Covid-19 Response Minister Chris Hipkins announces that NZ has surpassed 300,000 vaccines delivered and set new daily records for dosage numbers. Video / Derek Cheng
Drew Weissman is not ready to rest on his laurels. He's already thinking about the next coronavirus variant – the one that will come after the Indian variant, or the Kent variant or the South African variant, and demolish the defences of our vaccines. Or rather, to give him his due, his vaccines.
"Moderna has already started a clinical trial with the South African variant," he says. "Pfizer is doing the same. My concern is, I don't think that's the right approach." Soon enough, he says, pharma companies will have to update again, and then again, in an eternal battle of cat and mouse.
Wouldn't it be better, he says, if Covid vaccines worked not by identifying what makes variants different but against what they have in common. He's doing just that. "We're making a vaccine that will protect against every variant that's ever been produced and should protect against all possible variants that appear in the future."
It's a bold claim. But Weissman isn't finished there. "We've had three coronavirus epidemics in 20 years [Sars, Mers and Covid]. It would be foolish to think we're not going to have more. So we've also been working on our pan-coronavirus vaccine."
Coming from anyone else, such claims of a universal shot against one of humanity's deadliest viral foes might sound fanciful. But Weissman, professor of medicine at the University of Pennsylvania, is notably reserved and softly spoken on our Zoom call. And perhaps most importantly, he has form to back his claims up, for in the past year his life's work has transformed human health.
Drew Weissman, professor of medicine at the University of Pennsylvania, had been working on vaccines for a decade before Covid struck. Photo / Pennsylvania University, via YouTube
"My wife and kids get mad at me because I don't show the enjoyment of the accomplishment," he says, stroking the ears of his immense white cat, Xander.
That accomplishment has been to develop not just a vaccine for Covid, but a whole new vaccine technology which, instead of priming our immune response by injecting us with bits of virus (like the AstraZeneca vaccine), uses a genetic courier called mRNA (messenger RNA) to teach our bodies how to build those bits themselves.
— The Drew Weissman Lab (@WeissmanLab) May 5, 2021
The technique, never deployed before the pandemic, has been astonishingly successful. Moderna and Pfizer vaccines, which both use it, have a 95 per cent effectiveness rate, compared with about 82 per cent for AstraZeneca.
More significant even than that, however, is the fact that like any courier, mRNA can be loaded with new parcels while maintaining the same delivery mechanism, meaning it can be updated to carry instructions to our cells that could vaccinate against malaria or herpes, or fight back and beat cancer and HIV.
From the ashes of the pandemic's destruction is rising the phoenix of a medical revolution. "It's a game changer," says Dr Zoltan Kis at Imperial College London's Future Vaccine Manufacturing Hub.
For a long time, however, it did not look like it was going to work at all. In the late 1990s Weissman, who was working on dendritic cells – "the cells that start all new immune reactions" – met Kati Kariko, who was working with RNA.
The pair decided to put their two subjects of interest together. They realised that, if it worked, their system would be able to deliver instructions so that the body could build specific proteins – to calm inflammation in stroke patients, say, or deliver a vital protein called CFTR to cystic fibrosis sufferers. "We knew when we first started it had enormous potential," says Weissman. There was just one problem. "It was unusable."
European Commission President Ursula von der Leyen, second left, speaks with Pfizer CEO Albert Bourla in Belgium. Photo / John Thys, Pool via AP, File
Every time he and Kariko tested it on mice, "the mouse got sick" with chronic inflammation. Its immune response was out of control. "We worked to solve that inflammation for seven years," he says. In 2005, they cracked it. "We could now deliver any therapeutic protein we wanted."
But the path is rarely straightforward when it comes to the multi-billion dollar business of developing new medicines. "We talked to pharmaceutical companies, biotech companies, venture capitalists, and they all basically said, 'Yeah, we've been burned by RNA before, and it's too hard to work with.' It took a lot of work to convince people."
Only after the founding in 2010 of the biotech company Moderna did Weissman and Kariko find a receptive audience. "Soon after that we spoke to BioNTech", where Kariko now works, and which eventually developed the Pfizer vaccine.
