Vaccines for the 21st century

Abstract

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines.

Keywords: adjuvants; clinical trials; infectious diseases; structural vaccinology; vectors.

Figure 1. Major milestones in the historical path of the development of vaccinology and vaccine design

A method for preventing naturally acquired smallpox called ‘variolation’ was discovered in India before 1,000 A.D. and was in use also in China and Western Asia. This method, which consisted of the inoculation of pustule material from smallpox-infected patients to healthy individuals, was introduced in Europe in 1,721 by Lady Mary Wortley Montagu. The first real vaccination practice was introduced when Edward Jenner used pustule material from humans infected by cowpox to protect against smallpox.

Figure 2. Target disease and target populations for 21st century vaccine development

Included in the list are the agents of infectious diseases for which vaccines are not yet available or for which more effective vaccines would be beneficial. Also included are therapeutic vaccines for chronic infectious diseases, as well as non-communicable pathologies such as autoimmune diseases, cancer, and allergy, some of which are in advanced clinical trials.

Figure 3

The 21st century vaccinologists toolbox