Dr Steffen Thirstrup took up the role of the European Medicines Agency’s Chief Medical Officer at a crucial moment in the brief history of the Covid-19 pandemic. Vaccines had helped to drive down hospitalisation and deaths, but cases were still high and new variants of the virus were emerging.
A key driver of those early summer spikes in case numbers were the Omicron BA.4 and BA.5 variants which, although apparently milder than some of the viruses that had previously become dominant, were highly infectious and continued to cause serious illness in some patients.
Vaccine developers were busy compiling data on adapted vaccines designed to protect against the original SARS-CoV-2 virus and Omicron BA.1 (which was first identified in South Africa in late 2021) while working on newer vaccines aiming to protect against the original virus and BA.4/5.
Now, as autumn arrives, European countries have new and approved vaccines to offer as part of booster programmes which, they hope, will make this winter brighter than than the last two.
For Dr Thistrup, a doctor, scientist and seasoned regulator, it has been a busy start at the EU watchdog. Vaccines Today asked him to outline how the EMA approached the task of reviewing adapted vaccines, why protecting against the original strain is still worthwhile, and if we might expect the process for reviewing future adapted Covid vaccinesto mirror the regulatory approach taken to the annual flu vaccine.
- European regulator has approved vaccines offering combined protection against the original Covid-19 virus and Omicron variants
- Adapted vaccines offer broad protection and offer reassurance should new variants emerge
- The SARS-CoV-2 virus is still changing – more adapted vaccines may be required in response to future variants
- If you have not had a Covid-19 vaccine, get it now; if you have had your first course of vaccines, you may soon be offered a new booster dose
Transcript: Vaccines Today interview with Dr Steffen Thirstrup
Why did the EMA take longer than the US FDA to approve the BA.4/5 vaccine?
I would not consider the difference in approval time –approximately 10 days – of the bivalent original/BA.4/5 between EMA and FDA as having any significant impact on public health. Member States in the European Union have just started rolling out the booster vaccines and both the BA.1 and the BA.4/5 adapted vaccine will be available in due time for national roll-out.
The FDA decided to focus only on the bivalent original/BA.4/5 vaccines whereas we, in Europe, wanted to give the Member States a wider range of opportunities for the autumn revaccination campaigns.
Can you explain the different approaches given that regulators have access to the same data?
It is indeed correct that FDA and EMA have been looking at the same set of data. FDA also used the human immunogenicity data from the adapted BA.1 vaccine (as well as data regarding other experimental vaccines) to approve the bivalent original/BA.4/5 vaccine, but they did not approve the bivalent BA.1 version as a separate product.
In the EU, we took a stepwise approach approving the BA.1 adapted vaccine shortly before the adapted BA.4/5 version. The difference in time between our approval of the two different versions also stems from the difference in the timing of the submission by the applicant.
Regarding the EU position to give the Member States a wide range of vaccines for the autumn, I would also remind you that we are still reviewing other potential booster vaccines from other manufacturers. Our human medicines committee is progressing with the assessment of these applications but there are still some aspects to be discussed before it can reach an opinion.
Why do the latest vaccines include the original virus if it is no longer circulating?
This is an important question – onethat has been discussed extensively also in the international fora with other worldwide regulators and with the scientific community.
We know that the original vaccines still provide a good protection against severe disease and hospitalisation. The fundamental concept is ensuring that the breadth of the immunity of the boosters is as large as possible. Data show that this goal can be achieved by including the original strain as part of a booster vaccine.
Omicron – and its subvariants – and the original strain are very far away from each other in immunological terms so keeping a breadth of immunological protection from a bivalent original/Omicron booster will give some reassurance that if new SARS-CoV-2 variants (different from Omicron) emerge during the autumn/winter 2022/23, there is a better chance that an adapted booster will provide additional protection.
That was the first consideration among international regulators. The second one is that if we think that in the future, we might want to restrict the amount of different compositions of vaccines and formulations available, probably a bivalent vaccine could be a good starting point also for primary vaccination. Of course, we will have to learn more about the performance of these adapted booster vaccines before determining what could be the best way forward for the future.
What advice can you offer to people this winter who might be considering having their next Covid booster?
If you have not yet received a primary series of the vaccine, you should get it now. The most recently approved bivalent original/Omicron vaccines have been studied, evaluated and authorised for revaccination and not for the primary vaccination.
If you have been given the primary series of the original vaccine and are among those (immunocompromised, people 60 years of age and older, and vulnerable populations) who are eligible for a booster, you should take the adapted bivalent original/Omicron vaccine that your national health authority is offering.
Is a BA4/5 vaccine preferable or are all boosters likely to offer protection against serious disease?
Both the original/BA.1 and the original/BA.4/5 adapted bivalent vaccines are expected to expand the immunity against variants of concern, especially Omicron and related sublineages, no matter which variant of concern has been incorporated in the vaccine.
Moreover, as the BA.4/5 wave is gradually subsiding in Europe, a new variant may emerge and having a broad immunity will be important. Your national health authority is best suited to assess your needs and will take into account all the relevant criteria, such as your vaccination status and your health records.
We do not recommend waiting for a specific vaccine. Our experience with Covid-19 so far has shown that timely roll-out and focus on vulnerable groups has been more important in the success of vaccination campaigns than the use of one vaccine over another.
In your opinion, is it likely that the review of adapted vaccines will become an annual process like the flu vaccine?
So far, influenza has been the only virus in which the antigens are constantly changing on an annual basis. Therefore, the influenza vaccines have been rapidly adapted annually based on global knowledge of the circulating strains. For other infectious diseases, where vaccines are available, the situation has so far been very different, and therefore we have not been exposed to a situation by which we had to constantly change the composition of these non-influenza vaccines.
Frequent change of antigens is indeed a feature of respiratory viruses and it looks like, at least for the time being, that SARS-CoV-2 will fall into this category. We will need to adapt the vaccine against the SARS-CoV-2 virus to improve the immunity raised by vaccination, in order to be as close as possible to what is in circulation.
Whether this can be done on an annual basis as for the influenza vaccines, or if this has to be more random – based on change in circulating variants of concern – we do not really know at the moment. Development of vaccines with a broader protection (i.e. not needing regular adaptation) than what is being provided by the current armamentarium of SARS-CoV-2 vaccines is, at least in theory, another option that we might see in the future.
How might this experience make the approval of future adapted vaccines quicker?
We are on a learning curve with regards to rapid adaptation of the SARS-CoV-2 vaccines. The approval of both the BA.1 and the BA.4/5 adapted bivalent Covid-19 vaccines have given us further understanding of the virus and in particular the mRNA vaccine platform.
Real-world data from the currently ongoing/planned roll-out of the boosters will give us additional confirmatory data on the extent in which laboratory/animal data will be sufficient to rapidly adapt the vaccine.