Vaccine concerns are understandable, but misplaced | Charles Mallia Azzopardi

The new COVID-19 vaccines have raised hopes for an eventual end to the crisis; but have also been met with scepticism.  Dr CHARLES MALLIA AZZOPARDI, head of Mater Dei’s Infectious Diseases Division, allays fears that the approval process may have been rushed

 Charles Mallia Azzopardi (Photo: James Bianchi / MaltaToday)
Charles Mallia Azzopardi (Photo: James Bianchi / MaltaToday)

As of this week, Malta has started to administer its first batch of the much-anticipated COVID-19 vaccine. Here as elsewhere, there are concerns about the speed with which this vaccine was developed and approved. Are these concerns justified?

The concerns, in themselves, are perfectly understandable. If you look at the normal timeframe in which a new vaccine gets approved, it usually takes around 10 years. In this case, the vaccine was produced and manufactured in about 11 months. So obviously, it raises the question of whether there was enough scrutiny to ensure that the vaccine is safe and effective in the first place. There is no denying that.

However, if you look more closely at the process itself, you will see that this did not come about at the expense of efficacy and safety. There are a number of issues which have resulted in this contraction. Starting with the pandemic itself: which, as the name implies, involves the whole world. As a result, there was a huge global effort - featuring unprecedented collaboration between governments, manufacturing companies and NGOs – to try to suppress this disease.

So where, usually, a lab would work on a new vaccine in isolation – and try to keep it secret from other labs, for obvious reasons – this did not happen, in this case.

Moreover, the usual process is for a manufacturing company to go through a number of phases, involving volunteers in increasing numbers. In Phase One, there might be 10 volunteers; in Phase Two, a hundred; and in Phase Three… tens of thousands.

Organizing these trials, therefore, inevitably involves huge amounts of money. So what usually happens is that, if a new vaccine shows promise at the clinical (lab-based) stages, the company will have to first seek financing. That, alone, usually takes a couple of years.

In this case, however, world governments were under intense pressure; and they decided to invest the necessary money - with no guarantees attached - to make sure that the manufacturing company would not run into financial problems. The EU alone invested €3 billion; the USA, €5 billion… apart from other countries, naturally. This, too, shortened the process considerably…

What about the medical studies themselves, however? How is it possible for a process which normally takes 10 years, to be concluded in 11 months… without taking short-cuts?

There are other factors involved: and one of them (ironically, perhaps) is the extent of the disease itself.

To conduct large-scale, robust studies - and to produce positive results – you not only need huge amounts of volunteers; but also, a huge number of infections. If, for instance, we are dealing with a disease that only affects five people a week… it would take a number of years to conduct the necessary tests, on tens of thousands of people, to ensure a positive outcome.

But because this pandemic is causing millions of infections every week, this process was considerably reduced. There are so many infections, that you can reach the significant amount of volunteers, needed to come up with a significant answer, within a much shorter time-frame…

Another factor concerns the ‘rolling review’. Once the necessary studies have been conducted – and thousands of pages of data have been compiled – what usually happens is that the data is passed on to the regulatory agencies, at the end of the entire process.

In Malta, the regulatory body would be the Medicines Authority; but internationally, the three main ones are the Food and Drug Administration; the European Medicines Agency; and the Medical and Healthcare Regulatory Agency.

Under normal circumstances, it would take at least a few years for these agencies to be able to come up with a final ‘Yes’ or ‘No’. This is because the standard procedure is for all the data to be collected first, before being submitted for approval.

In view of the urgency in this case, however, the agencies decided to accept data, not at the end of the process… but as it came out of the studies, phase by phase. As the data is produced, it is being immediately passed on to the regulatory agencies so they can start working on it. So it’s a rolling review… it’s not a case that the reviews are not taking place; they are, as they should be. But instead of waiting for all the data to be collected… the data is being analysed, step by step, as it emerges.

Lastly, what happened in this case – which doesn’t happen usually – is that, because the companies involved had access to large sums of money, they started to produce the vaccine, and to stockpile it in their stores, before getting final approval by the authorities. For obvious reasons, this has never happened before; because it’s a huge financial risk. But this time round, the money they were risking was not their own. It was our money…

So if I’m understanding correctly: had this vaccine not been approved, all those stockpiled drugs would have gone to waste…

Exactly. They would have to be destroyed. However, the corollary to this is that: if the vaccine was found to be safe and efficacious – as, in fact, it was – the producers would be in a position to start rolling it out immediately.  And this is precisely what happened.

So when you consider all those factors, it explains why the process has been contracted in such a way as to not impact the product’s safety and efficacy: which has been proven through all these studies.

As things stand, the vaccine has been rolled out, and has already been administered – in Malta as elsewhere – on a small number of patients. On the basis of what you’ve seen so far: do you think the decision to approve the vaccine was justified? Is the vaccine actually working?

