Activity Transcript

Karine Lacombe, MD, PhD: Hello. I'm Karine Lacombe, MD, PhD. I'm a professor of infectious disease at Sorbonne University. I'm also the head of the infectious diseases unit at Saint-Antoine Hospital in Paris, France. Welcome to this program titled “COVID-19 Vaccine Clinical Compendium: Comparing Vaccines, Safety Status, and Future Perspectives”. Joining me today are Dr Jörg Schelling, MD, who is also a professor in general medicine and works at LMU Munich in Munich, Germany, and in his own private practice in Martinsried and Dr Anna Goodman, FRCP, who is an infectious disease consultant at Guy’s and St Thomas’ NHS Foundation Trust in London, UK. Welcome.

In this program, together with my colleagues, we will be discussing 4 points: COVID-19 vaccines authorized for use and why different vaccines are needed; how COVID-19 vaccines differ in terms of efficacy, safety, and acceptability; what the available vaccines can offer; and finally how to communicate with your patients about vaccination options.

Let's first see: what are the vaccines that are currently authorized for use worldwide? Worldwide we have 49 vaccines that have been approved by at least one country, as you can see on this map here. Just a few of them have been approved by EMA. They are circled here on this slide. Now I would like to ask Anna if she can briefly tell us why we need multiple vaccines for COVID-19.

Anna Goodman, FRCP: For COVID-19, obviously we're vaccinating the whole world. We need to have a very large supply with all different types of vaccines so that we're never in a situation where we don't have a vaccine for a particular individual. There might be somebody who can't have one type of vaccine for one reason or another. We need to be sure that we can offer different people a range of vaccines so that nobody is unable to be vaccinated. We're really in that situation already, but we also need to make sure that because we need billions of doses, we have a good supply chain and that we have vaccines that are going to work, as most of them seem to in all different subpopulations, such as those with underlying immunocompromise, pregnant people, and people in different age groups. We're fortunate in that the vaccines that have been licensed tend to work across these different range of conditions and situations.

These are all the vaccines that have been approved and are used. We've evaluated them in phase 3 trials, but they're not the only outcomes that we consider when we're deciding what vaccines to procure. For example, there might be considerations of storage or cost or logistics. We need vaccines that can support everybody everywhere. One example of that that's been used is a consortium called COVAX who have tried to make sure that the vaccines are really accessible throughout the world from making sure they're affordable, that they can be deployed correctly, and that the development processes are rapid and effective and not too expensive. In summary, a range of vaccines widely available.

We then have the consideration that there are different emerging strains. Like any respiratory virus, we've seen that SARS-CoV-2 changes over time. We've seen that this means that we want to have new vaccines as we have new strains of the virus. The emergence of new variant strains has had an effect on some of the vaccines that we've developed. We've been fortunate that some of the primary courses have remained effective, but can be made more effective with booster doses and vaccines focused on new strains. For example, we now have a situation where there are the variants of concern where the vast majority of COVID is now Omicron across the EU and the EEA. That's currently mostly BA.4 and BA.5 with subvariants, in particular such as BAQ.1 and BAQ1.1. The key thing is for our vaccines to keep up with these changes in the virus.

Dr Lacombe: Thank you, Anna. I would like to turn now to Jörg and ask you to provide us with an overview of the efficacy and safety of the COVID vaccines currently approved by EMA.

Jörg Schelling, MD: Well, thank you, Karine, for giving me the opportunity to talk a little bit about those 2 aspects. Being a practicing doctor, I was very happy to see all the efficacy data of all the vaccines because compared to what we know from influenza vaccines, the efficacy is good in every vaccine that is on the market in the European states. We know that there's efficacy above 90% in the Moderna and Pfizer vaccines, but also quite good in the Novavax vaccines, going down a little bit around to 70% or 66% for the Janssen and the AstraZeneca vaccines which are vector-based. But basically, all of the vaccines work better than other vaccines that we are used to when it comes to respiratory diseases. The efficacy is good, and of course, this has something to do with new technologies that have been invented in this situation. But still, as you can look at the data shown on the slide here, it's all very, very good compared to what we've seen before.

This is also true when we look at the mortality and on the vaccine efficacy on the symptomatic COVID-19 and severe COVID-19 cases. We see that there's a good protection from all the vaccines in preventing infection with SARS-CoV-2, but especially also the vector vaccines have a good protection rate against mortality. All the vaccines are working quite well, and especially when it comes to severe COVID cases, hospitalization and death, they all work in a good way. We've all used them with confidence for really protecting the patient from those severe outcomes.