In the last decade, Weissman has been working on a variety of vaccines, with five in trials before Covid hit – including a universal flu vaccine, and two for HIV. But then, in early 2020, news of a novel virus began emerging from China. Its genetic code was posted online on January 10.
"We started working on Covid on January 12," says Weissman. Vaccine development had traditionally taken years. But on March 16, just two months later, Moderna put its Covid vaccine to clinical trial.
Speed of development is just one of mRNA's benefits ("plug in a new variant and in days you're ready to go", says Weissman). A second is manufacturing.
From the ashes of the pandemic’s destruction is rising the phoenix of a medical revolution. “It’s a game changer,” says Dr Zoltan Kis at Imperial College London’s Future Vaccine Manufacturing Hub.
In contrast to traditional vaccines, says Kis, "there are no living cells involved in the making of the RNA. It's synthetic. A biochemical process, simple, easy to purify it and to show quality, a much cleaner approach." Much less also goes much further. "Ten litres of RNA could make as many doses as 1000 litres of the conventional process."
Kis sees three stages to develop the potential of mRNA therapies. In the immediate term, they can be directed at infectious diseases like Covid, which Kis calls "the low-hanging fruit".
In the long term, they can be used to deliver gene-editing tools inside the body to fix inherited diseases like sickle cell. In the medium term, however, Kis sees the advent of personalised cancer vaccines.
Weissman explains how they would work: "You take out a piece of lung tumour or breast cancer or colon cancer or melanoma and sequence it" to reveal its genetic code. Such codes in cancer have many mutations, and a vaccine is based on those specific mutations, prompting the immune system to attack the cancer cells while leaving the body's cells unharmed.
This combination of MRI images provided by the University of Alabama in April 2021 shows scans of brain tumor, before and after a treatment that involves using viruses. Photo / UAB via AP
The technique has been shown to work well in melanoma, and less so in other cancers. But BioNTech already has one cancer vaccine in a phase two (of three) trial "looking at a whole bunch of different cancers".
As with many cutting edge techniques, the cost of such a vaccine would currently be prohibitive – "probably hundreds of thousands of dollars" says Weissman. But as the plunging price of gene sequencing has shown, costs can tumble dramatically as breakthrough technology becomes widely adopted.
It is in genetic medicine that Weissman hopes to make the biggest breakthrough, by loading up his RNA courier with a gene-editing tool called Crispr. The problem is hitting the right target in the body – typically the particles end up in the dendritic cells or being flushed out to the liver.
mRNA vaccine pioneer Drew Weissman received the Pfizer Covid-19 vaccine in December. Photo / Penn Medicine, File
But Weissman says that, as with the mouse inflammation of old, he has now overcome this big hurdle. "We've addressed that over the past couple of years. We can now target bone marrow stem cells," – a path to curing sickle cell – "we can target T-cells… for HIV cure."
Weissman cannot prevent a trickle of excitement permeating his self-contained manner as he describes such possibilities. "There is huge potential," he says. "Not everything is going to work. But some of it will. And we and others are going to keep developing this to get as many things to work to treat these diseases."
He is fully aware that, without the Covid pandemic, his work and its spin-offs would not be receiving the money and attention it now is. "Covid has certainly catapulted RNA into everybody's language and changed vaccine development," he says. It is a clearly a strange feeling being such a profound beneficiary of an event which has caused such disaster for so many.
It could have been very different. Like many researchers, having faced so many difficulties over so many years, he was primed for another disappointment when the effectiveness of mRNA vaccines was finally revealed last year.
"In animal trials of maybe 30 other vaccines – for everything from HIV, malaria, TB to influenza – we'd always get 100 per cent. But I'll be honest. I was really nervous that the efficacy for this might be 50 per cent or 70 per cent and I wouldn't have an explanation."
Then the data came out: 95 per cent effective. "I was so relieved. Back in the beginning we'd seen the potential as enormous. And it was finally coming true."
