Rino Rappuoli
Chiron Vaccines, Via Fiorentina
1, 53100 Siena, Italy
Since the beginning of vaccinology,
more than two centuries ago, we have grown pathogens in animals (smallpox),
in eggs (influenza), or in the laboratory using a variety of media and fermentation
technologies. The grown pathogens have been used as live attenuated vaccines,
as killed vaccines or as a source of material for the discovery and manufacturing
of antigens to be used in subunit vaccines.
The availability of the genomic
sequence of most pathogens allowed for the first time to discover vaccines
without the need to grow pathogens. Vaccine discovery can be done in silico,
starting from the computer analysis of the genomes (reverse vaccinology).
Genome-based vaccine discovery
was applied for the first time to serogroup B meningococcus, a bacterium which
is a major cause of sepsis and meningitis, that had been resistant to all
conventional approaches to vaccine development. The sequence of the genome
allowed the in silico prediction 600 potential antigens. 350 of them were
expressed in Escherichia coli, purified and used to immunize mice.
29 were found to induce bactericidal antibodies, a property which correlates
with protective immunity. A subgroup of the genome-derived antigens are now
being tested in clinical trials.
Today reverse vaccinology is
a standard technology. No vaccine project is started without knowing the
sequence of the pathogen. Successful examples of genome-based vaccine discovery
are pneumococcus, group B streptococcus, Staphylococcus aureus, and
a variety of viruses. Coupled with the advances in the understanding the
molecular basis of the immune response and the development of new adjuvants,
the new technologies represent a quantum jump in vaccine discovery.