Training the Immune System

The coronavirus has shown how important vaccines are for keeping the body’s defenses in shape to combat dangerous infections. The experts at Wacker Biotech have 20 years of experience producing vaccines based on microbial systems.

Vaccines do this by playing a trick on the body, leading it to believe it has been infected with a pathogen. The trick works by selectively exposing the body to either all or part of a killed or weakened organism. Not enough to cause disease, but enough to put the immune system on high alert. which reacts by forming antibodies to fight the virus or disease-causing bacterium – an immune response, in other words. This is also when memory cells are formed, allowing the body to remember the pathogen, even once the acute danger has passed. If the individual is infected again at a later point in time, the immune system will be prepared for it.

Researchers are now working round-the-clock on a vaccine for the SARS-CoV-2 virus, which can trigger the respiratory illness COVID-19. The disease was first detected in December 2019 in Wuhan, a city home to millions of people in the Hubei province of China. In January 2020, the illness developed into an epidemic in China, ultimately spreading around the world to become a pandemic. Because the SARS-CoV-2 coronavirus had been unknown up to that point, it is often referred to as the “novel” coronavirus. According to the World Health Organization, 100 projects aimed at the development of a vaccine are currently underway (as of May 2020).

Several research institutes are also looking to this new class of vaccines to combat the SARS-CoV-2 virus. According to the journal Nature, 20 projects throughout the world are currently underway with the aim of bringing an RNA- or DNA-based vaccine for the novel coronavirus to the market. Twenty-five projects for developing viral vectors have been launched as well (as of April 2020). Current efforts to combat the coronavirus pandemic could pave the way for these new classes of vaccine.

“The rapid spread of severe infections like SARS, Ebola, and now the SARS-CoV-2 virus once again underscores the need for developing new vaccine technologies so that we can respond to novel viruses more quickly and effectively,” says Cronet. Wacker Biotech will also be looking into research on nucleic-acid-based vaccines.

As a CDMO (contract and development manufacturing organization), Wacker Biotech works behind the scenes. “We develop production processes and produce vaccines for our pharmaceutical industry customers, but we don’t do the corresponding concept development or marketing ourselves,” Cronet explains. What Wacker Biotech experts do contribute are over 20 years of experience developing and producing living microorganisms, proteins and polysaccharides. These active substances are then used both in (pre)clinical studies and in commercial products.

Wacker Biotech produces vaccines at three sites: one each in Jena and Halle, Germany (Wacker Biotech GmbH), and one in Amsterdam (Wacker Biotech B.V.). Wacker Biotech GmbH and Wacker Biotech B.V. are both wholly owned subsidiaries of Wacker Chemie AG.

“The concept behind a vaccine is simple,” Cronet observes. “Developing and manufacturing one is anything but simple.” It can take ten to twelve years on average to move from the research phase to approval. In the case of a vaccine for SARS-CoV-2, however, scientists are hoping that an accelerated process could bring us to that goal within 12 to 18 months. The only reason this could work is because most vaccine candidates draw upon highly efficient development and clinical testing platforms that were devised for other pathogens. Researchers have already re-engineered existing vaccines by swapping out their genetic sequences so that they will respond to SARS-CoV-2.

From preclinical to clinical development, from vaccine manufacturing to market delivery: Wacker Biotech supports its customers the entire way. An individual production process is developed for each vaccine (candidate) and adapted to the stage of development that a given vaccine has reached. “Depending on the vaccine, that takes ten to fifteen months,” says Cronet. Once the process is in place, millions of doses of vaccine can be produced within one to two weeks.

Wacker Biotech has already manufactured vaccines for a wide range of infectious diseases, such as cholera, meningitis A and C, and Haemophilus influenzae type B (Hib). “At this point we’ve provided over 650 vaccine batches for clinical and commercial applications,” Cronet notes. Whereas vaccine manufacturing at Jena and Halle focuses on protein-based agents produced through the use of the bacterium Escherichia coli, the Amsterdam site makes attenuated live vaccines, polysaccharide vaccines and conjugate vaccines, too. This involves the use of an array of additional microorganisms, such as Corynebacterium diphtheriae, Salmonella typhi or Vibrio cholerae.

Production in this case proceeds in multiple steps, and these vary depending on the type of vaccine. The first step takes place in the laboratory, where what are known as precultures are prepared of the vaccine candidate that the customer has provided. This is followed by scaling up production in single-use reactors or in stainless steel tanks called fermenters. Here the bacteria produce the target active substance – in the case of a conjugate vaccine, they build the desired polysaccharides (see illustration). The polysaccarides next undergo multiple purification steps and lyophilization, after which they are chemically activated and, in the final step, bound to the carrier protein to form the finished conjugate vaccine.

Wacker Biotech sites carry out this process in facilities meeting biosafety levels of 1 (Halle and Jena) and 2 (Amsterdam), on a scale of 1 to 4. The sites produce vaccines in stainless steel tanks with capacities ranging from 270 to 1500 liters, as well as in a 250-liter single-use reactor. This allows the company to adapt production volumes as needed – small quantities of vaccine for clinical trials, larger amounts for supplying the market later on. In Amsterdam, active substances can also be dispensed into as many as 20,000 vials per batch following production. Freeze-drying (lyophilization) at the end of the production process is an option as well. “All of our facilities meet the highest standards of quality. They’ve been approved by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMA), which means we can supply the global market,” says Cronet. Wacker Biotech ships its vaccines all over world.

Capacity utilization rates at all three Wacker Biotech sites are currently good, in part because the vaccine market is constantly growing – and not just because of the search for a SARS-CoV-2 vaccine. Scientists are continually discovering new pathogens, including many for which no vaccine currently exists. Also, because some pathogens possess the ability to adapt to their environments, there is a constant need for new vaccines to combat mutated organisms – this is why new flu vaccines are developed every year. Put in terms of actual numbers, the vaccine market is growing at an average rate of seven percent a year. Studies have indicated that this is not likely to change in the coming years. Keeping pathogens in check remains a never-ending task – and that goes for Wacker Biotech too.