The world-leading region on virology? Is based in the greater Rotterdam – The Hague area

Antibody against corona discovered in Rotterdam

The Rotterdam company Harbor Antibodies may have discovered an antibody against the COVID-19 virus. A world first. Research leaders Frank Grosveld (Erasmus MC) and Berend Jan Bosch (Utrecht University) developed the antibody for previous variants of the SARS virus. Their publication is currently being approved by the leading journal Nature. For their antibody, the consortium is now trying to get a pharmaceutical company on board that can produce the antibody on a large scale.

Janssen is making rapid progress with corona vaccine

The best known among the biotech companies in the greater Rotterdam -The Hague area is Janssen, with a large vaccine production plant at the Leiden Bio Science Park. Janssen was responsible for discovering the Ebola vaccine and will probably also be the first to market an HIV vaccine. The two largest core activities – Janssen Biologics and Janssen Vaccines – together account for the third largest R&D expenditure in the Netherlands, after ASML, Philips and KPN.

Janssen is currently making significant progress in developing a corona vaccine and expects to have a vaccine available for emergency situations by January 2021. The progress is so promising that Janssens mother company Johnson & Johnson and the United States Department of Health pushed 1 billion dollars into the development and production facilities for the vaccine.

“The world is facing an urgent public health crisis and we are committed to doing our part to make a Covid-19 vaccine available and affordable globally as quickly as possible,” Johnson & Johnson CEO Alex Gorsky said in the statement. “Johnson & Johnson is well positioned through our combination of scientific expertise, operational scale and financial strength to bring our resources in collaboration with others to accelerate the fight against this pandemic.”

Out of twelve “vaccine constructs” that have been tested for effectiveness on animals, the most promising candidate has been selected, along with two back-up candidates. The vaccine is a so-called “vector vaccine” (see below) and is based on the Ebola vaccine that Janssen previously produced. This enables Janssen to accellerate the vaccine development because the construct is already proven safe. Clinical trials are expected to start in September. Janssen is currently setting up the vaccine production plant on Archimedesweg in Leiden in such a way that the vaccine can also be produced there, Dutch newspaper Financieel Dagblad reports. The aim is to produce about a billion vaccines per year.

But Viroclinics, Halix, Batavia Biosciences, Harbor Antibodies are located in this region as well. All of them world class as well. While Janssen and ViroClinics are also engaged in research into viruses and vaccines, companies such as Halix and Batavia Biosciences are mainly involved in production and the process.

Leiden Bio Science Park

When we speak to ViroClinics on the phone, it sounds resolutely: “Greater Rotterdam – The Hague is absolutely world leader in virology, in particular Erasmus MC. It really takes years of research and they publish in high impact papers such as Science and Nature. ” But if we want to ask further, CEO Bob van Gemen really has to hang up. “It’s crazy over here. Can we have this call in a few weeks? ”

It is also busy at Batavia Biosciences. “But we have it under control,” says virologist and CEO Dr. Menzo Havenga. He likes to take us along in the how and what of vaccine development.

How does a virus work?

“A virus is capable of high-jacking your cells,” explains Menzo Havenga. “Many viruses actually only do two things, (1) infect / invade your cells and (2) multiply within those cells. When a virus enters the human cell, it can force the cell to do only one thing: multiply the virus. And that goes fast: one virus particle in the cell can lead to no less than 100,000 virus particles 24 hours later. After that, the human cell often dies. ”

“What makes this coronavirus so dangerous is that people can already infect each other before they start having any symptoms. The amount of virus that is secreted is much smaller at this stage but increases along with the amount of symptoms. But that intermediate phase complicates the control over the spreading of the virus; it can easily pass from person to person without us being aware of it. The ever growing world population acts as a catalyst. In 1950 there were only 2.5 billion people on Earth, now there are 7 billion. We fly to the other side of the globe several times a year. And the virus travels with us just as fast. ”

How does a vaccine work?

