The genome as a gold mine

Rino Rappuoli has written medical history with a new method for producing vaccines

13. June 2019

The 2019 Robert Koch Award goes to Rino Rappuoli from Italy/
the US American Martin J. Blaser receives the Robert Koch Gold Medal

Berlin – The Robert Koch Foundation will present the 2019 Robert Koch Award, with an endowment of 120,000 euros, to Professor Rino Rappuoli, Chief Scientist and Head of External Research and Development (R&D) at GlaxoSmithKline (GSK) Vaccines in Siena, Italy. The award honors his ground-breaking work on the development of novel vaccines.

Professor Martin J. Blaser, Director of the Center for Advanced Biotechnology and Medicine (CABM) at Rutgers Biomedical and Health Sciences (RBHS), Henry Rutgers Chair of the Human Microbiome and Professor of Medicine and Microbiology at the Rutgers Robert Wood Johnson Medical School in New Jersey (US), receives the Robert Koch Gold Medal for his life’s work, in particular for his work on the biology of Helicobacter pylori.

The award and the honorary medal will be presented at an official ceremony on November 15, 2019 at the Berlin-Brandenburg Academy of Sciences and Humanities in Berlin.

Photos and CVs of the laureates:
>>Rino Rappuoli
>>Martin J. Blaser

Robert Koch Award

For Rino Rappuoli, developing a new type of vaccine has always been a matter of great personal importance. Every time when in his native Siena he passed the façade of the “New Cathedral”, which was never completed, he was reminded of the year 1348, when the Plague carried off two-thirds of the population within just three months. The technological and artistic development of the city came to an abrupt halt. “Such a thing should never happen again”, says Rappuoli, “so I decided to devote my entire life to developing vaccines.” His work has paid off. Rino Rappuoli has written medical history with a series of spectacular achievements. The “reverse vaccinology” developed by him, which works on the principle that one starts with the genome of a pathogen, rather than laboriously creating it in the laboratory, was a paradigm change.

In the early 1990s, Rappuoli first caught the attention of scientists worldwide with a vaccine against whooping cough (pertussis). The vaccine, for which he had neutralized the pertussis toxin using genetic technology, was among the new generation of so-called “acellular” vaccines, and was far more compatible than the whole-cell vaccines used up until then. Two years after it was introduced in Italy in 1993, the disease was considered to have been practically eliminated. “So that is basically one of the most beautiful things that can happen if you do my job”, says Rappuoli. “That’s been my motivation ever since.”

Rappuoli’s many years of working with the meningococca that can cause meningitis or sepsis have been dominated by his creative imagination and the unbending will to make even what appears impossible a reality. He developed the first “conjugate vaccine” against Type C “Neisseria meningitidis”. A polysaccharide from the bacterial capsule was coupled (“conjugated”) to a carrier protein in order to improve the effectiveness. In Britain, it was possible to practically eliminate the disease with this vaccine in a nationwide campaign.

The serotype B bacterium, which is responsible for around half of all meningitis cases worldwide, presented an even greater challenge. Since the only polysaccharide on its capsule is similar to certain sugar structures on human cells, our immune system does not produce antibodies against it. For this reason, another solution had to be found. Rappuoli contacted Craig Venter, who had sequenced the entire genome of an organism for the first time in 1995 with the genome of Haemophius influenzae. Venter said that he was willing to also take on the challenge of sequencing the genome of “Neisseria meningitidis B”. In 2000, they achieved a result, and Rappuoli knew that “we had a kind of gold mine in our hands”.

Of the 600 or so probable surface proteins that he had succeeded in nailing down on the computer in collaboration with British molecular biologists, 91 turned out to be potential vaccine candidates. A good two-dozen were then eligible for the shortlist following tests on laboratory mice; three were then finally used in “Bexsero”, the first vaccine against Type B meningitis. The vaccine was authorized for use in 2013 in Europe, Canada and Australia, and in 2015 in the US, and became a blockbuster for license owner GlaxoSmithKline (GSK).

Rappuoli is one of the co-founders of “cellular microbiology”, which combines cell biology and microbiology under one roof. In 2009, with the aid of MF59, the first new vaccine booster (“Adjuvants”) since aluminum salts were introduced in the 1920s, the first vaccine against swine flu (H1N1) was produced under his leadership. In 2013, Rappuoli and Craig Venter developed the first RNA vaccine against influenza and the first synthetic vaccine against the H7N9 bird flu virus. In light of the threat of a flu pandemic, the memory of the Plague in Siena, which decimated the population, which was reduced from 100,000 to just 30,000, was more than just an historical metaphor for the Italian. “I see it as an example of what could happen today with pandemic influenza.”

