Know your vax

Thanks to 140 years of vaccine research, we’re now equipped with a range of weapons against a variety of viruses. Here’s how they work.

It’s a question that has concerned military generals across the ages – how do you prepare for an enemy that could attack at any moment? Solutions might include teaching soldiers what the enemy will look like, and then preparing suitable defences.

The same question has concerned doctors and health researchers as they develop methods to prepare the body to fight various viruses and bacteria. It would be laughable to think that armed forces today would wield the weapons of the sword and sandal days. Similarly, the developers of today’s vaccines have not only more tools in their armamentarium, but more precise and effective ones.

“It’s been an evolution of methodologies over 140 years and become so much more sophisticated,” says Professor Tony Cunningham, Co-Director of the Centre for Virus Research at Westmead Institute for Medical Research.

Cunningham has been involved in the development and release of a new shingles vaccine called Shingrix. Whereas the previous, longstanding shingles vaccine had about a 50% efficacy rate after 8 years, the new one has closer to 90% efficacy. It was only possible because of techniques developed over the past few decades.

Professor Kristine Macartney, Director of the National Centre for Immunisation Research and Surveillance, says today’s vaccine technologies are so much more advanced. 

“Now we are understanding so much more about the pathogen, and we can pull out what part of the pathogen might be the best to provoke an immune response and design the vaccine around that.”

Cunningham says there is still a lot more work to be done. “We have 50% – at best – efficacy with the flu vaccine. We’re trying to develop something that will be effective against all flu strains. And we still have no vaccine for HIV. So a lot of us are working on developing vaccines.”

During the COVID-19 pandemic, we have seen misinformation on social media and resulting confusion about vaccines. So it’s worth revisiting the different vaccine types and seeing how they work.

Every vaccine aims to create an immune response – to prepare the body’s immune system to recognise and fight the potential infiltrator. The various vaccine types basically find different ways to do this, or have different ways of smuggling the information into the immune system, past the body’s defences that try to keep foreign things out.

Attenuated virus: One of the first vaccine methods was grabbing the whole problem virus and weakening or ‘attenuating’ it, so it would cause an immune response without all the associated nasty symptoms. As large amounts of often slow-growing virus need to be cultivated for this, these vaccines can be expensive to produce, and can carry a higher risk for immune-compromised people. Yet the method is still widely used in some vaccines.

“We still use it in chickenpox vaccine in kids – it’s a very good one,” says Cunningham. “So is measles-mumps-rubella (MMR).”

Inactivated virus: Here, the virus is made inactive through chemical or heat treatment. Polio and hepatitis A vaccines employ this method. However, the Chinese-developed COVID vaccine, Sinovac, has only had a 50–60% efficacy rate using inactivated virus.

“Often you don’t get a high enough concentration of the particular protein you want,” Cunningham explains.

Protein: As with the new shingles vaccine, protein vaccines take individual proteins out of the virus and stick them onto an artificial surface to provoke the reaction in the immune system, or take parts of the virus and join them back together to form a new compound that looks a bit like the virus, but is missing most of the information.

“If you pick the right single protein, you get a much better immune response than when the system is distracted by other proteins,” Cunningham says. In the COVID vaccine Novavax, the distinctive COVID spike protein has been stuck all over a surface to resemble tiny COVID particles.

Viral vectors: In this method, genetic information (DNA or RNA) about the problem virus is inserted into another, harmless virus, which is then introduced to the body. The AstraZeneca COVID vaccine uses a form of a harmless virus first found in chimpanzees, and slots the ‘spike’ coding into it.

The trick with these vaccines is finding a carrier virus that isn’t currently well known to human immune systems. Otherwise the immune response might be directed against the carrier virus rather than the problem virus. Some viruses have a very small genome, which makes them easy to manipulate. The first major viral vector vaccines were used against the Ebola virus in 2014–2016 and had a huge impact in combating its spread.

mRNA: The technology for this new vaccine type has been developed over the past two decades. In it, tiny strands of mRNA are changed to deliver a message about the virus. In the case of Pfizer and Moderna COVID vaccines, the mRNA sends a message to make the spike protein, creating the same immune response as if the coronavirus spikes themselves were seen by the immune system. The trick with this technique has been finding ways to smuggle the fragile mRNA into the cell so it isn’t destroyed before releasing its information. In the COVID vaccines, the mRNA is packaged inside tiny fat globules which, once injected into the body, enter nearby cells and the lymphatic system. From there the cells produce the proteins that trigger an immune response to protect the body from the virus.

“RNA is the new kid on the block and has proved remarkably successful, which was a bit of a surprise to some as RNA is such a fragile molecule,” Cunningham says. RNA vaccines are very quick to produce, and therefore can be quickly adapted to take on new strains.

Toxoid: In this approach, rather than attacking the whole invading problem, the immune system is primed to target and inactivate the toxins that cause the symptoms. This successful technique is used in tetanus and diphtheria vaccines. “It means you’re really neutralising any negative effect,” says Professor Macartney. “It doesn’t necessarily mean you won’t have bacteria – you could still have diphtheria sticking to the back of your throat for a few days – but its toxin or poison is not going to make you sick.”

Cunningham says that, as accurate information about vaccines has increasingly been disseminated, and as we have witnessed the virulence of the COVID Delta strain, more and more people have become comfortable with some of the advanced vaccines. “I’m seeing a lot of people change their attitude very quickly,” he says. “I think the pendulum is swinging.”