key: cord-0044334-4lruc5or
authors: Young, Paul R
title: Disease X ver1.0: COVID-19
date: 2020-05-27
journal: Microbiol Aust
DOI: 10.1071/ma20028
sha: e3a17c1e3c0777ffd1dac100d34fc99745cd1421
doc_id: 44334
cord_uid: 4lruc5or

The SARS-Cov2 has presented the world with a novel pandemic challenge requiring a rapid response. This article provides a May 2020 snapshot from Professor Paul Young, who is part of a group working with urgency on Australia’s leading COVID-19 candidate vaccine.

pipeline to address the threat of emerging viral pathogens. The project was built around a patented platform technology that we had been developing here at the University of Queensland (UQ) for nearly 10 years 1 . We had already generated candidate subunit vaccines for 10 different viruses from a wide range of viral families and so were well placed to apply all that accumulated knowledge to this newly emerging virus. Initially, we viewed the task as an exercise to test the platform, not expecting the global spread that would follow. In those early days of January, we eagerly awaited the release of any viral sequence information. On 10 January 2020 the first full genome sequence of this new virus, a coronavirus like its predecessors SARS and MERS, was made public and overnight we had designed our first constructs.

We named our patented platform technology the Molecular The problem was that his approach resulted in a protein that was not that stable.

When he returned to my lab it was to work in a relatively new area for us, virus-bacterial interactions, but he asked if he could also continue to work on the RSV F story. I had been involved with Biota for a number of years in the late 1990s, expressing RSV F as a target for antiviral drug design, and through that work we had proposal and asked us to submit to the next call, which was to support platform technologies that could be applied to multiple pathogen targets. The call had a number of key criteria that needed to be met, the most notable being a 16-week timeline from pathogen discovery to delivery of sufficient vaccine to enter a Phase 1 clinical trial. A challenging ask, but one we felt we could meet, given the seven years of development we had already put into our MC approach. Our application brought together colleagues from the ANU, the Doherty Institute, University of Hong Kong and CSIRO teams at both the protein manufacturing facility at Clayton in Melbourne and the AAHL facility in Geelong. To prove the technology, we needed to generate three separate vaccines, two for 'demonstrator' targets, i.e. ones for which existing vaccines or technology was already available to compare, and one emerging pathogen. We chose influenza and RSV for our first two targets and, fortuitously as it would turn out, the coronavirus MERS for the emerging pathogen. We also suggested in our grant proposal that in our last year of the three year grant we should be subjected to a stress test. We would be supplied with an unknown viral sequence, from which we needed to design, develop, test and manufacture enough vaccine to enter a Phase 1 clinical trial.

That was meant to happen in 2021, but we received that first, very real 'stress test' sequence on 10 January this year. The first constructs were designed within the first 24 hours. On 21 January we received a formal request from CEPI to begin full development and manufacture of a vaccine candidate. Within three weeks of receiving the initial SARS-CoV-2 sequence we had chosen a lead construct. We went on to design, express and test more than 200 different constructs by the end of the 4th week, but we ended up moving forward with that first excellent lead candidate. A model of the clamped, trimeric pre-fusion SARS-CoV-2 Spike protein that we have generated as our vaccine candidate is shown in Figure 1a . Figure 1b While mice are obviously not humans, the levels of neutralising antibody induced was substantially higher than that seen in recovered COVID-19 patients and so we are hopeful that we may be able to induce even higher levels of antibody with our vaccine than that induced by natural infectionit is early days, but the data are promising. We have been substantially assisted by large pharma (GSK, CSL and Dynavax) reaching out to us to offer their tried and tested adjuvants for this work. We have also now entered our vaccine into toxicology and animal protection studies, both of which should reach data points by June that will allow us to enter our Phase 1 study on schedule.

With the global race on, and more than 100 vaccines in development, we have also encountered challenges such as limited Australia-based capacity to support critical, high-level containment, animal challenge studies. CSIRO's AAHL facility had moved quickly to begin ferret protection studies on vaccine candidates from two international groups (Oxford University and Inovio) and so was not available for our work. However, we were able to reach out to Viroclinics Xplore in The Netherlands and at the same time, expand the number of species we could test, as well as the overall scope of the studies.

Like everyone else, we have had to adjust to COVID-19 reaching our shores. By mid-March, the university was starting to shut down as many began working from home and practicing physical distancing (I still prefer that terminology to social distancing). We obviously needed to remain at work and in the lab and so, on 20

March we met for the last time as a single group, with appropriate distancing, and split into two teams that would no longer physically interact. That way, if one person fell ill we would not lose the whole group to home isolation. It has been a strange time at the university, to be in the middle of semester with all teaching now online and virtually no one on campus.

The timeline for development of a vaccine for COVID-19 has been a topic of much debate. The typical timeline for vaccine development, from conception to licensure is anything from 10-20 years, with five years being the most impressive to date.

Regardless, most commentators have been suggesting a 12-18 month timeline. This is a challenging ask, as there can be no corner cutting when it comes to safety and efficacy. The development of our vaccine is now the primary focus of the team and is continuing at pace, with all members of our consortium managing a range of variables that we continually need to adjust. What would normally take years to develop and Figure 2 . Schematic of the UQ COVID-19 subunit vaccine development pipeline. Funding stimulus has allowed us to advance and accelerate vaccine manufacture, cutting some 6 months off the expected vaccine delivery timeline.

finesse, we have only weeks and months to progress. But groups all over the world, developing the more than 100 candidate vaccines that are currently in play, will be having similar issues.

The major triage point is coming soon: the shift to large-scale manufacture. There is limited global capacity available and it is likely that only 3-4 vaccines will make their way through this transition point. We are hopeful that ours will be one of those vaccines that makes it through the months ahead, with its use ultimately contributing to the control of this once-in-a-lifetime pandemic.

The author declares no conflicts of interest.

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