Expert: We need other vaccines

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The licensed Corona vaccines were developed to prevent severe disease progression. But they are less effective at protecting those vaccinated from infection and thus from virus transmission. A new type of vaccine could close this gap.

The further the vaccination campaign progresses, the more frequently so-called breakthrough infections occur: even those who have been vaccinated twice become infected with the coronavirus. The Robert Koch Institute (RKI) lists a total of 8,715 vaccine breakthroughs since February 2021 (as of Aug. 5, 2021). Since many infections are asymptomatic, a higher number of unreported cases can be assumed.

What is clear is that even those who have been vaccinated can become infected and continue to carry the virus. This makes it even more difficult to break the chain of infection, especially among the much more infectious delta variant. Do we need a new type of vaccine that not only prevents severe courses of disease, but also prevents infection with the coronavirus?

Nasal sprays as a solution?

Dr. Ulrich Lauer and his team at the University Hospital of Tübingen are researching this new generation of vaccine – a nasal spray. Since the beginning of the pandemic, this type of mucosal vaccine has been considered a great source of hope, because it could prevent even those who have been vaccinated from becoming infected.

In the NDR podcast “Coronavirus Update,” the head of virology at the Charité hospital in Berlin, Christian Drosten, explained in October 2020: “That’s what we would like to see, that we have vaccines that also protect the mucous membranes. That stimulate the special immune system there, so that at some point, if someone inhales a whole load of virus into the nose, they are no longer infected, so they don’t even get a mild course, but no course at all. The virus is immediately slowed down in the nose.”

However, of the 100 Corona vaccines currently being tested in clinical trials, only eight are so-called intranasal vaccines. In the spring, Oxford University announced it was now testing the Astrazeneca vaccine developed there as a nasal spray. Lauer’s team is also researching a nasal vaccine. He explained the active ingredient and the state of research to t-online.

Ulrich Lauer: At present, we only have first-generation vaccines. These were developed under the premise of being able to be approved as quickly as possible and, accordingly, initially had “only” to fulfill the requirement of protecting against severe courses of disease and death in connection with a covid 19 disease. As a rule, they achieve this goal very well, because even people who become infected despite being fully vaccinated generally do not become seriously ill and only very rarely die. What we need now, however, are vaccines of a new generation that can also efficiently slow down the infections that are currently still caused by double vaccination.

How can this be achieved?

SARS-CoV-2 is a respiratory virus, i.e. a pathogen that is transmitted via the respiratory tract. Accordingly, in the future it will be necessary to start vaccination in the respiratory tract, where the virus finds its way into the body, in order to block it as early as possible.

You are researching vaccination via nasal spray …

Yes, because our respiratory tract is the decisive gateway for the virus. It is precisely here that we need the very first, strongest possible protective barrier.

But does the body react differently to a vaccination through the nose than to an injection into the upper arm?

Indeed, in the case of vaccination into the upper arm muscle, which has been common up to now, the immune system primarily develops antibodies of the immunoglobulin G (IgG) subtype. With nasal vaccination, on the other hand, antibodies of the immunoglobulin A (IgA) subtype are also secreted into the respiratory tract, i.e. exactly where the coronavirus wants to enter our body. These IgA antibodies lurk in the airways after intranasal vaccination, already waiting for invaders. If SARS-CoV-2 virus particles then arrive, they are intercepted by the IgA antibodies already waiting and immediately neutralized, so that infections can generally no longer even begin.

And how exactly does vaccination via the nose work?

In our second-generation vaccine, we are also designing a carrier virus (as in Astrazeneca’s vector vaccine), i.e. a virus that is harmless to humans, through which parts of the genetic material of the coronavirus are transported into our bodies and trigger a strong immune response against SARS-CoV-2. Together with researchers from the Max Planck Institute of Biochemistry in Munich, we are working with a specially genetically modified Sendai virus that can no longer replicate in the body and is therefore particularly safe. This will then make vaccinations possible, especially for people with a pronounced immune deficiency.

And these carrier viruses transport selected parts of the genetic material of the coronavirus into the body?

Exactly: The spike protein of SARS-CoV-2 is the key to the cell. Thus, the virus enters the cells with it. The IgA antibodies produced after intranasal vaccination dock precisely onto the spike protein of the coronaviruses and thus prevent their penetration, nipping any infections in the bud.

Does this mean that infections can be completely prevented in the future?

Yes, because coronaviruses would then be eliminated as soon as they enter the body via the respiratory tract and would therefore no longer have any chance of roaming around in our bodies and severely damaging organs such as the lungs, heart, liver and kidneys. This could close the weak point of previous vaccines and for the first time create “sterile” immunity. In other words, all coronaviruses would be completely eliminated at the outset. This could bring us much closer to the goal of herd immunity.

How far along are you in your research?

The first prototypes for this new type of vaccination have already been produced. We expect to be able to conduct the first clinical trials next year. We are benefiting from the fact that the principle of intranasal vaccination is already known from the fight against influenza. Nasal vaccinations are already approved for children.

Of course, nasal vaccination would simplify many things.

Yes, the application is of course much less complicated, almost like a hay fever spray that everyone knows. Serial vaccinations could take place much more easily and much more quickly. Especially in developing countries, this would simplify logistics enormously.

Would a single dose then be enough for complete and lasting immunization?

That is not yet clear, although it will certainly also be a question of dosage. Of course, this still has to be precisely determined in clinical trials. But I can also imagine, for example, using nasal vaccination as a booster after an initial intramuscular vaccination. Data show that these heterologous vaccines can increase efficacy even further. And, of course, one would then also continuously adapt these vaccines to the ever emerging variants.

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