by MERLIN CROSSLEY

Imagine there’s no COVID vaccine. It’s easy if you try.

Imagine if the world’s scientists just couldn’t do it. No one has yet made an effective vaccine against AIDS or malaria or the common cold.

When the COVID pandemic began many feared that it would also be impossible to make a vaccine against a coronavirus, like SARS-CoV-2. There were no vaccines against coronaviruses. They attack through the respiratory system and it wasn’t obvious that immune defences would block invasion. It also wasn’t guaranteed that the virus’s docking protein, the spike protein, could be held in the right configuration to generate a good immune response. Worse still when researchers had previously tried to make a vaccine against the first SARS virus, it turned out that it facilitated the uptake of the virus into cells and made the disease worse.

That hasn’t happened with SARS-CoV-2. Happily, most of the vaccines have shown great safety and efficacy. Nothing in this world is totally safe or totally effective but the vaccines are a real triumph.

The vaccines are working. Those commentators, who at the outset, said that COVID was just like the flu were demonstrably wrong. It spread faster and overwhelmed health systems. Now, however, the countries with high levels of vaccination show that perhaps it can be rendered a lot more like the flu. In Australia up to around ten people a day might die of the flu in any given year. The COVID mortality rates in countries with good vaccination programs are a bit like that.

No vaccines are 100 per cent effective, immunity may wane, new variants may arise, and consider this – after SARS-CoV-2 another completely new virus may emerge and spread across the world. And next time we may not be successful in generating such effective vaccines.

So, again, imagine there is no vaccine?

What would we do?

We would resort to broader knowledge strategies across a range of research areas.

In the case of HIV the initial answer was epidemiology. Understanding the mode of transmission was the first breakthrough. You can protect yourself from HIV by practicing safe sex and screening blood products. Identifying modes of transmission, as well as developing rapid diagnostic tests for viral genomes, on-site testing for actual virus, and antibody testing for past infection is enormously helpful.

The next step is often pharmacology. HIV replication requires a number of enzymes that humans don’t need. Most notably a reverse transcriptase that copies its RNA genome into DNA so that it can merge into the DNA in our white blood cells. The first drugs against HIV were tiny molecules that stuck to reverse transcriptase and blocked its action – like a spanner in the works. Later other inhibitors were developed, targeting HIV protein-cutting enzymes that humans don’t use. There are now a range of very effective drugs against HIV that limit disease and even transmission.

Researchers are already investigating drugs against SARS-CoV-2. Its genome is well-understood now and targets for inhibition are being prioritised. The first drugs, things that had been used against SARS and other related viruses, remdesivir and hydroxychloroquine, didn’t really work. But it is likely that new anti-virals will be developed.

Unfortunately, it takes a few years to develop an effective anti-viral drug and test that it’s safe. The drugs probably won’t cure COVID outright but I bet they’ll save lives.

Another option involves trying to artificially replicate what our body does to fight infection. Our B cells generate antibodies that bind to and neutralise the virus. Initial attempts to just harvest blood and purify antibodies from affected patients (so called convalescent plasma) weren’t effective. But researchers now have carefully identified what are known as monoclonal antibodies that directly target the spike protein and can be produced in large quantities in labs. These could be made widely available and may be very helpful.

There will also be other options but that’s enough to make the point. And the point is this. No single research solution is ever guaranteed. During the pandemic there was considerable urgency and funding was allocated quickly to clinical trials on hydroxychloroquine and other wild goose chases. And there was a well-justified rush for vaccines. There was no time to properly engage the peer review system. Now as we emerge from this pandemic, and we will soon I hope, it is important to recognise that a full ecosystem of high quality research is necessary.

Identifying a range of projects by peer review is the best way to maintain quality and a properly diversified portfolio of research investment.

We are fortunate the government approved $1bn to support Australian university research during the pandemic and the simple distribution mechanism broadly reflected the peer reviewed revenues of the various universities. The support should be extended for another year now that we know the crisis is dragging out. We are also lucky to have the Medical Research Future Fund. The trick will be to target the resources properly using peer review, so we provide the maximal protection, the protection that comes from running a high quality knowledge agenda.

Professor Merlin Crossley

Deputy Vice-Chancellor Academic and Student Life

UNSW SYDNEY