130 years of vaccine
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Leading-edge research from Switzerland: Janssen Vaccines of Bern

 

130 years ago, as well as today, innovative vaccines are being developed at Bern. At its time it was the «Swiss Serum and Vaccine Institute» (SSII), now the company is part of Janssen, the pharmaceutical company of Johnson & Johnson.

Work on Ebola vaccine: laboratory work at Janssen Vaccines in Bern.

Janssen Vaccines of Bern: seen from the skies, the company's site is a colourful patchwork ensemble. Office blocks dating from the 1950s rub shoulders with warehouses and modern industrial buildings, interspersed with extensive stretches of open grass. The architecture mirrors the rich diversity of this firm's history, based now – as in the past – on the manufacture of innovative vaccines. As its specialities, the company focuses on viral and bacterial vaccines for clinical development phases. This means that the experts in Bern collaborate closely with their colleagues at Janssen Vaccines in the Netherlands on research, experimentation and testing so that new products can be made available. Large-scale production of vaccines takes place later on, at other locations in the network of allied companies. Probably the best-known result of the collaboration between the laboratories of these two sister companies is the vaccine against Ebola, which received approval by the European Medicines Agency’s (EMA) on 1 July 2020. And since January 2020, before lockdown threw the world into a state of shock-induced paralysis, much activity in Bern has revolved around the development of another new vaccine: the one against COVID-19.

Filled in Vials

 

This presented a challenge for the 300 employees from 22 different nations who work at the Bern site – and they have tackled it with great commitment and enthusiasm. Together with their colleagues in Leiden (Netherlands) and the USA, the team of biologists, biochemists, virologists, pharmacists, process engineers, medics, technicians, laboratory staff and many more are spearheading J&J's research and development work to produce a COVID-19 vaccine candidate. As on many occasions in the past, the division of tasks between the sister companies has proven to be a key advantage for rapid progress in this project: once the genetic engineering research is completed in the Leiden laboratories, the basic ingredient can be manufactured simultaneously in Leiden and Bern – so capacity is increased. The processed vaccine will then be filled into vials in Bern under absolutely sterile clean room conditions. The sterile production facility for clinical test material at Bern plays a key part in the flexible and independent working style that is a hallmark of the Janssen conglomerate.

«There is work to be done; the patients are waiting!»

Paul Janssen (1926 – 2003), Belgian physician and company founder.

Since January, Janssen has focused enormous energy on developing a COVID-19 vaccine. Nevertheless, work is still continuing on projects that were already under way: one example is a vaccine against a relevant selection of E. coli bacterial strains that are showing increasing resistance to antibiotics. Resistant intestinal bacteria such as these can often cause serious post-surgical infections that are difficult or impossible to treat with antibiotics. In 2018, more than 20% of E. coli infections in Switzerland showed multidrug resistance and more than 25000 people have died last year in EU countries as a result of a severe infection caused by multidrug-resistant E. coli. Claudio Thomasin, Scentific Director at Janssen Vaccines Bern, feels a special commitment to this project. He explains why: «The aim would be to administer the ExPEC (Extraintestinal Pathogenic Escherichia coli) vaccine, if approved by the authorities, as a preventive measure, especially to elderly patients at risk. We believe that it could help to significantly reduce severe cases of urogenital infections or bacterial sepsis, and this would make it possible to save lives.»

KEY ROLE IN CANCER THERAPY

 

In the field of oncology too, the Bern researchers are making successful progress with genetically optimised viruses. There have already been major advances in the production of lentiviral vectors (LVV), which play a key part in modern leukaemia therapy. Like the adenoviruses that are deployed against Ebola and in the COVID-19 vaccine, these lentiviruses can be used as «gene taxis». They function in combination with isolated immune cells – known as the T-cells in leukaemia patients. The T-cells are modified by the lentiviral vector so they can ultimately recognise the cancer cells and destroy them in a targeted attack. And nowadays, this highly promising approach in medical therapy is even making it possible to cure certain types of leukaemia – so CAR-T (chimeric antigen receptor) therapy is a real life-saver. According to Claudio Thomasin, this vaccine is opening up entirely new prospects for treatment: «This novel therapeutic approach benefits patients who have had little or no help from the standard therapeutics available until now.»

