Nine months after the SARS-CoV-2 virus first struck, 38 vaccine candidates are in clinical trials around the world. While some of the frontrunners are in the final stages of testing, two novel vaccine candidates are not far behind. Both use a self-replicating design to elicit a stronger immune response. One of the two, LUNAR-COV19 — a collaboration between Duke-NUS and California-based Arcturus Therapeutics, has entered phase II trials in Singapore.
In the race to be the first to develop a vaccine, many frontrunners relied on existing technologies to form the backbone of their COVID-19 vaccines. This allowed them to speed up their development.
Instead of relying on existing technologies, Duke-NUS saw a unique opportunity in partnering with Arcturus to develop a novel self-replicating messenger RNA (mRNA) vaccine. The Emerging Infectious Diseases Programme team believed that such a design could be a game-changer, delivering long-lasting immunity in a single jab.
As this was the first time that a self-replicating mRNA vaccine was being developed and the technology had not been tested in humans before, detailed pre-clinical studies were necessary before the vaccine was safe for human trials.
Here, the experience that Professor Ooi Eng Eong from Duke-NUS’ Emerging Infectious Diseases Programme had gained studying another virus proved invaluable.
Following the science to vaccines
Before the COVID-19 pandemic, Ooi, a dengue researcher at heart, focused on understanding why a second dengue infection often led to more severe disease. While he produced elegant findings in the lab, reviewers of his work would challenge whether this held true in humans.
That was when Ooi first approached Associate Professor Jenny Low, a senior consultant with the Department of Infectious Diseases at Singapore General Hospital.
“I said to Jenny, ‘Let’s settle this once and for all.’ But how do you do it safely? We couldn’t purposefully infect people with dengue, so we used vaccines,” said Ooi.
They turned to other flavivirus vaccines like the yellow fever vaccine. They proved the hypothesis that antibodies can enhance a related-virus infection. In the process, they also acquired a detailed data set about the body’s response to vaccines.
“Studying how humans respond to the yellow fever vaccine, we found out the causes of common vaccine side effects and the genes that need to be switched on/off to produce immune responses that give durable protection. And that’s what we want [from a vaccine],” said Ooi.
Crossing over to COVID-19
When the pandemic struck, Ooi used this knowledge to work with Arcturus to screen for the most promising vaccine candidate.
“With a solid scientific foundation, we knew what milestones to look out for,” he said. Milestones that would give the team the confidence that they were on the right track.
A thorough understanding of the pre-clinical workflow allowed Ooi and his team to run many steps concurrently. At the same time, Low worked on the necessary protocols that would underpin the first clinical trial.
“It is an impressive feat because this is our first time developing a vaccine, and within a span of four months, we’ve progressed from pre-clinical to clinical trials!” said Ooi.
And it seems to be paying off. While the official results are pending, Low, who leads the clinical trials, said that she and her team “are very optimistic that we are looking at an extremely promising vaccine”. In their phase II study, the team is looking to recruit more than 100 healthy subjects. Each participant will receive two doses of the vaccine one month apart.
If all goes well, Low hopes to start phase III before the end of the year. Interest from the public in supporting the trials has also been heartening, according to Low.
“It shows that people want to contribute to the betterment of science and medicine,” she added.
For Ooi, seeing what they have learnt and written about play out in real life has been satisfying: “It is no longer something we have just written about, but that we are now applying, and that’s cool.”