The mRNA vaccines are currently considered the gold standard among Corona vaccines. Since the beginning of the year, a protein vaccine has been in use, which some people who were sceptical about mRNA technology have been waiting for. How does it work, and how should it be viewed in terms of its effectiveness?
Protein vaccines belong to the classic types of vaccine, like those we are familiar with from flu vaccines, for example. The new protein vaccine Nuvaxovid contains the spike protein of SARS-CoV-2 and an additional immune modulator promoting the activation of the immune response. The results of the clinical trials are quite promising: They show that vaccinated people are very well protected against developing a severe course of the disease. Unfortunately, the initial expectations of significantly increasing the vaccination rate with a traditional vaccine have not been fulfilled. This may be due, among other things, to the fact that this vaccine has not yet been adapted to the currently circulating Omicron variant. However, much like its mRNA counterparts, this vaccine does not protect against infection. Only time will tell whether or not the immune response will last over an extended period of time.
Do we already know more about this for the mRNA vaccines?
What we do know about the efficacy of mRNA vaccines is that they provide good protection against severe disease for about three to six months. After that, they should receive a booster. This is the case because these vaccines primarily address the so-called humoral immune response. This is the part of our immune system that is responsible for rapid production of precision-fit antibodies. Although, of course, this is enormously important in the fight against a pathogen, it sadly is not enough to build up long-term immunity. This requires the activation of the so-called cellular immune response: Memory cells that remember unwelcome invaders even years after an infection and can quickly produce antibodies when they re-encounter the same pathogen. This immunological memory seems to be only weakly activated by the mRNA vaccines. We do not yet understand why this is the case. But let me stress the following: The Corona vaccines developed so far were primarily intended to protect against severe disease. And they do – they have achieved their original goal.
With its new mutations, doesn't the virus also outrun the effectiveness of the vaccination?
Yes, unfortunately this is true. The vaccines available today are based on the spike protein of the original virus strain from 2019. And both, the Delta variant and the new Omicron variants, include a considerable number of mutations in the spike protein. This causes the antibodies produced in the course of a vaccination to no longer fit optimally. It was a surprise to scientists that SARS-CoV-2 was able to change so quickly because the coronaviruses we know from harmless colds do not do this to the same extent. I don‘t like to compare Corona and influenza, but the challenge of having to adapt vaccines on a regular basis because the pathogen changes so quickly now seems to be evident with SARS-CoV-2 as well. Currently, clinical trials on both mRNA and protein vaccines adapted to the Omicron variant are underway. The first mRNA vaccines have just been approved by the European Medicines Agency (EMA) and are now being used for booster vaccinations.
Recently, Valneva's vaccine was approved as the first whole-virus vaccine against SARS-CoV-2. What are its features?
Valneva's vaccine VLA2001 is an inactivated whole virus vaccine, also called a dead vaccine. The core of the vaccine is a complete, inactivated SARS-CoV-2 virus, which should trigger a broader immune response due to its multiple attack surfaces. The supplementary addition of immune stimulants, known as adjuvants, also gives hope for a stronger and longer-lasting immune response. However, Valneva has also developed its dead vaccine on the basis of the original Corona variant. By confronting the immune system not only with the spike protein but also with all other viral components, the virus has a much harder time evading the immune response.
Are there any other promising candidate vaccines currently under development?
As far as the development of second generation Corona vaccines is concerned, there are two different main approaches. On the one hand, research focuses on the development of vaccines that contain different variants of the spike protein. On the other hand, there are promising approaches to include other viral components in the vaccine formulation besides the spike protein. Initial results show that vaccines containing more than one variant of the spike protein may also provide better protection against other variants, even if they are not included in the vaccine. Another interesting approach is the development of mucosal vaccines that can be administered through the nose, for example. Here, the hope is not only to protect against severe disease, but also to prevent the transmission of infection. However, this research is still relatively in its infancy and needs time before approval.
SARS-CoV-2 has taken the research labs virtually by storm in the past two years – has it found a place in your research as well?
Yes, of course. We aim to understand why the immune response after vaccination is better in some people than in others. As part of this work, we are also looking for differences between different vaccines and vaccine combinations after the first, second or third vaccination. We are particularly interested in the immune mechanisms in humans that might explain why the vaccine response can vary so strongly. We have been investigating this for some time using the influenza vaccine as an example and are now including Corona in our studies. In addition, we are doing research on the development of next-generation Corona vaccines. In this context, we are focusing primarily on vaccinations via the mucous membranes – for example as a spray acting on the nasal mucosa – aiming to perhaps get a future vaccine that protects against infection as well.
In your view, has the Corona pandemic been a booster for vaccine research?
Oh yes, I would fully support that. But that is also the only good thing to emerge from the pandemic. The sudden appearance of a previously unknown and dangerous pathogen has shown: We need forward-looking research. We can't just start when the pandemic is in full swing already. In order to be able to counteract pathogens, basic research in the literal sense is fundamental. The more we know about viruses, bacteria and how our immune system works, the faster and more efficiently we can produce vaccines. Of course, another important component is good interdisciplinary and international cooperation. And this has indeed been evident during the past two years of the pandemic: The scientific community has moved closer together and is exchanging ideas better than ever before.
Interview: Nicole Silbermann
Published: October 2022
