The history of vaccination clearly demonstrates that vaccines have been highly successful in preventing infectious diseases, reducing significantly the incidence of childhood diseases and mortality. However, many infections are still not preventable with the currently available vaccines and they represent a major cause of mortality worldwide. In the twenty-first century, the innovation brought by novel technologies in antigen discovery and formulation together with a deeper knowledge of the human immune responses are paving the way for the development of new vaccines. Final goal will be to rationally design effective vaccines where conventional approaches have failed.

In the last century, vaccines demonstrated to be a successful and effective medical intervention representing one of the most important applications of immunology to prevent infectious diseases. A landmark in the history of immunology is the experiment conducted by Edward Jenner in 1796, when he demonstrated that inoculation with pus from cowpox lesions was conferring protection against smallpox infection providing an innovative contribution to immunization and the ultimate eradication of smallpox. Smallpox was one of the most severe human diseases, responsible only in Europe for the death of more than 400,000 people per year. In 1979, smallpox was eradicated through a global vaccine administration campaign. Jenner’s work was further refined by Louis Pasteur, who artificially attenuated viruses for use in vaccines and in 1885 developed the first rabies human vaccine. He brought a breakthrough in the prevention and treatment of infectious diseases by establishing the basis of vaccinology, meaning the principle of isolation, inactivation, and administration of disease causing pathogens. The Pasteur’s principles have allowed the development of “first generation” vaccines based on whole microorganism killed or live-attenuated (e.g., Bacillus Calmette Guerin BCG, plague, pertussis, and smallpox).

In the second half of twentieth century improvements and innovation in mammalian cell culture technology led to the growth of viruses and development of live attenuated “second generation” vaccines such as polio (Sabin oral), measles, rubella, mumps, and varicella. More recently, the use of inactivated polio vaccine (Salk type) together with oral vaccine has almost eradicated polio from the world thanks to global vaccination. In developed countries national immunization programs have drastically reduced most of the viral and bacterial infections that traditionally affected children. In May 2012, the 194 Member States of the World Health Organization Assembly endorsed the global vaccine action plan (GVAP) with the vision of delivering universal access to immunization, with at least 2–3 million lives saved per year worldwide.

Although traditionally developed vaccines have been in the last century of unquestionable value, saving more than 700 million cases of disease and more than 150 million deaths, the conventional methods of vaccine design have some limitations. For example, they could not be used to develop vaccines against microbes that do not grow in vitro (e.g., Mycobacterium leper, papilloma virus type 16 and 18). They do not provide broadly protective vaccines against pathogens with antigenic hypervariability (e.g., serogroup B meningococcus, HIV, HCV) or against pathogens with an intracellular phase, causing infections that are predominantly controlled by T cells, such as tuberculosis and malaria . Finally, traditional approaches of vaccine development can be very slow and time consuming, not allowing a rapid response to the need of a new vaccine, as in case of an influenza pandemic.

Conclusion

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