How this scientist played a key role in three Covid vaccines

By Indira Laisram
Prof S S Vasan

When a gentleman flew to Melbourne from Guandong on 19 January last year, he was not just the first confirmed case of the novel coronavirus in Australia, he was also the first imported case in the world. The Victorian Infectious Diseases Reference Laboratory (VIDRL) isolated the virus from his sample and shared it the next day with Prof S S Vasan at the Australian Centre for Disease Preparedness (ACDP) in Geelong, the world’s largest high-containment facility of its kind. For Vasan, who has previously worked on viral diseases such as Chikungunya, Dengue and Ebola, this would herald the busiest time in his career, leading the crucial preclinical evaluation of three key vaccine candidates—including the now licensed Oxford-AstraZeneca-Covishield vaccine that has reached the mark of 1 billion doses administered worldwide.

India-born Vasan and his project team grew and characterised the virus, creating sufficient working stocks to conduct pre-clinical research and vaccine evaluation. “We ended up being the first outside of China to grow stocks of the virus and determine its characteristics. The same VIDRL isolate called ‘VIC01’ also went to England and started the UK’s research as well,” he says.

In 2019, Vasan’s proposal to increase pandemic preparedness for a future ‘Disease-X’ was amongst those selected by the global body Coalition for Epidemic Preparedness Innovations (CEPI). So, when he approached CEPI in January 2020, they promptly agreed to fund his team at Australia’s science agency CSIRO, leading to two key breakthroughs within months. Vasan and his team showed that ferrets are susceptible and will be a suitable model to test COVID-19 vaccines, which led to CEPI funding them further to evaluate two of their lead candidates—Oxford’s established adenovirus technology and the novel DNA vaccine of US-based Inovio Pharmaceuticals.

“Normally before a vaccine enters human trials, you have to evaluate it in two different animal models. So, the Oxford vaccine was concurrently evaluated in monkeys at the US National Institutes of Health while we were working on ferrets—and these along with other data from the manufacturers went to different regulators to get the approvals for phased clinical studies in people,” says Vasan, adding, “My team’s work was pivotal.”

Prof Vasan at the World Heath Organisation, Geneva

The biggest campaign in world history is in progress to get people vaccinated, and of the four billion doses already administered, a quarter is Oxford’s vaccine. “It is the world’s workhorse vaccine that’s also been approved in Australia, India and the UK,” he observes.

As reported by science journal Nature on 5 April 2020, Vasan first proposed comparing its efficacy as nasal drops versus injection. “We showed that giving it intranasally is more protective in ferrets, leading to further trials in England and the USA,” he says with a smile.

So, if we get this vaccine or its booster as nasal drops in the future, the world has CSIRO to thank for this methodological improvement.

As COVID-19 Project Leader at the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Vasan was awarded the science agency’s Chairman’s Medal 2020, the highest award bestowed on his project team for critical preclinical evaluation of the Oxford and Inovio vaccines.

Inovio recently announced successful Phase 2 results, while Vasan and his team played a critical role in a third vaccine. Developed by the Indian Institute of Science and its Bengaluru-based spin-out company Mynvax, it’s a ‘warm vaccine’ which can withstand 37 degrees for a month and even 100 degrees up to 90 minutes. “My laboratory tested its efficacy against the Alpha, Beta, Gama and Delta variants of concern and it’s effective against all four,” he says.

These findings communicated in June 2021 helped the Institute raise the required funds they were desperately looking for their next phase of trials in humans. On 19 July, Mynvax announced it has managed to raise US$ 4.2 million, which raises hope for a vaccine that eliminates expensive cold chain.

The team at the Australian Centre for Disease Preparedness, Geelong, which is the world’s largest high-containment zone of its kind

With many vaccines in the fray, Vasan has refocused on affordable therapies which he says is the currently unmet need. His influence has grown; he has just secured AU$ 1.7 million research grant towards developing a faster way of screening existing drugs and advancing them for the treatment of COVID-19 and long COVID.

The grant, funded jointly by Australia’s Medical Research Future Fund and the CSIRO—has set him an ambitious one-year challenge to find and evaluate at least three repurposed drugs using stem cells, systems biology and machine learning approaches. “Vaccines are critical to our response but by themselves they cannot solve the pandemic; we urgently need safe, effective and affordable treatments that targets the virus, and a great place to look are existing drugs approved for other conditions,” he explains, as drugs like dexamethasone don’t actually target the virus.

“We are using stem cell-derived organoids, these are like miniature organs representing relevant parts of your body but outside of it, and we will be infecting them with the key virus variants to see if the chosen drugs can clear the infection. If they do, as they are already approved for some other purpose, they could be fast tracked for evaluation in people.”

The other important aspect in the research is looking at systems biology, which is an approach in biomedical research to understanding the larger picture. As this would generate ‘Big Data’, Vasan is working with his CSIRO bioinformatics colleague Dr Laurence Wilson and UNSW data science expert Dr Rohitash Chandra to use machine learning techniques to analyse it.

Vasan’s team was the first to show that ferrets are susceptible and a good model for COVID-19 vaccine evaluation

Interestingly, Vasan, Wilson and other colleagues were also one of the first in the world to publish a peer-reviewed paper early in 2020 on how the coronavirus would evolve. “Most of our predictions have come true, and we have developed a sophisticated way to keep up with the virus and its mutations of consequence. Australia, due to its small population, has a single national science agency, so we have leveraged that to work across disciplines. I have been collaborating with Dr Michael Kuiper in our high-performance computing division ‘Data61’, to model the virus and anticipate how future variants could emerge. Such insights will inform our response as this virus continues to evolve in the coming years, and as other viruses inevitably emerge,” he predicts.

“Our model routinely scans thousands of mutations across hundreds of countries so we can keep on top of the variants.” With one of the variants in mid-2020 called the ‘G strain’, Vasan and his team were the first to prove that its ‘D614G’ mutation will not affect vaccines. Recently, they were able to show that some first-generation vaccines are affected by variants particularly the Beta and the Delta, but that second-generation vaccines like the Mynvax neutralises all the variants well. These findings by Vasan’s team are peer reviewed and published now, contributing to a vast body of science.

Vasan completed Masters degrees in BITS Pilani and the Indian Institute of Science, both declared ‘Institutes of Eminence’ by the Indian government, before his doctorate at Oxford as an Indian Rhodes Scholar. He worked for the University’s spin-out company on arboviral diseases, and subsequently at the British high-containment facility in Porton Down, before joining the CSIRO in 2019. “It’s a coincidence that I played a role in evaluating the vaccines developed by two of my almae maters, but a happy one nevertheless,” he reflects.

While it is thrilling to work on these projects, he also says, “You are no different to World War II soldiers on the frontline.”

Vasan and his team have not had a proper break since December 2019, but did get some respite in late 2020 before the variants started to emerge. But it’s a coalition of the willing, he says. The projects are broken down into work packages with competent colleagues leading the specific packages and responsibilities.

Also, a mental health champion at CSIRO, he ensures people have an opportunity to talk about how they are feeling “and often that little thing where you stop to ask people if they want a cup of tea and if are they OK—that’s very important”.

Of course, the work has its own reward. But in the end, it all comes down to people working as a team to solve ‘wicked’ problems, quips Vasan. “If we don’t get that right and communicate well with each other, it is not possible to do good science.”

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