Do booster jabs have the potential to break the 4th wave? Why are they necessary and how do they work? Luxembourg epidemiologist Joël Mossong has the answers.

The Covid booster has been held up as a longed-for breakwater as the fourth wave of the virus swept over the globe. Science.lu turned to epidemiologist Joël Mossong for more information on the boosters and why they are so vital to the fight against coronavirus.

Joël Mossong, do you think the booster jabs are necessary?

JM: Yes. I think they're particularly necessary right now so we can get a grip on the situation as we head into winter. We are currently seeing the effects of the boosters in retirement homes. The third jab was administered to residents in care and retirement homes back in September, and now we are seeing very few cases of the virus in these environments. The majority of cases linked to retirement homes are found among staff, many of whom have not had a booster.

Currently, more and more vaccinated people are being hospitalised. Why is this the case?

JM: At the moment around 70% of the population is vaccinated. In absolute terms, it's clear that is why the number of vaccinated people in hospital is rising. However, we also regularly calculate the incidence separately for vaccinated and un-vaccinated people, by dividing the absolute number of cases by the respective number of those vaccinated or un-vaccinated. In doing so, you can see that the relative incidence in those who have been vaccinated is two to three times lower than in those who have not been vaccinated. Un-vaccinated people are still two to three times more likely to end up in hospital.

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Copyright: Tom Goedert, statistician. The graph shows that the incidence rate among un-vaccinated people for calendar week 34 was more than five times higher than the incidence rate among those who were vaccinated. As of today (week 47) the incidence of the un-vaccinated is more than twice as high as that of the vaccinated.

JM: That's one reason. The other is based on experiences with vaccinations around the world over the last few months, which clearly show one thing: the vaccine's immunity decreases over time. Particularly when it comes to an infection. A few months post-vaccination,  the antibodies will no longer suffice to avoid infection if the person comes into contact with the virus. However, most of the time, the infection and its effects in vaccinated people are relatively mild. Additionally, the risk of severe virus effects increases with age, even if a person is vaccinated. However, it is generally worse for un-vaccinated people


As this graph shows (Tweet dated 4 November 2021, based on a study by Peter Nordström), the effectiveness of vaccines decreases over the months that follow. Especially for the AstraZeneca jab, protection against infection decreases very sharply, so that after 4-6 months there is hardly any protection against infection. That is why the Luxembourg government has now made it possible for everyone who has been vaccinated with AstraZeneca to receive a booster vaccination after just 4 months. According to this research, Moderna has the best vaccination protection against infection, the second best is cross-vaccination Astrazeneca (1st dose) & Moderna / Biontech (2nd dose). Important: this is about protection against infections, which is decreasing. The protection against severe gradients remains high.
 

The graph is based on the study "Effectiveness of Covid-19 vaccination against risk of symptomatic infection, hospitalization, and death up to 9 months: a Swedish total-population cohort study", by Peter Nordström, MD, PhD, Marcel Ballin, MSc. , Anna Nordström, MD, PhD.

The following graph shows that vaccination effectiveness is declining in Luxembourg as well. Do you have any comment on this?

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Copyright Tom Goedert, Quellen: ECDC, Ministry of Health Luxembourg

This graph does not cover clinical studies, but practical data amassed in Luxembourg. Therefore, some elements are not taken into account, such as varying text frequency between vaccinated and un-vaccinated people, as well as differing behaviour.

JM: The graph shows that even immediately after vaccination, protection from infection does not reach 100%, and it reduces over time. Protection against severe effects and hospitalisation also decreases quickly. However, when checking a treatment graph for intensive care, you need to be careful. There isn't enough weekly data, and it's possible that you would see big fluctuations. A single new case could massively affect the diagram with its fluctuations.

*Note from Science.lu: The fact that protection is less than 100 percent at the beginning was already clearly stated in the clinical studies. In these, depending on the vaccine, an effectiveness of approx. 65 to 95% was achieved. 
 

Could it have been foreseen, that efficacy would drop so quickly?

JM: In the beginning it was said indirectly, but it wasn't proven until the first clinical studies were carried out. They lasted around five or six months though. Nevertheless, it was assumed at the time that the protection would last for a relatively long time - it was only later that researchers discovered the vaccination protection was decreasing faster than expected. But this mainly affects the aspect of infection. If you consider the protection against severe illness, the expectations of that time have been fulfilled.

We have a whole range of existing vaccines for other illnesses which need three doses for primary vaccination. Some also need boosters at regular intervals in the future. Can it be assumed this will be the case for Covid vaccines? 

JM: I think it's hard to make that assumption, as the majority of Covid vaccines are new concepts. We had relatively little experience with them at the start of the vaccine campaign. Now, for inactivated vaccines, you need multiple doses to establish basic vaccination. Some of these will also need regular boosters. With live vaccines, you need fewer doses, because the immune response is generally stronger. Take measles as an example - 90% of vaccinated people build up good immunity after just a single dose. The second isn't really a booster as such, but instead protects the minority of people who didn't respond adequately to the first dose.

The mRNA vaccines represent a new concept, so we don't have the long-term experience on the number of doses required to establish a lengthy protection. This isn't limited to Covid vaccines though - with papilloma viruses, it was also assumed that we would need three doses for vaccination, but now two doses are recommended. Clinical studies cannot test every single possibility - this sort of data can only be gained through experience over a lengthy period of time.

Note: This is how many doses are required for selected vaccines.

The Quarks science department has compiled how many doses are required for some selected vaccines. There are a number of vaccines that require three doses of vaccine.


Copyright: Quarks, Tweet dated 12. November 2021

As an epidemiologist, do you believe the booster will help to break the fourth wave? 