In 2005, Rino Rappuoli received the Italian Gold Medal for Public Healthcare, in 2009 the Albert B. Sabin Gold Medal, in 2017 the Canada Gairdner International Award, and the European Inventor Award for his life’s work. As a top researcher for a global player among vaccine developers, he also feels a sense of responsibility. To reduce the gap between the rich and poor countries, the Novartis Vaccines Institute for Global Health was founded in Siena in 2008 on Rappuoli’s initiative (today: GSK Vaccines Institute for Global Health/GVGH). The aim of the non-profit organization is to develop vaccines against neglected diseases and to make them available to third-world countries at affordable prices.

Robert Koch Gold Medal

Martin J. Blaser always says that the most important thing in life is to follow your inner voice, when young colleagues ask for some parting advice: “Follow your nose, and see where it leads!” Blaser’s life’s work is an impressive example of just how far this attitude can take you. He was around during the mid-1980s when Barry Marshall, who would later be awarded a Nobel Prize, reported on the sensational discovery that the bacterium Helicobacter pylori can trigger stomach ulcers. When he heard this, Blaser knew that he had found the subject to which he wanted to devote his life. Like most of his medical colleagues, he was also convinced at first that the germ had to be eliminated in order to permanently banish the malady from the world.

Blaser, who was working at the Vanderbilt University School of Medicine in Nashville at the time, played a key role in the development of the first blood test for H. pylori. He contributed the important information that the bacterium can also cause stomach cancer. Using the so-called “CagA protein” and the associated gene, he discovered one of the most important virulence factors. However, was it really such a good idea to do away entirely with the rod bacterium with its spiral curved form?

Once Blaser had asked himself this question, he couldn’t stop thinking about it. When he first posited in the “Lancet” in 1997 that Helicobacter pylori might also have its good sides, he was met with vehement criticism. As one of the most prominent gastroenterologists at the time said: “The only good Helicobacter pylori is a dead Helicobacter pylori”. However, Blaser wasn’t put off. In 1998, he set up the “Foundation for Bacteria” in order to promote broader studies on the complex role of bacteria. Blaser and his team found the first indications that a colonization of the human stomach with H. pylori can protect against serious diseases of the esophagus, including esophageal cancer. And there were strong indications that it also helped prevent asthma among children.

“All of a sudden, the biological relationship got more complex”, Blaser remembers, when he looks back at this paradigm shift. “Here was an organism that could do both harm and good. And it became clear that it was disappearing along with modern life. And this had consequences for disease risk.” Martin J. Blaser was convinced that the main reason for this was antibiotics. It is thanks to him that we are now aware of these negative consequences of overuse of antibiotics. “It is wonderful that we have these medicines. They fight microbes that make us sick and that can kill us. However, we now know about their negative impact. The antibiotics damage all of these helpful microbes. It’s a kind of collateral damage. And until now, we hadn’t taken these consequences into account.”

Using animal experiments and epidemiological studies, Blaser, who now worked at the Department of Medicine at New York University, began to focus on the importance of a healthy microbiome for development in early childhood – and on the damage caused when antibiotics are taken too frequently, precisely in this sensitive phase of life. In his much-quoted essay “What are the consequences of the disappearing human microbiota?”, which he published in 2009 together with the American microbiologist Stanley Falkow, he warned against a fatal “extinction” in the human microbiome that had led to a massive increase in diseases occurring in modern civilization, such as diabetes, asthma, obesity and food allergies. The experiments conducted in his lab showed that early life antibiotic exposures could play causal roles in obesity, juvenile diabetes, and inflammatory bowel disease through a perturbed microbiome. In his book “Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plague”, Blaser made his work available to a broader readership, now translated into 20 languages. A year after this book was published in the US, the US magazine TIME included him in the list of the “100 most influential people in the world” for 2015. As a scientist and author, Martin J. Blaser was an “incredibly important voice on the consequences of our rampant overuse of antibiotics”. And: “If you care about your health and the future of medicine, read Blaser’s book.”

About the Robert Koch Foundation

The Robert Koch Foundation is a non-profit foundation dedicated to the promotion of medical progress. It was founded in 1907 and is based in Berlin. The Foundation promotes basic scientific research in the field of infectious diseases, as well as exemplary projects that address medical and hygienic issues.

The Foundation confers a number of distinguished scientific awards each year: the Robert Koch Award – one of Germany’s most distinguished scientific awards, the Robert Koch Gold Medal, three awards for young scientists and, since 2013, the Hospital Hygiene and Infection Prevention Award.

Robert Koch (1843 – 1910), after whom the award is named, was the founder of modern-day bacteriology, for which he was awarded the 1905 Nobel Prize for Medicine and Physiology. From 1891 until his retirement in 1904, Koch was Head of the Institute for Infectious Diseases in Berlin.

Christine Howarth, Tel. +49 (0)30-468-11599, E-Mail: