How cancer research could help in the battle against COVID-19

Professor Stuart Berzins details the latest developments in the search for COVID-19 vaccines and treatments in this Q&A.

UPDATED

You research the immune system and how it regulates cancer. Can any of your research overlap or translate to current COVID-19 research?
Yes. Immunology is an important factor in most health areas and what we learn about the immune system in one area quite often has implications in other areas. My group has been investigating how immune responses against cancer are regulated and we have identified a subset of specialised immune T cells that appear to be important in this area. This is very interesting in the context of COVID research because there seem to be strong correlations between the severity of COVID symptoms and changes in the characteristics of these cells. This means that what we have learned from studying patients with cancer may also help us understand how the immune system responds to COVID and help in the development of new treatments. In fact, my group has been recruited to study these immune cells in patients with COVID-19 as part of a collaborative research project involving researchers and clinicians from Deakin University, Barwon Health and Ballarat Health Services.

There are media reports suggesting disunity in the scientific community about the AstraZeneca (Oxford) vaccine and whether it should be released. Are these concerns valid?
Vaccines usually take much longer than a year to get approved. Given the public health emergency with COVID-19, regulators are moving as fast as they can to get an effective vaccine approved. The priority remains that vaccines are safe and effective, but longer studies will help to refine the approach. For example, we know the AstraZeneca vaccine greatly reduces the likelihood of getting COVID-19 and almost eliminates the chance of developing serious illness if you do get infected. We also know the vaccine has an excellent safety profile. Collectively, this information has allowed emergency approvals of the vaccine in different countries, and Australia is likely to follow suit. Full approval though will require more detailed analysis to help optimise the vaccine strategy and clarify some uncertainties. For example, more tests are underway to determine the most effective vaccine dose and the time interval between vaccinations. We would also like to study people for longer to determine how long effective immunity lasts. In short, there are some areas where we are still gathering information and it may be possible to make the AstraZeneca vaccine more effective, but there is no doubt that it works and is safe.

The latest controversy is partly about whether we should wait to answer all questions before approval, and if this vaccine can achieve herd immunity in Australia. As mentioned above, the key questions about safety and efficacy have already been answered and the urgency of the pandemic means we can move forward and refine our approach as more data emerges. The situation with herd immunity is slightly different. Viruses need to keep infecting new hosts to ‘survive’. Herd immunity occurs when the virus infects new members of the population, so it dies out. For COVID, full protection of the community is likely to require about 80 per cent of the population to be immune to the virus. It’s a big challenge and unlikely to be possible (logistically) until late this year at the earliest.

Some scientists have expressed concern that the AstraZeneca vaccine is only 60-90 per cent effective, so when combined with expectations that some people will not get vaccinated, it may mean the community doesn’t reach the ideal 80 per cent plus protection. This is possible and we may not become fully protected, but that is no different to the annual influenza vaccine, which is only about 50 per cent effective, yet very useful and strongly encouraged. The AstraZeneca vaccine provides better protection than the flu vaccine, is safe, available now and will stop many people dying, so there is no reason to lose confidence in the medical recommendations.

At the start of the pandemic, experts predicted a vaccine would be available in 12 to 18 months. It now looks likely several vaccines may be approved for Australia in coming weeks.  If so, are there any other obstacles to overcome?
It does appear that we are on the verge of having effective vaccines approved within 12 months of the projects starting. This is very exciting progress, but the logistics of delivering a vaccine to the community are a big challenge, especially as we are aiming to immunise more than 80 per cent of the population.

Once a vaccine is approved for use, it will take time to manufacture enough doses and to organise the delivery of the vaccine to the entire population, so I’m sure the government is hard at work to avoid a lag between vaccine approval and when the community actually receives it. We are likely to see certain groups – for example, health care workers and people at high risk of serious symptoms – given priority for receiving the vaccine before it becomes available to the wider community.

The most advanced vaccines seem to need multiple vaccinations, like measles and hepatitis B vaccines. Why?
Part of the reason that vaccine trials take a long time is that the protocol often needs to be modified to find the most effective approach. The most advanced vaccines (including the Pfizer, AstraZeneca and Moderna vaccines) need two doses to boost the immune response to the required level, whereas other approaches may only need one. Some one-dose vaccines are currently in late-stage trials so it is possible these will also prove effective.

While the effectiveness of the immune response is paramount, researchers and health officials also take into account the practicalities of delivering the vaccine because a requirement for two doses will inevitably result in fewer people being fully vaccinated, and can be a significant obstacle for vaccine programs in remote areas and developing countries.