JM: Yes. For me it's clear that the boosters will help - we saw their efficacy in Israel. It wasn't possible to vaccinate the whole population, but they were able to get the summer wave under control through vaccinating a high percentage of people. This is why I believe the boosters will be so important for us here in Luxembourg, so we can control the wave in winter. The faster we act, the more likely it is that we will get through the winter.

You mention Israel - how did they go about implementing the boosters and what effects did it have on the fourth wave there?

JM: Israel led the way in terms of vaccination progress for a long time. But over the summer it became clear that a new wave of the virus was approaching. The authorities came to the conclusion that a booster jab would be required, which they rolled out fairly quickly and extended to the whole population. The effects of this did not stop the wave immediately, of course, but it shortened it and also reduced the overall spread, so it did not hit so hard. In Europe, the results of the studies weren't considered correctly at first, because some of them did not meet international standards 100%. But I think that in the meantime, European and American authorities have agreed that the Israeli method made sense.

What exactly happens in the body to make the booster so effective?

JM: I'm no immunologist, so I can only speak from an epidemiology perspective. In the epidemiological data we can observe a very rapid increase in antibodies, to a higher level than with the second dose. We see an effect here after a few days and not after two weeks as with the second dose, so the immune defence rises faster. A high antibody level can be observed after just one week. In comparison, this took two weeks after the second vaccination.

The mRNA vaccines seem to have stronger side effects following the second dose. Is this the case for the third dose as well?

JM: I'm not aware of any scientific studies on this. From experience, we've heard there are fewer vaccine reactions with the third vaccination than with the second dose. However, we simply still lack the data to support this observation. But we also see that the incidence rate among "boosted" people is two to three times lower than in those who received two doses.

At first it was said that two doses would be sufficient; now six months later, we have the boosters. What would you say to people who feel misled by initial promises?

JM: I think expectations were set too high at the beginning of the vaccine rollout. But the situation has clearly changed. When the vaccines started to be administered early this year, we didn't know as much about the efficacy and how long they would be effective for. Now we can see that boosters are needed. Of course, it's hard to convey this. But the virus is still dangerous and we still don't know enough about it, or enough about preventing it. But we are learning as we go, so it's important to make use of what has been learned.

When is the next booster likely to be necessary?

JM: I strongly believe we will need at least one or two more boosters. We'll have to see if they are required. Currently, data suggests the third dose will last longer than the second. Whether it will last until next winter, remains to be seen.

The new Omicron variant that is currently in circulation is a cause for concern for researchers around the world. The fear is that the many mutations in the spike protein could bypass the immune response of vaccinated and recovered people.

Since the Omicron variant has a large number of mutations, one can assume that this variant can bypass the immune response better than Delta, for example. What exactly these differences will look like, and whether the vaccines still protect, we will find out in the next few weeks as researchers are working round the clock to answer these questions.

However, we can't forget in Europe that the Delta variant is a much more important challenge. We don't have enough evidence yet to tell whether Omicron will win the race against Delta this winter. It is therefore important that as large a proportion of the population as possible protects themselves against Delta with a booster. With a little luck, this will also help against Omicron. If a new vaccine against Omicron specifically was needed, it would take a few months before it could be manufactured in large quantities.

Note from Science.lu: The Omicron variant is currently causing a stir around the world. It has the potential to be very contagious and possibly displace Delta. However, this has not yet been proven and will only become apparent over the next few weeks. What has also not yet been proven is how dangerous the new mutant is. It may be worse, about the same, or far less severe than the Delta variant. In the latter case, this could help to make the pandemic much easier to cope with if, for example, the number of severe courses were drastically reduced. So the advent of a new mutation is not necessarily bad news, it can also be good news, Epidemiologist Catherine Bennet stated in an interview : "There is a possibility that we will see a more infectious and less virulent version of the virus, which would be one of the steps towards a happier life with the virus. We have just as much evidence that the new variant might be okay as we have signals that it might be a bit unsettling. "  

We are now administering the third set of jabs, while in poorer countries fewer than 5% of the population are fully vaccinated. In your opinion, what is more important: vaccinating poorer countries faster, or pushing the booster in wealthier countries? 

JM: Both are extremely important; but also very difficult to implement. On the one hand, the World Health Organization says we shouldn't offer boosters as long as people in poor countries haven't had the chance to get a vaccination. On the other hand, it is very difficult for politicians to supply the vaccination doses to poorer countries while locking down their own people.

In addition, little information is available about the Covid situation, especially for countries in Africa. We know very little how the virus circulated there. It has always been said that the virus did not spread as widely on that continent, but the few virological studies that exist point in an entirely different direction. It would seem that the virus has already circulated violently in many African countries, but they did not have the laboratory capacity to determine this. In addition, the age structure in these countries is such that, from a virological point of view, you cannot expect a high mortality rate which would then reveal the spread of the virus, because the proportion of young people in Africa is very high. All of this makes it extremely difficult.

How does it work for the booster? Can you do walk-ins or do you need to wait for an appointment?

JM: For the two mRNA vaccines, it's recommended that people receive a booster after six months*. For people who received AstraZeneca, the recommended gap is four months. Invitations will be sent after that point, but you can also visit your GP for the jab after the gap has concluded.

The second dose for Johnson & Johnson isn't exactly a booster - instead it should be seen as a second dose, similar to the other vaccines. Based on today's data it is recommended that people should get this second dose if they received the J&S jab first.

Personally, I recommend everyone should get the booster as quickly as possible. It is the most useful contribution anyone can make to help us get through the winter months without major restrictions.

*Since this interview, the Luxembourg government has amended the gap to five months, reducing to four months from January 2022.

Author: Kai Dürfeld (for scienceRELATIONS - Science Communication)

Co-Author, Editor: Jean-Paul Bertemes (FNR)