Vaccination is potentially the most cost effective method of controlling infections.1 However, as the quests for safe and effective anti-HIV and anti-malarial vaccines show, successful development of vaccines is not easy. When HIV was identified, optimists thought that a vaccine would soon follow, perhaps within two years. Two decades later, that goal seems to be as elusive as ever. Moreover, worldwide eradication of a disease—although possible, as shown with smallpox—presents logistic and economic challenges. People who need the vaccines are most often least able to pay for them or use them properly, because of educational barriers or woefully inadequate healthcare systems.

Most vaccines are administered by injection. Effective non-parenteral vaccines would be more convenient and potentially cheaper to produce and administer. Why then are so few such vaccines available? For example, in the United Kingdom, despite intense research, only the Sabin oral polio vaccine is in general use. In a survey of the field nine years ago I was optimistic and foolhardy enough to believe that soon many of the parenteral vaccines would be administered via alternative routes.2

With better understanding of the immune system, notably at mucosal portals of entry, recognition of …