The Covid-19 immunisation race

Farah Hancock reports on the Holy Grails, Hail Marys and hopes of magic blood in the race for immunisation against the virus that causes Covid-19

With much of the world locked down, the question is when will international mingling be safe without 14 quarantine days either side of a journey?

New Zealand is seeing results from lockdown, but as WHO director-general Dr Tedros Adhanom Ghebreyesus pointed out lockdowns are local and temporary "to take the heat out of a country’s epidemic”.

Hopes of ending the pandemic are pinned on a vaccine.

The race to create one is emerging as one of the most fascinating vaccine races in history. More than 100 vaccines are now in research and development with around six of these being used in clinical trials.

“It is incredible. I’ve never seen anything like it,” said University of Auckland’s Helen Petousis-Harris. She’s a vaccinologist and a co-leader of the Global Vaccine Data Network, a multinational consortium dedicated to collaboration in vaccine safety studies.

With the proviso vaccine-makers don't face hurdles, she’s picking September for the date when the first of the vaccines under way will be assessed for safety. All going well, there's a chance something could be available to be upscaled for production and distribution by the end of the year.

In the world of vaccine creation, this is an extraordinarily short time.

As well as unprecedented cooperation between some of the bigger players, smaller players using new technologies are participants in the race thanks to a shift of thinking in the way new diseases can be combated. 

“People have been saying for years, we are not going to be able to respond to emerging pathogens, we've got a problem.

“We need to revisit the traditional approaches to making vaccines, without completely relying on big pharma. With those very big, very slow wheels to turn it’s not going to serve us when we get a new flu.”

One of the factors in the new, nimble approach has been the formation of the Coalition for Epidemic Preparedness Innovation (CEPI). It’s a global partnership between public, private, philanthropic, and civil society organisations formed in 2017 which works to speed up the development of vaccines for new diseases. 

CEPI has been busy raising money - $750 million to date - and has funded eight different Covid-19 vaccine projects.

Some of these projects are using what’s considered new technology. 

Different technology, same virus

There’s a jargon soup of different types of vaccines being created for Covid-19. Live, inactivated, replicating or non-replicating viral vector, protein, virus-like particles, DNA and RNA. All of them hope to achieve the Holy Grail in vaccine creation tooling up a person’s body against an invader before they meet it for real. This is usually done by creating antibodies - pre-trained operatives - to battle the virus. 

Getting a vaccine is a bit like when James Bond gets a pre-mission briefing.

Vaccines can tell the body what a potential assailant looks like and supply nifty gadgets to thwart the assailant with, or in the case of RNA vaccines, give the body information to build its own tools on the fly.

It’s one of these new-fangled building-tools-on-the-fly RNA vaccines which could be among the first products to be assessed. Part of the attraction of this technique is speed of production. Once the genetic code of a virus is released, production can be done synthetically - there’s no need to grow a virus in cell cultures. 

So far, no vaccine made with this technology is approved for use in humans yet, although Petousis-Harris said a successful vaccine using the technique was made for a different Coronavirus, MERS.

“It went to human trials and the participants in the trials made the right sort of antibodies. They found it likely that it would offer protection against MERS,” said Petousis-Harris.

Part of what’s held back the clinical trials for some of these newer-style vaccines is cash. It’s hard to get funding if your vaccine isn’t essential to combat an immediate threat. 

“It’s not like the technology hasn’t existed, but you have to invest in it.”

Covid-19 is a game-changer. Moderna, a Cambridge, Massachusetts-based biotechnology company, is involved in one of the CEPI-funded projects. Its RNA vaccine is already in phase one clinical trials. 

The Hail Mary human challenge argument

There are typically three phases to testing a vaccine. 

Phase one tests a very small number of healthy people, the key questions are: is it safe, is it producing antibodies? Phase two tests a bigger group. During this phase, the dosage is tweaked to see what the optimal dose should be. Again, antibodies are measured to get an idea of whether the vaccine is triggering the immune system.

Phase three tests thousands of people representing a cross-section of a population. These people, split into a control group that gets a placebo and a group that gets the vaccine, are monitored for months to see if they catch the virus.

An ethically perplexing suggestion has been posed for Covid-19 vaccines. The long wait involved in phase three could be sped up by deliberately infecting healthy people rather than waiting to see if they get the virus.

It’s an approach used in the testing of the first-ever vaccine, for smallpox, where an eight-year-old boy, and later prisoners on death row were roped in as ‘volunteers’. Freedom was offered to the prisoners who survived infection. 

In modern times, this technique - where a milder illness, or version of an illness can be used - is still occasionally in use. Deliberately infecting people with a potentially fatal virus is considered unethical. 

A paper published in The Journal of Infectious Diseases suggests this approach. A human challenge would ask for volunteers to bypass the lengthy phase three. Only healthy young people would be selected and after infection they would receive a high level of medical care.

It’s a pandemic Hail Mary that has struck a chord. On just one website, more than 1000 people have registered their willingness to be deliberately infected in order to speed up a vaccine's release.

But does a final phase where participants don’t represent a cross-section of society provide a scientifically sound result? 

“You wouldn't make it [a vaccine] available based on just that, but it would give a huge, very quick advantage,” said Petousis-Harris.

Passive immunisation from magic blood

There’s yet another strand to prevention referred to as passive immunisation rather than a vaccine.

Blood from people who have recovered from Covid-19 contains a magic ingredient - antibodies. 

These can be extracted from the blood and given to other people to help prevent or lessen the impacts of the disease. 

The science behind this approach isn’t new and a Japanese company is collecting blood plasma in the hope of marketing a serum in a few months. There's even talk it's a technique New Zealand could adopt.  

This approach comes with challenges, not least of which is getting enough blood. Recovered people may need to have blood extracted regularly to meet needs.

If one recovered person could be bled enough to provide a treatment for 10 other people, 7.8 billion inhabitants would need 780 million people to have recovered from the virus. At present there are just over 784,000 recovered cases.

Petousis-Harris, who is involved in assessing the safety of vaccines, said her prediction of September as when work will begin is based on her conversations with vaccine developers and vaccine assessors. She's picking an RNA vaccine, and possibly a non-replicating viral vector vaccine developed by Oxford University as among the first cabs off the rank.

She stresses there are no promises, saying it's a Hail Mary of the "moon, the stars and the planets" aligning.  

“It's about everything going well and these things can fall over at any stage.”

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