Up to now, we have not seen any severe side-effects in Malta; and even looking at the thousands of people who have been vaccinated in other countries, there were no reports that were worrying.

Obviously, however, there is a degree of risk involved in everything we do in life. What is important, then, is that we try to reduce the risk as much as possible. In this case, the balancing act is between the ill-effects of COVID-19, as opposed to the possible ill-effects of the vaccine itself…

The problem there, however, is that while we all know the ill-effects of COVID-19… the possible side-effects of the vaccine remain unclear. There have been reports of allergic reactions, for instance. How serious would you say these possible ‘ill-effects’ might be?

Unfortunately, the issue of allergies has been blown out of proportion. What happened in the UK, for instance, is that – a couple of days into the vaccination process – there were a few severe reactions. Now: when it comes to the COVID-19 vaccines, there are only two major, absolute contra-indications [i.e., reasons not to take the vaccine]: the first is when someone gets a severe reaction to the first dose – and by ‘severe’, I mean ‘needing hospitalisation’; the second (which is related) is whether the recipient is known to have any allergies to any of the components of the vaccine.

Compared to other vaccines, however, this one has far fewer components that are known to cause allergic reactions. It has no egg components; no anti-biotics… so while the risk of allergic reactions remains a factor – it always does - it is actually much lower, in this case, than with other vaccines: including, for instance, the influenza vaccine…

Let’s turn to how it actually works. My limited understanding is that the COVID-19 is ‘mRNA-based’; and that the vaccine operates by emulating the properties of m-RNA, to induce the body’s immunity system to recognize its presence, and respond accordingly. This has led to the assumption that the vaccine may end up ‘modifying our DNA’…  with possibly frightening consequences. Are these concerns in any way justified?

For a vaccine to ‘modify our DNA’… it has to enter our genetic make-up in the first place. What does that mean? Let me explain it this way: the cell is generally shaped like a ‘ball’… and inside this ball, there is another sphere called the nucleus. That is what contains our genetic material.

Now: these ‘messenger-RNA’ vaccines do not enter the nucleus. They stay outside the nucleus, in a jelly-like substance known as the cytoplasm. And after they’ve done their job, of producing the shell of the coronavirus, they are destroyed within a couple of days. So our clear understanding, as things stand, is that these these m-RNA vaccines cannot affect our genetic make-up. This issue has obviously also been carefully considered by the regulatory bodies.

It’s worth mentioning, however, that there are other vaccines – some of which are still awaiting approval – and these may use other methods. But the ones which are available in Malta – namely, the Moderna and Pfizer vaccines – are both m-RNA-based.

All the same, however, it appears that this approach to vaccination – which is unlike the traditional models – has never been used before. What makes medical science so sure that it will work according to plan?

It is true that we are talking about a new, ground-breaking technology; but it is equally true that the scientists did not start from ‘ground zero’. COVID-19 is not the first disease to be approached this way: m-RNA-based technology has already been used in the case of influenza, the Zika virus, and in other areas of medical research, such as cancer treatment. The difference, however, is that it has not so far been tested on thousands of people.

But this also has to be seen in the context of the entire world having been brought to its knees. To put it another way: it is like being chased by a rabid dog, and your only option, to avoid getting bitten, is to climb a tree. You have to decide: are you going to climb that tree… with the risk of being bruised by a branch? Or possibly falling out of it? Or do you stay there, and wait to get attacked by the dog?

I, for one, would certainly take the decision to climb the tree. Because at the end of the day, this is about risk assessment. To use another analogy: it’s like crossing the road. Do you decide not to cross a road, because there is a chance of being run over? Or do you look right and left, and assess the risk before taking the decision?

It’s the same with this vaccine; and any vaccine, for that matter…

Meanwhile, we are hearing of ‘variants’ of this virus… including a more infectious strain, originating in the UK, which is now present in Malta. Is there any reliable evidence that the vaccine will work against new (and future) variants, too?

Up to now, what we know about these new variants is that they are more infectious; but they do not cause more severe symptoms. In other words: we are still talking about the same virus… only, a variant that spreads more easily.

So there is no real reason to suppose that the vaccine should be any less effective. At least, not in the case of the variants we know about so far.

All this can change, however.  We might face new variants that do cause more severe symptoms; or which, for instance, affect younger people.  Even if that does happen, however, it doesn’t mean that the vaccination ‘will not work’.

Having said this: we still need more studies today. And studies are still being carried out, all the time. It’s an ongoing process…

One last question: our hopes of a ‘return to normality’ depend largely on the success of this vaccine. All things considered: how hopeful are you, in reality?

At this stage I would say that I am optimistic: the reason being that we have followed this very closely over the past 11 months; we have met the regulatory bodies online; we have seen the evidence, and the studies… and in conclusion, everything is pointing towards a safe and effective vaccine, which is going to be a game-changer, and eventually bring an end to the pandemic.