“With protection against a virus, you help the body to fight the virus as good as possible. If people are already sick, you do this with the regular administration of antibodies. You give, as it were, an extra dose on top of the antibodies that the body already produces. This reduces the amount of virus and dampens the symptoms of the disease. Antibodies have a temporary effect and you must therefore continue to administer them until the immune system takes over. ”

Preferably you want to protect people for a longer period, so that they cannot get sick when contamination occurs; then one speaks of a vaccine. You give the body a taste of the virus, so that contact with the real virus no longer results in illness. You have roughly three methods:

• Whole-killed virus vaccines – you grow the virus and then inactivate it using heat, chemicals or radiation. You inject that inactivated and therefore harmless virus into humans to elicit an immune response.
• Life-attenuated virus vaccines – an attenuated variant of the virus, which is developed in the lab by growing it continuously, or by removing certain parts of the genetic code. That attenuated virus is raised and purified and you bring it into humans to trigger an immune response.

“It is difficult with the above classic methods: they require that you cultivate the virus in large quantities. But with dangerous viruses, such as Ebola, Marburg, Niphah or this corona virus, you prefer not to do so because of the risk of infection. The risk of working with such viruses in such quantities is far too great. That is why a third method has also been developed:

• Vector vaccines – A small piece of DNA from the dangerous virus is introduced into the DNA of a relatively harmless virus, such as the adeno or measles virus. This harmless virus is cultivated and purified. When injecting this vaccine into humans, the harmless virus (the vector) will bring the DNA of the dangerous virus into the human cell. There, humans develop an immune response to the dangerous virus.

The piece of DNA from the dangerous virus used in a vector vaccine is almost always the so-called SPIKE protein. Menzo Havenga explains that the body often responds the most strongly to the SPIKE protein, because this virus protein allows the virus to enter the human cell. With the corona virus, these are the bulges you see in photos. In a natural immune response, antibodies are also made against the SPIKE protein. They block binding to human cell receptors.

Getting a vaccine to the market

Once you have found a vaccine, you will quickly get featured in the newspaper. But you are not there yet. You need to find out the correct dose and test whether unwanted side effects occur. Also, large-scale production is no easy task, it requires monitoring. Does the virus remain stable during upscaling? Will the vaccine continue to do what it is supposed to do on a larger scale? Once you manage to produce the vaccine on a sufficient scale, you will begin clinical studies in humans.

In the clinical trials, safety and efficacy are tested:

• Stage 1 (dozens of patients) – Is the vaccine safe? Does it produce unwanted side effects?
• Stage 2 (hundreds of patients) – Is the drug effective? Does it work?
• Stage 3 (thousands of patients) – How effective and safe is the vaccine in a large population?

Before a produced vaccine can be tested in humans, you first need approval from the European Medicines Agency (EMA) and the US FDA. All in all, marketing a vaccine takes at least 5 to 10 years. However, people are looking for faster ways. In the case of Janssen’s corona vaccine, for example, safety was already largely determined when Janssen used vector technology for the Ebola vaccine at the time. As a result, certain steps can now be skipped or accelerated.

Future of vaccines: faster production, easier administration

Looking to the future, Menzo Havenga sees a number of opportunities for the future of vaccines. He expects existing vaccines to be produced much more efficiently and therefore cheaper.

“At Batavia, for example, we are working on producing much larger quantities of virus on a smaller surface area, which reduces costs.” One of the other promises lies with vector vaccines. “If we can establish a stable base of one, two or three vectors as a platform, we can bring vaccines to market much faster. It makes little difference to the production process whether you put pieces of the Ebola, Lassa or COVID-19 virus in it. ” What takes a lot of time are the required safety studies. Here Janssen has an advantage; it can accelerate its vaccine development, because their vector had already been proven safe in the research for the Ebola vaccine. ”

Finally, Havenga also sees a lot of innovation in the application method of vaccines. This can now be done with plasters or new small needles, for example. “Then you need much less vaccine than with classic administration. This method may sound like an afterthought, but it is essential in the case of a virus outbreak on the African continent, for example. Most countries there have too little storage capacity to store all those ampoules refrigerated. The existing refrigerators are already full of other routine vaccines there. In the event of an outbreak, there is no room for a new vaccine. If you have to send millions of vaccines there in boxes of 3x3x3 cm. That really doesn’t fit. Such a plaster offers a solution for those kinds of practical problems. ”