Still, we had the change of the variants, as mentioned before. With those high numbers of 95%, 96%, 97% starting in the beginning, it has declined a little bit with Omicron. As you can see perfectly on this chart, it ended up being around 70% for most of the vaccines. With the 2 vaccines that started out with not so high protection rates, it still came down to this range about 60% to 70%. But this is still, from my point of view, very, very good efficacy considering the fast changes that COVID made in those 2 years or almost 3 years that we have known about this virus. I think even though there is a change, even though there is a change in the effectiveness, it's still very, very good rates.

There's another vaccine which was not mentioned on the slide before. The reason for that is simple, because there is no real efficacy data because the Valneva vaccine was put on the market or tested in comparison to the vector-based vaccine by AstraZeneca. It showed that the geometric mean titer antibodies for this vaccine were higher than the AstraZeneca one. Its efficacy is supposed to be somewhere above those 60% or 70% of the AstraZeneca one, but we don't know exactly where it's standing because we don't have any real efficacy data so far. But it's also in the same range and the same league than the others. It's definitely not below 50%. I don't know if it's 90%, but it's somewhere in between. It's working well, being a whole virus vaccine.

You've also asked me about the side effects, which are important for daily work and for the practice, and also of course for the patients. We know that most of the side effects tend to be mild, temporary, and like those experienced in other routine vaccinations as well. From my personal experience, I think the side effects after the booster doses are a little bit less than after first doses, but this is maybe something that cannot be looked at from an epidemiological point of view. But just from my personal experience in the practice, we know that after the second shot booster, the most frequent side effects are fever, headache, fatigue, and of course pain at injection side. But these are basically the side effects we know from every other vaccine when it comes from influenza to zoster to tetanus, it's basically all the same and there has not been a lot of difference when it comes to the new vaccine technologies.

Well, let's talk about the rare series of adverse events now, which are the ones we are looking at more closely, both in the scientific community but also in the general population, and especially in the media. As we all know, some vaccines had some difficulty after media reports came out that there might be some serious adverse events. We know that all vaccines can cause anaphylactic reaction. It's the same with those vaccines as well, but it's not more common than in other vaccines that we use on a regular basis.

The interesting thing is the other rare cases of myocarditis and pericarditis, especially when it comes to young men. This led to some countries not recommending some mRNA vaccines to those under the age of 30 because of that. We don't know if it has something to do with the possible intervascular implications of vaccination, especially with young men who have a larger deltoid muscle. But this is an ongoing discussion, but an interesting one. We have to keep a close focus and then monitor it because, of course, this is something that is related to the mRNA vaccines, and we have to collect more reliable data on that in the coming days and in the future.

There's also risk of other severe events, one of them to pick out is Guillain-Barre syndrome, which can happen with the adenovirus vector vaccine. The greatest risk is for men who are over 50 years old, but still, it's a very, very rare, serious adverse event. Then we are also monitoring urticaria after the mRNA vaccines who might also be caused by a potential hypersensitivity reaction to the vaccine.

Dr Lacombe: Jörg, tell me, could you discuss the acceptance of different COVID-19 vaccines among unvaccinated participants with conditional willingness? What's your opinion on that?

Dr Schelling: Well, we know that the media coverage and the discussion in the public about the side effects has widely influenced the willingness of the patients to receive one vaccine or another in different countries. Also, there are some cultural aspects as well. As you can see on this interesting chart, the AstraZeneca vaccine was more commonly used in the United Kingdom where it was also developed together with the University of Oxford but was not used as much in some of the other countries. But where the mRNA vaccines were more popular and more accepted, and especially in Germany, for example, with BioNTech being a German company, that also had to do something with trust in maybe local companies, the same in the UK with the AstraZeneca one.

But you can see on the chart clearly the patients mostly put trust in the mRNA vaccine. Both the Moderna one and the BioNTech-Pfizer one were rated very high with Moderna being a non-European company, maybe less than the BioNTech-Pfizer one, which had sort of a European touch to it. Again, AstraZeneca and Johnson & Johnson had to deal with the media coverage in this discussion on the side effects, especially thrombogenesis and clotting. I think the acceptance was mostly concerning the mRNA vaccines.

Dr Lacombe: Oh, okay. Thanks, Jörg. That was very comprehensive. Anna, can you tell us, what can the valuable vaccines offer? Because there is the endless topic of discussion about the adaptation of vaccines to the ever-changing epidemiology. Can they be adapted to meet the changing face of SARS-CoV-2?

