Mon. Nov 28th, 2022


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Tomorrow’s vaccine: how Kiwis will take part in a medical revolution

6 min read

The Covid-19 crisis is ushering in a revolution in medical technology – and one that Kiwis are soon likely to benefit from first-hand.

That’s the advent of a new generation of vaccine which, after the coronavirus, could be thrown against everything from HIV to cancer.

It’s called an mRNA vaccine.

One candidate, which New Zealand has just locked in with a prepurchase agreement, is shaping up to be one of the first used widely in humans.

Scientists say the new tech has arrived at just the right time, bringing the global push for vaccines a solution that’s cheaper and faster to make, with a flexible, readily adaptable “plug and play” platform.

So how does it work – and how does it differ from what we already have?

The flu shots we typically get each year are “inactivated” vaccines – or those which don’t contain any live viruses.

Instead, a virus that has been rendered inactive by special treatment is introduced into the body, allowing the immune system to learn from its antigens how to fight live versions of it in the future.

Other common types of viral vaccines are protein or subunit vaccines, where only a fragment of the virus is used, and the “live attenuated” vaccines we use for chickenpox and measles, mumps and rubella.

In this case, the virus within the vaccine is still active – but has been weakened so that it can be replicated in the body just enough to trigger an immune response, without causing the disease it’s meant to guard against.

The mRNA vaccine, meanwhile, is part of a group called “nucleic acid vaccines” – or those which carry the genetic instructions to make the proteins that have been derived from the organism that causes the disease.

Over the past decade, scientists have been exploring the idea of making vaccines using the very DNA, or genetic code, that encodes the microbial proteins within pathogens.

But trials have generally failed to produce the immune response they were after.

This has led them to instead focus on mRNA – or messenger ribonucleic acid.

A smarter vaccine

All cells, and many viruses, use DNA as a kind of master set of instructions.

To carry them out, they’re translated into a simpler molecule – RNA.

Some viruses only contain RNA, and one of them is the coronavirus SARS-CoV-2, which causes Covid-19.

In extracting viral RNA and running it through genomic sequencing, for instance, scientists have been able to untangle different strains that have arrived in New Zealand, and trace the sources of outbreaks.

For vaccine makers, mRNA has proved an attractive option because, unlike DNA – which has to be somehow inserted into a cell’s inner-most part, or its nucleus, for the vaccine to work – RNA can be translated into protein as soon as it reaches the thick solution each cell is filled with, called cytoplasm.

Perhaps the most beautiful part of these vaccines is how the mRNA is transported to the cells in the first place.

Scientists have pioneered lipid nanoparticles, which form tiny droplets that protect the RNA molecules as they’re shuttled to their destinations.

What happens once they arrive?

RNA vaccines typically introduce an mRNA sequence – or the specific molecule that instructs our cells what to build – which is precoded for an antigen specific to a disease.

In the case of SARS-CoV-2, this was the “spike protein” the virus used to attach itself to cells – and played a big part in how quickly it spread within us, and to other people.

Packed in Pfizer and BioNTech’s BNT162 vaccine was the genetic material needed to grow the spike protein.

Once our cells produced and displayed this protein, it attracted and activated T cells – the roving hunters and killers of our immune system – and other immune cells.

The reason our body recognised the protein as something to get rid of was because our bodies recognise the SARS-CoV-2 spike protein as foreign.

In addition, viral genetic material contained special features that animals have evolved to recognise as dangerous, helping draw attention or enhance to the immune response.

Ultimately, the process generated an immune response that the body remembered if it ever came into contact with the actual virus – and made us into our own vaccine factories.

'Kicked into orbit'

University of Auckland vaccinologist Helen Petousis-Harris, an associate professor, said there were currently no RNA vaccines approved for human use, although several had been through clinical studies.

The pandemic had fast-tracked their development.

“These technologies have been in development for a few years, but they’ve lacked investment,” she said.

“Covid-19 has kind of picked up the ball and kicked it into orbit. But what really helped this tech along was enabling the fragile RNA molecule to be encapsulated in a nanoparticle case that protects it. That was a game-changer.”

Last month, the Government announced it had completed a deal with Pfizer and BioNTech that could see its vaccine rolled out here as early as next year – provided it met our regulations and successfully completed trial.

Progress has been promising.

As at last month, BNT162b2 was in the third and final Phase III trial at more than 120 sites around the world, with 28,000 people already having been given a second dose.

Pfizer and BioNTech have also launched a rolling submission to the European Medicines Agency, while Health Canada has begun a real-time review of its candidate.

And this week, the other mRNA candidate at phase 3 – Moderna’s mRNA-1273 – began a rolling review by Britain’s Medicines and Healthcare products Regulatory Agency.

The United States company has just completed enrolment of late-stage testing with 30,000 participants, with more than 25,000 people already having received a dose.

Being synthetic, the vaccines were ideal for scaling up – and came with a platform that could be quickly tweaked to target other infectious diseases. There is no need to grow the virus.

“They’re relatively cheap and easy to manufacture, compared to traditional vaccines – and trials so far tell us that they do appear to push all of the right buttons in the immune system to get a great response.”

What are the downsides?

Along with being licensed, and with a proven track record in humans, traditional vaccines are more easily stored than mRNA vaccines.

While current vaccines are typically kept at between 2C and 8C during storage and transport – called the “cold chain” – some mRNA vaccines need temperatures as low as -70C – posing logistical headaches.

“That’s something I understand can be overcome in time – but obviously it’s going to pose a real problem for low- or even middle-income countries.

“The early mRNA vaccines are also likely to be reactogenic. That means, at the injection site you might get a sore arm, or maybe you might get those fairly common vaccine responses, like fever or headache over the few hours afterward,” Petousis-Harris said.

“So while there’s no particular concern about serious events, they’re likely to be at the more reactogenic end of the spectrum, this indicates the body is generating an immune response.”

Researchers have already eyed up RNA vaccines for use in melanoma.

Some studies using mouse models have indicated a strong immune response that slowed tumour growth and improved survival rates in the mice.

There’s also potential to develop RNA vaccines for other cancers, along with notorious infectious diseases such as HIV, malaria and Ebola.

And what about uneasiness about genetic engineering?

Contrary to false claims widely shared on social media, mRNA vaccines didn’t genetically modify humans – nor did they create any genetically modified organism. This is because they do not have access to the human genome which is tucked away in the cells’ nucleus.

“And really, we’re not talking about something that can escape and cause mutant vegetables,” she said.

“Any potential biosecurity issues aresomething that our regulators will be working through.”

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