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

Promising trials have shown that an effective vaccine may be available sooner than first expected.

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

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.

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 are already at very late stages of testing, but there are many dozens more in development. There is good reason to expect that one or more of these will be effective, however, vaccines don’t help people who are already sick with the virus so many groups are also developing ways to reduce the severity of COVID.

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 an effective vaccine will be developed, and there have already been highly promising announcements from Pfizer and Moderna reporting impressive preliminary results for their trials.

At the start of the pandemic, experts predicted a vaccine would be available in 12 to 18 months. In your opinion is this realistic? If so, is it on track?
While no one can be sure until all of the necessary trials have been completed, the progress to date has been good and immunologists are generally optimistic that an effective vaccine will be developed and approved soon. As the recent announcements for Pfizer and Moderna have shown, 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 a big challenge remains the logistics of delivering a vaccine to the community.

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 this is likely to see a lag between the time of vaccine approval and when the community actually receives it. We are also likely to see certain groups – for example, health care workers – given priority for receiving the vaccine before it becomes available to the wider community.

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.

Would you think that a vaccine would be a single shot vaccine, like seasonal influenza, or a regime of multiple vaccinations, like measles and hepatitis B vaccines?
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. Some of the current vaccines in late-stage trials (including the Pfizer and Moderna vaccines) need two doses to boost the immune response to the required level, whereas other approaches may only need one. Other variables can be the requirements for storage. In general, mRNA vaccines such as the Pfizer and Moderna vaccines are more difficult to store and transport because they need to be kept at very low temperatures. This can complicate efforts to distribute the vaccine widely.

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 refrigeration is an issue for vaccine distribution in remote areas and developing countries.

Would 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 life long protection. For COVID-19, there are early signs that the immune system does retain ‘memory’ of the virus, which is good news, but how effective or long lasting — that 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 a pandemic, should we condense this process to provide protection as soon as possible, or should we conduct extensive testing and ensure the best and most effective vaccine? It’s a difficult balance.

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.

If a vaccine is not available in the short to mid-term, 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 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 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 quickly in their own homes, so if they are careful to avoid infecting other people, that outbreak of the virus can be snuffed out entirely. 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.

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