 

The facilities in Leiden and Bern are also working jointly on other projects, including the development of new viral vaccines against HIV, Zika and RSV (respiratory syncytial virus). Not least, these advances have come about because Dr. Paul Janssen (1926–2003), the founder of Janssen Pharmaceuticals and Paul Stoffels, M.D. (Chief Scientific Officer; Vice Chairman Executive Board) already realised the importance of vaccines as a crucial instrument to combat infectious diseases back in the 1980s, when HIV emerged in Africa. Stoffels has been striving to produce an HIV vaccine for the last 30 years – there is still a long way to go, but the company has never been closer to this goal than now. One factor that has made this possible is the high-tech AdVac® technology that Janssen took over and continued to develop from 2011 onwards following its acquisition of Crucell, the Dutch start-up and its sites in Leiden and Bern.

Recent years have seen tremendous advances in research and development at the Bern site, in tandem with the partner companies in the Netherlands and the USA. Janssen Vaccines' Bern facility plays a vital strategic role in the group today. According to Dirk Redlich, Head Vaccine Process and Analytical Development at Janssen Vaccines: «It's the Swiss army knife of our vaccine division.» And that applies not only to research and development work on new vaccines, but also to commercial production of the Ebola vaccine which received approval by the European Medicines Agency’s (EMA) on 1st July 2020, and to the manufacture of lentiviral vectors. The company's management is proud of its track record to date. To quote Dirk Redlich, these achievements show «that the investments and the long years of planning, platform development and process optimisation for innovative vaccines and other viral vectors have all paid off.» For the future, Redlich is aiming for a pipeline of vaccines to further build on the technology platform that has now been developed to market readiness.

It started with a smallpox vaccination

«Let me tell you my secret of success: all my strength is nothing but endurance.»

Louis Pasteur (1822 – 1895), French microbiologist and chemist.

«I wish that in war against the smallest but most dangerous enemies of mankind, one nation may overtake the other again and again.»

Robert Koch (1843 – 1910), German physician and microbiologist.

Trouvailles of the swiss serum and vaccination institute (SSII)

Johnson & Johnson had every reason to celebrate on 1st July 2020. Almost unnoticed by the general public, Janssen, the group's pharmaceutical company, had succeeded in creating a part of a two-dose vaccine regimen to help prevent another lethal Ebola epidemic.

 

GENERATIONS OF CHILDREN WERE VACCINATED

 

Janssen Vaccines of Bern can claim part of the credit for the development of this vaccine in a relatively short time after the last devastating outbreak of the epidemic in Africa during 2014. Originally a Swiss enterprise, Janssen Vaccines was acquired by Johnson & Johnson from Crucell, the Dutch biotech company, in 2011. It can look back on a success story spanning 130 years. For many decades, the company was known as the Swiss Serum and Vaccine Institute before it was renamed as Berna Biotech; thanks to vaccines from Bern, whole generations of Swiss children were immunised against mumps, measles and rubella, and almost the entire Swiss population was vaccinated against tetanus or influenza. The next chapters of the success story are already being written. Together with, Janssen Biologics Leiden, Netherlands, the Bern-based researchers are competing to develop a vaccine that will provide protection against COVID-19. The basis for their efforts is a technology platform that was already used to produce the ebola vaccine.

 

Vaccine research, development and distribution have comprised the company's core business from its very earliest days. The history of vaccine production in Switzerland has its beginnings back in the late 19th century. The year is 1883; throughout Europe, scientists are starting to understand the potential of vaccinations to combat infectious diseases. Louis Pasteur has already developed vaccines against fowl cholera and anthrax, while in Berlin Robert Koch is undertaking research into tuberculosis and cholera. Encouraged by the success of vaccinations that have already been performed against smallpox, Charles Haccius (1855 – 1933) of Lancy near Geneva establishes the «Institut Vaccinal Suisse», a vaccine production enterprise, in his home town – at the age of only 28! Almost immediately after launching the business, he already secures contracts with the Swiss cantons of Bern, Vaud, Aargau, Geneva, Neuchâtel, Fribourg, Thurgau, Valais and Solothurn that guarantee acceptance of his smallpox vaccine. It would later become known as «Lancy-Vaxina» and would remain in the product portfolio for almost 100 years. Lancy-Vaxina was used until recently in the worldwide vaccination campaigns against smallpox undertaken by the WHO from 1967 onwards, and it only became obsolete when the eradication of this infectious disease was declared in 1980.

