Dr. Rappuoli is a pioneer in the world of vaccines and has introduced several novel scientific concepts. First, he introduced the concept that bacterial toxins can be detoxified by manipulation of their genes (genetic detoxification, 1987). Next, the concept that microbes are better studied in the context of the cells they interact with (cellular microbiology, 1996), and then the use of genomes to develop new vaccines (reverse vaccinology, 2000). In the process of reverse vaccinology the entire genomic sequence of a pathogen is screened using bioinformatics tools to help determine which genes code for which proteins, against which vaccines can be developed.
Dr. Rappuoli also worked on several molecules which became part of licensed vaccines. He characterized a molecule, CRM197, that today is the most widely used carrier for vaccines against Haemophilus influenzae, meningococcus and pneumococcus. Later he developed a vaccine against pertussis containing genetically detoxified pertussis toxin and the first conjugate vaccine against meningococcus C that eliminated the disease in the United Kingdom in 2000. His work on reverse vaccinology led to the licensure of the first meningococcus B vaccine approved in Europe and Canada in 2013 and USA in 2015.