Vaccination is an acknowledged powerful intervention to reduce mortality and morbidity caused by infectious diseases, preventing 2.5 million deaths each year as estimated by the World Health Organization. Despite the impressive success of modern vaccine programs, there is still a need to improve the effectiveness and safety of the current vaccine strategy. Without doubt, the site of the body where the vaccine is administered is of ultimate importance and it may very well be that the traditional intramuscular (IM) or subcutaneous (SC) methods are suboptimal. These vaccination routes have empirically been selected in the past without scientific evidence showing that these locations are the best to use. However, because of the large historical evidence that protective immunization is reached via these routes, the global health community still continues to use the muscle and subcutis as injection sites for the vast majority of present-day vaccines.

The use of skin to inoculate pathogens in order to establish protection was established several centuries ago, despite the lack of any immunological knowledge. The concept was based on proverbial wisdom and empirical evidence, but nevertheless inoculation (interchangeable with the term variolation) became tradition in parts of the word, such as the Turkish Ottoman Empire. Given the historical use, Edward Jenner (1749 – 1823) did not in fact discover vaccination. Jenner’s work, however, represented the first scientific investigation demonstrating that administration of cowpox in the skin protects against subsequent infection with smallpox, or in other words, his work convinced the scientific world that an infectious disease can be controlled by the deliberate use of vaccination.