Maria Lattanzi and Rino Rappuoli
Infectious diseases are one of the most terrible enemies mankind has faced during its whole history. They have changed human fate and the course of history and have influenced national economics more than any war.
There are many examples that can be cited to assess the consequences of infectious diseases on the economic development of societies. Paradigmatic is what happened in Siena in 1348, when plague struck with unprecedented cruelty. In the 14th century, Siena, a city located on the way from Rome to France and Northern Europe, had one of the most powerful economies of its time. The wealthy inhabitants planned to build the largest cathedral in history whose construction started in 1338. Unfortunately, after only 11 years, in 1347, the plague (also called the 'Black Death') appeared in Northern Europe and killed 30 per cent of the European population. In May 1348 the epidemic spread to Siena where more than two-thirds of the inhabitants died within three months, including most of the masons and carvers who were building the cathedral. Today, the remainder of the unfinished original construction is still visible and can be considered 'a monument to infectious diseases'.
In 1300, vaccines were not available, and Siena did not have the choice of preventing the plague. Only recently has mankind managed to partially control infectious diseases thanks to the discovery and development of antibiotics and vaccines. The new technologies to develop vaccines available today have the power to achieve even much more spectacular results in the fight against infectious diseases.
Genomics, Proteomics and Vaccines edited by Guido Grandi © 2004 John Wiley & Sons, Ltd ISBN 0 470 85616 5
1.2 Vaccination: the past
The observation that people who survive an infectious disease do not relapse into the same disease again is extremely old. The historian Thucydides, describing the Peloponnesian War, reports that during the plague in Athens in 430 B.C. it was a common practice to use those who had recovered from the disease to take care of the sick, because 'the same man was never attacked twice' (Silverstein, 1989). Many authors have reported this observation since then, among them Procopius (541 A.D.), Fracastoro (1483-1553) and Alessan-dro Manzoni (1785-1873). Describing the terrible plague that killed half of the population in Milan in 1630, Manzoni reported that 'those who had recovered were quite a privileged class' because they could walk without fear anywhere, while the rest of the population were hiding themselves, fearing the constant risk of infection and death (Manzoni, 1972).
Nowadays, naturally acquired immunity to diseases, the basic principle of vaccinology, is common knowledge. However, practices of inducing artificial immunity by deliberate infection of healthy people are also very old. Variola-tion, the transfer of infected material from a smallpox lesion to healthy people to make them resistant to subsequent exposures to this deadly disease, was used in 590 A.D. in Asia. However, it had probably been practiced a long time before then. During the Middle Ages, the practice was spread to southwest Asia, the Indian subcontinent, North Africa and Turkey. The first half of the 18th century saw an extensive diffusion of variolation in Europe, and especially in the United Kingdom the reports of the miracles of variolation to the English Royal Society by Emanuele Timoni (family physician of the British ambassador in Costanti-nopolis) and Jacob Pylarini (Venetian Consul in Smyrna). A few years later, Lady Mary Montagou, wife of the British ambassador in Turkey, promoted this practice so efficiently that the sons of the Royal Family were variolated in 1722.
The practice was nevertheless a desperate undertaking, because up to four per cent of those variolated developed a severe, fatal form of the disease. However, this was much lower than the 20-30 per cent fatality rate from natural small pox.
A more successful approach came in 1796 with Edward Jenner, an English physician. During his practice in the countryside, he had noticed that farmers exposed to infected materials from cows did not develop the disease but acquired immunity to smallpox. Jenner decided to use the less dangerous material derived from the bovine (vaccinus) lesions to 'vaccinate' a boy (James Phipps) and showed that he was immune to a subsequent challenge with smallpox. The scientific approach to vaccination came only a century later, when Louis Pasteur introduced the concept that infectious diseases were caused by micro-organisms. Using this empiric approach he developed the first vaccine against rabies, which on 6 June, 1885, was successfully used to inoculate Joseph Meister, an Alsatian boy bitten by a rabid dog (Silverstein, 1989; Ada, 1993). Large-scale vaccination was adopted only following the discovery of a safe and reproducible way to inactivate toxins and pathogens with formaldehyde treatment, performed by Glenny and Hopkins in 1923 and Ramon in 1924, and of the stable attenuation of pathogens by serial passage in vitro.
From 1920 to 1980, these simple, basic technologies were used to develop vaccines that controlled many infectious diseases (Table 1.1). The achievements of this period have been remarkable. The introduction of routine mass vaccination is responsible for the eradication of smallpox virus in 1977, and poliomyelitis is expected to be eradicated by 2005. Moreover, the incidence of
Table 1.1 Vaccines introduced in routine immunization programs before the 1980s
Pertussis (whole cell) 1953
Meningococcus (capsular polysaccharide) 1969
Max. N of cases (year)
N of cases in 2001
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