1883: BIRTH OF THE «INSTITUT VACCINAL SUISSE»

 

Twelve years later in 1895, Prof. Dr. Ernst Tavel (1858 – 1912), a medic at the University of Bern, turned his attention to antitoxin serum therapy against diphtheria. This had only been developed shortly before, mainly by Emil von Behring (1854 – 1917). In the same year, Prof. Tavel collaborated with the entrepreneurs Albert Vogt (1858 – 1935) and Johann Friedrich Häfliger (1834 – 1911) in Bern to establish a company named «Haefliger & Cie., Kommanditgesellschaft zur Herstellung bakterio-therapeutischer Produkte» («Haefliger & Cie., Limited Partnership for the Manufacture of Bacterio-Therapeutic Products»). Haefliger & Cie. was the first company in Switzerland to manufacture the diphtheria antitoxin serum – the first effective therapy for this infectious disease, which is especially dangerous for children.

START-UP TIME FOR VACCINE MANUFACTURERS

 

Only three years later, in 1898, the two companies merged to form the Swiss Serum and Vaccine Institute (SSII) based in Bern. SSII registered the «Berna» wordmark in 1939 and the products were sold under this name from then on.

 

At first, the company continued to focus on its core competence: the production of smallpox vaccine and antitoxin serums against diseases such as diphtheria and tetanus. As time went on, the range was expanded to include vaccines against cholera, polio, typhus, meningitis and influenza among others, as well as various medications and products for diagnostics, dentistry and veterinary medicine.

Founders of the Swiss Serum and Vaccine Institute (SSII)

Dr. Johann Friedrich Häfliger

1834 – 1911

Dr. Albert Vogt

1874 – 1942

Prof. Ernst Tavel

1858 – 1912

A success story: Poliomeylitis vaccine from Berna, 1956.

THE FIRST ORAL POLIO VACCINATION

 

At first, the company continued to focus on its core competence: the production of smallpox vaccine and antitoxin serums against diseases such as diphtheria and tetanus. As time went on, the range was expanded to include vaccines against cholera, polio, typhus, meningitis and influenza among others, as well as various medications and products for diagnostics, dentistry and veterinary medicine.

 

By concentrating its efforts and building on scientific findings from international research and development, the company went on to manufacture new products: between 1951 and 1961, vaccines against tuberculosis and staphylococcus infections were developed along with a combined preparation to protect against diphtheria, tetanus, whooping cough and polio. The first oral vaccine against polio followed in 1961.

SPECTACULAR TYPHUS VACCINATION

 

In 1975, the SSII achieved spectacular fame well beyond Switzerland's borders with a new approach to typhus vaccination. This led to the development of Vivotif, the oral typhus vaccine that has been available on the market from 1980 until the present day. And Triviraten, a combined vaccination against measles, mumps and rubella, has helped generations of Swiss children to grow up in good health. Another milestone was chalked up in 1994 with Epaxal, a vaccine against hepatitis A. And since 1997, Inflexal V – a vaccine against seasonal influenza – has immunised many people in Switzerland against the flu.

 

THE DECODING OF GENETIC CODES

 

SSII was renamed as Berna Biotech in 2001. New scientific findings opened up new approaches to vaccines. Then in 2006, Berna was acquired by Crucell, the Dutch biotech company. In the years between this acquisition and the sale of the company to Janssen (the pharmaceutical arm of Johnson & Johnson), the Crucell scientists created the AdVac® genetic engineering platform to develop modern vaccines. Following the sale to Janssen, further development work on this platform continued and it was brought to maturity within the Janssen Group in collaboration with the biotechnology laboratories at Janssen Biologics in Leiden (Netherlands). Now, under the name of Janssen Vaccines AG, this company that has its roots in Switzerland is making history again – thanks not only to the vaccine against Ebola but also by working to achieve its declared goal of a vaccine against COVID-19 in the near future.

