIV protein provided this stability. (Other groups have introduced mutations in the beak gene to create a more stable form.)
Unfortunately, that piece of HIV also generated antibodies that could confuse diagnostic tests. The researchers recognized the possibility that the HIV component could elicit an immune response. But, “MEIt was unexpected that the induced levels interfered with certain HIV tests,“ read a joint statement announcing the hiatus of candidate development that was posted online by UQ and CSL.
Aside from the problematic immune response of the HIV protein, the vaccine, administered to 216 participants in July, “elicits a robust response to the virus. [SARS-CoV-2] and has a strong safety profile,“ according to the statement. Phase I safety testing will continue to see how long antibodies to the HIV protein persist, although there are signs that the levels are already dropping. The university plans to submit the full data for peer-reviewed publication.
While it might be possible to redesign the vaccine, doing so would delay development by about a year, Paul Young, a UQ virologist who co-leads the vaccine team, said in the joint statement. He described the results of phase I as “really encouraging“ and said that “with more work, molecular clamp technology will be a solid platform for vaccine development in the future.“ In a statement, CEPI announced that it still believes that the concepts underlying the vaccine technology “are very promising.“ and will continue to support work at UQ on the molecular clamp platform.
Australian media reported that the government had signed an agreement to purchase 51 million doses of the UQ-CSL vaccine, but that it also has supply agreements for three other potential or tested COVID-19 vaccines. “Providing vaccines in the absence of UQ vaccine should not be a problem, assuming some [the others] are successful in their Phase 3 trials,“ Sanjaya Senanayake, an infectious disease specialist at the Australian National University, said in a statement distributed by the Australian Center for Science Media.