Will a COVID-19 vaccine be long-lasting, like measles and hepatitis B vaccination, or require ongoing boosts, like seasonal flu or tetanus?
The short answer is that we don’t know. COVID-19 itself has been with us for less than a year and so it’s difficult to know how long a person will stay immune after they have been infected or following vaccination. The flu shot needs to be updated regularly because the strains of the virus change each year, so we are effectively fighting different types of flu viruses, so one vaccine isn’t enough for lifelong protection. For COVID-19, there are early signs that the immune system does retain ‘memory’ of the virus for at least a year, which is good news, but how effective or long-lasting it is isn’t yet known.

Immunisation is rarely 100 per cent effective across the whole community, so there could be difficult decisions ahead about which vaccine is approved for community use. In more normal times, pharmaceutical companies will test different forms and doses of a vaccine across all sectors of the community, for example, age, sex and race, to ensure the approved vaccine is safe and provides effective and long-term protection. In this pandemic, we are condensing this process to provide protection as soon as we are sure the vaccine is safe and effective, but it is likely that our protocols will be optimised as new data is received. It’s a difficult balance.

One current treatment for severe COVID-19 is a drug called dexamethasone, which is an immune suppressant. Why would it help to suppress the immune system when someone is suffering from a virus? Wouldn’t it be better to enhance the immune system instead of suppressing it?
A strong immune response to COVID-19 is important, but we are now realising that an excessive or prolonged reaction can be harmful to some individuals. Typically, this is happening when the initial immune response does not clear the virus, so the immune system escalates its activity, and this can lead to other problems. In those instances, doctors need to balance the value of a powerful immune response against the dangers of inflammation and in some instances, it helps to dampen down the immune system to prevent indirect harm.

Are there other immune-based treatment options in research phases to help prevent severe COVID-19 disease?
Immunologists are throwing everything at finding ways to end this pandemic and there are many potential treatments under investigation. The biggest focus is on vaccine development and several have already received emergency approval in other countries and others are at very late stages of testing, and there are many dozens more in development. There is good reason to expect that several of these will be effective, however, vaccines don’t help people who are already sick with the virus so many groups are developing ways to reduce the severity of COVID-19.

These treatments are not necessarily designed to cure COVID-19 but would make the disease far more manageable, much in the way that HIV has become a manageable disease despite the lack of a cure or effective vaccine. For COVID-19 though, we are optimistic that several effective vaccines will be developed, and there have already vaccines from Pfizer, Moderna and Astra Zeneca that reported impressive preliminary results for their trials and have received emergency approvals for distribution.

There have been many critics of the Russian vaccine trials. Why are people critical of this potential vaccine?
The results from this vaccine trial have been promising and they are using an approach similar to that of other groups, so there is optimism that the strategy they have used has a reasonable prospect for success. However, not all of the data has been made available to other researchers, so there are unanswered questions that would need to be addressed before the wider research community can fully appraise and endorse it. On the one hand, it is understandable that governments would want to develop and approve an effective vaccine as soon as practicable, but one of the reservations many people have is that vaccine trials are designed to identify adverse effects before it is approved for community use and this requires long-term monitoring of people who received the vaccines during the trial periods. For the Russian vaccine, and indeed any vaccine that is approved rapidly, the speed of the trial limits this long-term monitoring.

Are any of your collaborators working on COVID-19? If so, are they benefiting from the research that has come out of your lab?
I work with several groups at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, and the Murdoch Children’s Research Institute who are conducting COVID-19 research. Our collaborative work has helped in some of this research and we talk regularly to discuss results and new ideas, but those projects are managed independently of my group. I am also part of two studies of patients with COVID-19 involving researchers and clinicians from Deakin University, Barwon Health and Ballarat Health Services. One study examining the immune cells I mentioned earlier and the other (with Professor Fergal Grace and Dr Matt Wallen from Federation University) is examining the changes in lung function of patients during the recovery from COVID-19 infection.

A vaccine may not be available to a large proportion of our population in the short to mid-term, so what are the best strategies that we can employ to live with this virus in the community?
Until the whole population is immunised, the most important thing is to reduce transmission within the community. To do this, we need to identify areas of greatest risk and modify our behaviour to reduce the chances of infection. This can take many forms and some will be specific to particular settings; for example, new workplace safety guidelines will be needed for some industries, but we can all reduce the risk of transmission by social distancing, disinfecting hands and surfaces, wearing masks, and most importantly, getting tested for COVID-19 if symptoms arise and quarantining when you are waiting for test results or when you are infected. A big advantage we have is that most people can recover from COVID-19 quickly in their own homes, so if they self-quarantine at the first sign of infection or exposure to an infected individual, this will help to avoid infecting other people and outbreaks of the virus can be snuffed out entirely rather than spreading. If we can do this across the community, then the virus is entirely manageable.

Professor Stuart Berzins is Professor of Immunology in the School of Science, Psychology and Sport. He leads a group that studies the regulation of human immune responses in cancer and other settings in collaboration with clinicians and research groups from other scientific institutes.