Invention: Next-generation vaccines against meningitis, whooping cough and other infections
Infectious diseases such as diphtheria, bacterial meningitis and whooping cough have been practically eradicated in the developed world, thanks to Rino Rappuoli. Over the course of a research career spanning more than four decades, the Italian microbiologist has pioneered "conjugate vaccines" that have launched a new generation of immunisations, now administered to millions of people worldwide.
Before Rappuoli's game-changing inventions, vaccines contained "weakened" versions of actual pathogens that triggered the body into building immunity. But this approach, used since the late 1800s, yields no protection against aggressive infections such as meningococcus, the bacterium behind infectious meningitis. Shifting the paradigm, Rappuoli's "conjugate vaccines" are bio-engineered in the laboratory by attaching bacterial fragments to carrier proteins that elicit a strong immune response.
The vaccines, developed during Rappuoli's tenure at the Sclavo Research Centre in Italy, do not just offer an unprecedented level of protection. They have also become standard immunisations against a large number of infections including meningitis, diphtheria, whooping cough, haemophilus influenza and helicobacter, and are now administered to millions of people every year.
Rappuoli is credited with being one of the founders of cellular microbiology, where cell biology and microbiology meet. His techniques, including a process known as "reverse vaccinology" used to create the world's first genome-derived vaccines in 1999, have revolutionised vaccine design.
The impact of Rappuoli's invention can hardly be overstated: his vaccinations have been given to millions as part of routine programmes. First released in 1993 by California-based biotechnology company Chiron, his vaccine against pertussis (whooping cough) eradicated the disease in Italy within 24 months.
Rappuoli also made history in the late 1990s by developing and patenting the first-ever vaccines for each strand of meningococcal meningitis (A, B, C, Y and W-135). In the late 1990s, meningitis C was incorporated into the UK's national immunisation programme, virtually eradicating the disease within two years. In 2015, the meningitis B vaccine was also incorporated, with public health experts recently estimating that the vaccine is 95% effective. Meanwhile, meningitis is still rampant in resource-poor regions, where invasive meningococcal diseases (IMDs) still affect an estimated 1.2 million people every year.
Rappuoli's anti-meningitis vaccine, Bexsero, proved a blockbuster drug for licence owners GlaxoSmithKline. In 2016, sales of Bexsero reached EUR 465 million, nearly three-and-a-half times more than in 2015 (EUR 136 million). In the UK and other European countries, pneumococcal conjugate vaccine (PVC) is routinely administered to infants, while 82.9% of American children aged 19 to 35 months received the vaccine in 2014.
Analysts at Transparency Market Research valued the global meningococcal vaccines market at EUR 1.36 billion in 2013, projected to grow to EUR 4 billion per year by 2022. Within that market, conjugate vaccines and vaccines developed by reverse vaccinology are dominant forces, expected to account for 71% of total revenue (EUR 2.8 billion) by 2022.
Rino Rappuoli holding a journal about the value of vaccination
Rino Rappuoli with a diagram of his Meningococcus B vaccine
How it works
Rappuoli's "conjugate vaccines" take specific pieces of bacteria cells, namely surface sugars known as polysaccharides, and attach ("conjugate") them to carrier proteins.
These carrier proteins - such as a non-toxic protein obtained from diphtheria - are necessary components because surface sugars alone fail to build immune responses in children and infants. The proteins are made non-toxic in the laboratory through a targeted genetic technique called site-directed mutagenesis that introduces a mutation into a DNA sequence.
In the late 1990s, Rappuoli also introduced a fundamental new technology called "reverse vaccinology": vaccines no longer had to be based on laboratory-grown bacteria, but could be designed on a computer. Genomic sequencing of bacteria such as meningococcus B allowed Rappuoli to combine immunity-building components while "silencing" harmful effects.
As a young researcher, Rino Rappuoli was introduced to the world of cell biology during a research fellowship at the Sclavo Research Centre, an Italian immunisation think tank. Stints at Harvard and Rockefeller Universities acquainted him with cutting-edge genetic engineering techniques, which he evolved to achieve his own breakthroughs.
Rappuoli is the author of 150 granted and pending European patent families, 650 scientific papers, 60 reviews and 39 book chapters. Today, he is chief scientist at global pharmaceutical manufacturer GlaxoSmithKline Vaccines. His research focuses on finding vaccines for respiratory syncytial virus, cytomegalovirus and emerging infectious diseases.
Rappuoli has received numerous awards for his pioneering efforts in vaccine design and genetic research, including the Paul Ehrlich and Ludwig Darmstaedter Prize (1991), the Italian Gold Medal for Public Healthcare (2005), and the Albert B. Sabin Gold Medal (2009). He was voted the world's third-most influential person in the field of vaccines at the Terrapinn World Vaccine Congress in 2013.
Did you know?
When he was still very young, Rino Rappuoli was inspired to fight infectious diseases by the sight of the unfinished wall of Siena cathedral. The uncompleted building stands as a stark reminder of the year 1348, when the plague reduced the town's population from 100 000 to 30 000 in just three months.
Only a century ago, millions of people perished every year from diseases that are now entirely preventable through vaccination. Rappuoli's vaccines take their place in a long line of immunisations - against smallpox, tuberculosis and polio, for example - that have made the world a safer place.
Looking ahead, Rappuoli is concerned about the potentially devastating effects of an influenza pandemic. Whereas the 14th century "Black Death" took a whole year to spread, air travel means that recent outbreaks such as avian flu can proliferate within days. Fortunately, scientists can also engineer new vaccines faster than ever these days - thanks to Rappuoli.