Dr Goodman: Yes, absolutely. From the moment the vaccines started to be developed for SARS-CoV-2, there was an awareness that in the future they might have to be modified. As I said earlier, because respiratory viruses change over time and just like every year we get a flu vaccine, there was an expectation that the SARS-CoV-2 might change. This means that the developers have been ahead and there are already bivalent vaccines that are now available and are being used this autumn that have been adapted to include Omicron as well as the original ancestral strain. Those are now being widely used as booster vaccines for the autumn. These new bivalent mRNA vaccines have been adapted to better match the circulating variants of SARS-CoV-2 and are expected to provide broader protection against different variants.

We're always chasing our tail a little bit. It's always going to take some time to develop something. Although the mRNA vaccines were incredibly quick, the mRNA bivalent boosters that we're using were developed with BA.1. We're now at BA.4.5. We're always trying to keep up with what's available. Currently, the available bivalent boosters that are being used that have been tested in clinical trials are the Pfizer-BioNTech bivalent booster. Just to be clear, the dose that gets used for that, Pfizer, originally you would have had 30 micrograms of the ancestral strain, but the bivalent, you get 15 of the ancestral strain with 15 of BA.1. There it's combined to give immunogenicity to both, but you don't get a higher dose in terms of getting all side effects.

Moderna, we moved to a half dose of Moderna at this stage of boosting. The original Moderna vaccines that were used for your first doses were 100 micrograms, but the boosters are 50 micrograms. For the Moderna, the bivalent booster has 25 micrograms of the ancestral strain combined with 25 micrograms of BA.1. Now so far, the BA.4.5, what people are doing is looking at the neutralizing activity of people who've been vaccinated using those vaccines, but we haven't got clinical trial data as such for bivalent boosters with BA.4.5 as yet. That will come.

What we have got is the data from the Pfizer trial, the submissions to the FDA where they used the fourth doses of bivalent or monovalent and compared these and found that the titers with respect to Omicron were higher when using the bivalent by approximately 1.5-fold. This was tested in adults over 55 and found that, again, there was good immunogenicity in older people. That was using a dosing interval of 6.5 months from the first booster to the second booster, which is approximately what the world is seeing with the spring booster followed by an autumn booster now.

The safety data from that trial was as expected and, as Jörg has mentioned, that we expect that there will be occasional rare side effects and commonly, pain at an injection site or swelling of the arm or a reaction locally, and that people will have tiredness, headache, muscle pain, and perhaps some fever after having their vaccination. Interestingly for the ChAdOx1 trial, there was actually a study to look at giving paracetamol, which didn't reduce immunogenicity for that vaccine, for the AstraZeneca vaccine, but did improve the symptoms after the administration of the vaccine and how people felt.

There's also been a trial of the Moderna bivalent Omicron booster. Similarly, this has shown enhanced immunogenicity including in people who've had prior infection. What's been interesting, the early studies in all the vaccines were done in people who hadn't had COVID, but of course now we're testing vaccines in people who have had COVID and reassuringly, people who have had COVID still get an increase in antibodies. It's just really important to reiterate to patients that having had COVID isn't sufficient, as some people believe, and that it's still important to have the primary vaccines, then booster vaccines, with very similar results in terms of the safety data, as you would expect.

Dr Lacombe: There is another issue that I would like to raise with you which is also very important, that's vaccine equity. Could you tell us a little bit where we stand with the COVID-19 vaccination and vaccine equity?

Dr Goodman: This is a really key thing worldwide. It's a global pandemic. So far, we haven't yet succeeded in vaccinating the world. I talked earlier about needing enough doses to vaccinate the world, but as yet we're not there, which is a shame given that how far we are now into this pandemic into our vaccines. We have approximately 3 in 4 people now vaccinated in high-income countries, but unfortunately in low-income countries, in some countries that's as low as 1 in 4 people being vaccinated. It's really important that we work to improve this disparity.

It's also one of the reasons that it's important to have all these different vaccines available, some of which might be cheaper, for example, easier to access in terms of their cold chain requirements, for example. I'm showing a slide that shows you the different cold chain requirements of different vaccines. Most of the manufacturers have worked very hard that even where there is a significant cold chain and need for minus 80 for example, there is then a phase where the vaccine can be stored in a special cool box for some time. I think the vaccine manufacturers are very aware of this issue. Those rolling out the vaccines globally, such as COVAX, are working really hard to make sure that we can get vaccines to all populations that need them and that the cold chain doesn't cause a problem for that.

Dr Lacombe: Can you remind us which vaccines are authorized for use as a primary dose and booster?

Dr Goodman: Sure. The mRNA vaccines, Moderna and Pfizer, the original strain vaccines were originally authorized for being used. They are now authorized really across the age groups, whereas the AstraZeneca vaccine has been authorized as a primary vaccination and is used more in adults. The same with the Janssen vaccine in adults. This is because the vaccine-induced thrombocytopenic thrombosis syndrome was seen more in younger age groups and therefore it's not really been rolled out for children. It's used in adults, those vaccines. Then recently we have the Novavax vaccine, which has been authorized in older children and in adults for the primary vaccination. Similarly, the Valneva vaccine for primary vaccination, which is less available, at least in the UK, but can be used now for vaccination as well. Again, this availability of different vaccines for different circumstances and different people needing vaccination is really important.

The booster vaccines have also now been authorized as mRNA vaccines. This is where the bivalent vaccines have really come into their own. That we now have an omicron combined with ancestral strain vaccine, which can be given to people over the age of 12. That's now being rolled out. In the UK, we follow something called the JCVI, which are our committee who give the advice in terms of what groups should be vaccinated and with what timings. We're vaccinating children and young people. We are advising that all of those over 12 can receive the 2 doses of Pfizer, the wild type. This was extended to a 12-week interval because of this issue of the myocarditis. But where somebody's at risk, such as those who have contact with immunosuppressed patients, they were offered these 2 doses at a smaller interval of 8 weeks rather than the 12 weeks.

Then the children who are in the age groups of 5 to 11 have been offered a lower dose, pediatric dose Pfizer vaccine at an 8-week interval. This is for those who are in at-risk groups and in contact with immunosuppressed individuals. Again, these people get a third dose. Rather than a booster, but a third dose in their primary schedule where they have severe immunosuppression so that you expect they won't have responded to the first and second dose and there's reasonable evidence that a third dose in that scenario can then help with the primary regime. That's the rationale for that. As I say, the 12-week interval to as a precaution, measure in terms of the myocarditis.

Then we offered, in the UK, booster vaccinations and then now autumn boosters for 2022 to those living in residential care homes, to older adults, to those working on the frontline, for example, to people over the age of 50 because we know that those people are at higher risk of COVID-19, and those with other underlying conditions that are over the age of 16 that have a higher risk. Carers, of course, for those who are more vulnerable because a carer is at risk of passing it on. Although, we've talked a lot about how these vaccines work and we haven't really talked about needing other vaccines, we also, it would be helpful to have other vaccines that are even better than the current vaccines at the reduction in transmission. We give vaccines to household contacts for this reason because there is some impact on the transmission, but really the vaccines were developed to reduce severe illness and hospital admissions and deaths.

The JCVI has also advised that adults are offered a single dose of the booster vaccines in the autumn booster program where people are having these boosters that they receive the bivalent vaccines, a single dose and that children also get the wild type. The children, however, get the wild type currently. Of course, that may change with licensing. We've newly got the Novavax vaccine available, but we use that in the UK when there's no other clinically suitable approved vaccine for that person.

We did a trial in the UK called the COV-Boost trial of fourth-dose boosters. In this trial, participants who had already had a Pfizer booster were randomized to have either a further dose of Pfizer or a half-dose Moderna. This was given approximately 6.5 months after their third dose. As you can see, there were these good responses in terms of antibody responses and cellular responses in these groups. In the COV-Boost trial, we found that the antibodies after the fourth dose were higher than we'd observed after the third dose, as you can see on these graphs to the right of this slide.

Dr Lacombe: Okay, great. That was really comprehensive, Anna. Thank you. Let's now switch topics and briefly touch on how to communicate with our patients. What are the common questions among patient regarding COVID-19 vaccines? I'd like to turn to Jörg to discuss a few of those questions.

Dr Schelling: Well, thank you Karine for asking me this question. Being in the practice almost on a daily basis, a lot of questions come up. The first question the patients always ask is, do I really need another booster? Some patients already got their second booster in February, March or even in April of 2022. Now they're asking whether they need a fifth one. This is always an interesting question. Others only have 3 and then they're talking about the fourth one. Others have family members they have to take care of. Others have new medical conditions that they didn't know about before. Others are undergoing chemotherapy now or radiochemotherapy because of a malignant disease. Others are immunocompromised now because they started getting antibodies because of a rheumatic disease or anything else. The question whether they need a booster or not is the question that is asked most frequently.

There was also a letter sent by the German health minister to everybody above the age of 60 that they should get their booster, but patients already had 4 shots and are otherwise perfectly healthy, except being over 60, also came with this letter asking whether they need a fifth shot now because the health ministry wrote them. People look at the media, people talk to the families, and in the end, sometimes they want to know the opinion of a professional telling them whether they need the booster or not. You have to put in all the things you know about the patient, his prior vaccinations, the number of infections he had with COVID before, the durations since the last vaccination. Immunocompromised patients, of course, have to be considered specifically. But in the end, there's always only a yes or no question. The patient looks you in the eye, you look deep into their eyes and then you say, "I would vaccinate you if I were you or if you were my brother or mother or whoever." It always ends up in a yes or no answer. This is the first question, which is always asked.

The second question, which is very important is if I need a booster and are the vaccines working as well because people know about the changing of the variants. They know that there has been Delta and most of them have been vaccinated during Delta or even during the first Omicron wave. Now they want to know whether the vaccines are working. Do they get the old vaccine? Do they get the newest one, the one with a BA.4, BA.5 combination? Of course, they are interested in that whether it's working right now and if it's going to work for the next couple of months at least.

The third one that is asked quite a lot is: are the boosters using the same ingredients, using the same amount or is it the same technology or do we have to switch to another vaccine as well? This discussion is starting to come up now because patients are also interested in whether they are always getting the same vaccine for long time or if there has to be a switch at a certain point. But with only the mRNA vaccines on the market and available for boostering, this question is also answered in always very simple just by saying they contain the same ingredients basically, but just different types of the virus, of the spike variant.

Those are the three question I'm asked most often in the practice. It's not a lot of discussion and not a lot of anxiety there. There's a lot of trust in many of the patients. If you stay authentic, also as a doctor, then usually you can help the patient answering these questions very fast and very successfully.

Dr Lacombe: There is also another question that is very frequently asked that if there are different situations that calls for different vaccine platforms. I don't know your opinion about that, Anna.

Dr Goodman: I was interested just on Jörg's comment about being authentic as a doctor. One thing that's nice about this situation as a doctor is that we've all also received the vaccine. We have this personal experience we can give to a discussion as well. Of course, we've talked to our own families. We obviously get all these questions about different situations. Is my personal situation different?

Now in the UK, at least, we have very clear guidance as to what vaccines you receive. There isn't choice as such. If you are in a particular group, you receive a particular vaccine. The group is really based on the risk of any adverse events in your group. If you are known to have anaphylaxis to an ingredient, if you're known to be allergic to part of a vaccine, of course we're going to find you a different vaccine to which you're not allergic. In my hospital, for example, we have an allergy clinic that then can guide people to make sure they have the correct vaccine, but actually our guidance is quite clear on this as well.

Different countries and different healthcare settings is based on really the cold chain and the availability. Different countries will use different vaccines really based on what they have available.

In terms of subpopulations, the vaccines, there doesn't seem to be that different age groups or different subpopulations, at least from what we have available, they seem to be effective fortunately across subpopulations and across age groups. At the beginning, there were a lot of questions from my friends and from family and from patients saying, "Well, if I have an autoimmune disease should I have a different vaccine to someone who doesn't have that or some of the risk factors for the vaccine-induced thrombocytopenic thrombosis," but actually that hasn't really been, VITT has turned out to be a phenomenon that's quite specific and hasn't been based on a lot of the things we thought might be risk factors.

Only in very, very specific subpopulations, such as when Jörg talks about Guillain-Barre syndrome happening, if it happens after vaccination with AstraZeneca, then you might consider giving a different vaccine for the next dose.

Dr Lacombe: That was really interesting. I think that it's time now to wrap up with a few concluding remarks. If I can just summarize a few points, as you have highlighted it, Anna, we need different vaccines because we have millions of people to get vaccinated. We definitely need a broad range of vaccines. We have seen that the efficacy far outweighs the risk associated with vaccination and usually adverse events are very mild. There are a few rare adverse events that might be serious. We have to be aware of that and to address them very specifically. Like the flu vaccines, we have to expect to get vaccines adapted each year to variants. It has been quite nicely highlighted during this talk. The trial with the BA.1 Booster is very reassuring regarding efficacy and safety. We are waiting for the data from clinical trials with BA.4 and 5. We have seen that vaccine equity is a very big issue. There is also a range of vaccines for primary vaccination according to authorization in your own countries.

I would like to thank you all for participating to this activity and please continue on to answer the questions that follow and complete the evaluation form. I want to again take some time to thank Anna and Jörg for this very comprehensive overview of vaccines to prevent COVID-19. Thank you very much. See you soon.

This transcript has not been copyedited.