The two most important contributions to public health in the past 100 years—sanitation and vaccination—have markedly decreased deaths from infectious disease, and yet infectious diseases remain the leading cause of death worldwide. Modern immunology itself grew from the success of Edward Jenner’s and Louis Pasteur’s vaccines against smallpox and chicken cholera, respectively, and its greatest triumph has been the global eradication of smallpox, announced by the World Health Organization in 1979. A global campaign to eradicate polio is now well under way. With the past decade’s tremendous progress in basic immunology, particularly in understanding innate immunity, there is now great hope that vaccines for other major infectious diseases, including malaria, tuberculosis, and HIV, are within reach. The vision of the current generation of vaccine scientists is to elevate their art to the level of modern drug design; to move it from an empiric practice to a true ‘pharmacology of the immune system.’
The goal of vaccination is the generation of long-lasting and protective immunity. Throughout this book, we have illustrated how the innate and the adaptive immune systems collaborate in the face of infection to eliminate pathogens and generate protective immunity with immunological memory. Indeed, a single infection is often (but not always) sufficient to generate protective immunity to a pathogen. Recognition of this important relationship was recorded more than 2000 years ago in accounts of the Peloponnesian War, during which two successive outbreaks of plague struck Athens. The Greek historian Thucydides noted that people who had survived infection during the first outbreak were not susceptible to infection during the second.
The recognition of this type of relationship perhaps prompted the practice of variolation against smallpox, in which an inoculation of a small amount of dried material from a smallpox pustule was used to produce a mild infection that was then followed by long-lasting protection against reinfection. Smallpox itself has been recognized in medical literature for more than 1000 years; variolation seems to have been practiced in India and China many centuries before its introduction into the West (some time in the 1400s–1500s), and it was familiar to Jenner. However, infection after variolation was not always mild: fatal smallpox ensued in about 3% of cases, which would not meet modern criteria of drug safety. It seems there was some recognition that milkmaids exposed to a bovine virus similar to smallpox—cowpox—seemed protected from smallpox infection, and there is even one historical account suggesting that cowpox inoculation had been tried before Jenner. However, Jenner’s achievement was not only the realization that infection with cowpox would provide protective immunity against smallpox in humans without the risk of significant disease, but its experimental proof by the intentional variolation of people whom he had previously vaccinated. He named the process vaccination (from vacca, Latin for cow), and Pasteur, in his honor, extended the term
Fig. 16.22 Diseases for which effective vaccines are still needed. *Current measles vaccines are effective but heat-sensitive, which makes their use difficult in tropical countries; heat stability is being improved. Mortality data are the most recent estimated figures available (2014). Global Health Estimates 2000–2012. World Health Organization, June 2014.
to the stimulation of protection against other infectious agents. Humans are not a natural host of cowpox, which establishes only a brief and limited subcutaneous infection. But the cowpox virus contains antigens that stimulate an immune response that cross-reacts with smallpox antigens and thereby confers protection against the human disease. Since the early 20th century, the virus used to vaccinate against smallpox has been vaccinia virus, which is related to both cowpox and smallpox, but whose origin is obscure.