Vaccination: a revolutionary idea

«I am not surprised that people are not grateful to me; but I am surprised that they are not grateful to God for the good that he has made me an instrument»

Edward Jenner (1749 – 1823), English physicist and scientist

The existence of pathogens that cause diseases but are invisible to the human eye only became known in relatively recent times. It was not until the end of the 18th century that they were gradually tracked down. Two men were the key figures who launched the history of vaccination: Edward Jenner of the United Kingdom (1749 – 1823) and the Frenchman Louis Pasteur (1822 – 1895). They discovered that the body forms an immune defence on first contact with a pathogen, and from then on it can no longer fall ill.

 

INFECTED WITH COWPOX

 

In 1796, the country doctor Edward Jenner infected eight-year-old James Phipps with cowpox – and the boy then became immune against the far more dangerous «real» smallpox. However, Jenner's method worked empirically: there was still no theoretical explanation of where this «poison» that causes disease actually comes from. This knowledge was supplied 80 years later by the chemist Louis Pasteur. He discovered that micro-organisms are responsible for triggering diseases. In 1879, building on Jenner's knowledge, he developed the first vaccines against fowl cholera and anthrax with weakened pathogens. But it was only in 1885 that his successful public breakthrough came with the vaccination against rabies, the most lethal of all viral diseases.

Harper's Weekly illustration showing Louis Pasteur supervising an inoculation for hidrophobia, 1885.

Louis Pasteur with Joseph Meister, the first person to be inoculated against rabies in 1885.

In the 19th century, the successful results of these discoveries attracted dozens of ambitious doctors, biologists and chemists into laboratories where they devoted their efforts to vaccine research. First and foremost among them was the German doctor Robert Koch (1843 – 1910). In 1882, for instance, he tracked down the tuberculosis pathogen and in 1884 he identified the cholera bacterium. Koch's students then went on to make history by developing serum-based immunisation methods: these pioneers included Emil von Behring (1854 – 1917), Paul Ehrlich (1854 – 1915), Kitasato Shibasaburō (1853 – 1931) and Erich Wernicke (1859 – 1928). Back in the 19th century, it was already possible to see bacteria under the microscope because they are relatively large. But as yet, medical researchers did not realise that there are other pathogens, too: viruses, which are many times smaller than bacteria. Many vaccines were developed even though scientists did not yet fully understand how bacteria and viruses function.

 

Government vaccination programs

 

From the end of the 19th century onwards, pharmaceutical companies embarked on massive efforts to develop vaccines against various infectious diseases. And governments across the globe launched large-scale vaccination programmes for their populations, such as the 1914 campaign against typhus in the USA. The American virologist John F. Enders (1897 – 1985) ultimately developed a process that could also be used to contain infectious diseases caused by viruses, such as polio, measles and mumps. He was awarded the 1954 Nobel Prize in Physiology or Medicine for this achievement.

 

Then things really took off: in the 1960s, vaccines against diseases such as hepatitis became established. 1971 saw the market launch of a combined vaccine against the three widespread children's diseases – measles, mumps and rubella (MMR) – and it is still in common use today. The positive impact of mass vaccinations has been so spectacular that the Word Health Organization (WHO) has supported international vaccination programmes since 1967. This is leading to the disappearance of many diseases such as polio, which now exists only in Afghanistan and Pakistan. On the other hand, smallpox – on which Edward Jenner began his empirical vaccination experiments – has been eradicated: the last recorded case occurred in Somalia back in 1977. Even though science has now analysed viruses down to their genetic components and we have plenty of knowledge about how they function, they are still a burden to public health. The coronavirus is another forceful reminder of this fact.

Next Chapter

 

The journey to the coronavirus vaccine

 

All of us are impacted. Hoping for the vaccine. The race began in early January 2020 and Johnson & Johnson is only a few steps away from the goal. It's a feat of strength.

 

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