Understanding the way in which hosts and pathogens interact began to unravel some of the mysteries of infection and disease. This led to the concept of

‘natural immunity’ to infection, which was indispensable for vaccine design. In 1908, Metchnikoff was awarded the Nobel Prize in Medicine jointly with Paul Ehrlich for their work on the theory of immunity. At the end of the 19th century, many of the fundamental aspects of vaccinology were in place because INCB024360 nmr of the pioneering work of scientists like Pasteur, Koch, Metchnikoff and Ehrlich. The most important advance was the demonstration that the administration of pathogens, either attenuated or inactivated, resulted in protection against the disease caused selleck kinase inhibitor by the respective native pathogen. Developments

in pathogen attenuation processes led to consistent production of attenuated microbes, and many of the vaccines employed today are still based on these developments. Figure 1.8 shows the various vaccine technologies developed over time. At the end of the 19th century, Émile Roux and Alexandre Yersin discovered that diphtheria and tetanus bacilli produce soluble molecules called exotoxins, which caused the symptoms of these infections. Soon after this discovery, Emil von Behring and Shibasaburo Kitasato postulated the serum antitoxin concept. The use of the term ‘immunisation’ dates from this work, referring to the rabbit serum that contained the antitoxin as immune serum. First Nobel Prize in Medicine The discovery of antibodies in 1890 and passive immunotherapy of diphtheria was honoured in 1901 when the first Nobel Prize in Medicine was awarded to Emil von Behring. In 1924, Gaston Ramon, a veterinarian at the Pasteur Institute, applied chemical inactivation to bacterial toxins to produce toxoids of diphtheria and tetanus. By this method, he transformed the

tetanus toxin with formaldehyde and heat into a safer, non-toxic product, without changing its immunogenic potential. He called this chemically treated product ‘anatoxin’ (ie toxoid). This discovery was also applicable to the toxin produced by the diphtheria bacillus. The diphtheria toxoid produced by Oxymatrine this method was used in a vaccination programme to greatly minimise fatal cases of diphtheria in infants. The tetanus toxoid vaccine was widely used to prevent tetanus from battle wounds sustained during World War II. The introduction of tetanus vaccination has almost eliminated the number of cases in developed countries; however, tetanus remains a problem, largely in the developing world ( Figure 1.9). Worldwide annual deaths in 2004 from tetanus were estimated to be 163,000, 144,000 of which occured in children less than 5 years of age ( WHO, 2009).