The first vaccination in the United States happened July 8, 1800, in Boston, when physician Benjamin Waterhouse administered the new smallpox vaccine to his five-year-old son, Daniel. And it worked. In the more than 200 years since, vaccines have proved themselves time and again to be safe, efficient and compellingly effective—especially in saving the lives of children.

But in recent decades, a troubling and misplaced fear of vaccines has spread throughout society, causing far too many to reject what is arguably the best weapon available to prevent deadly disease. An effective vaccine for Lyme disease, for example, was introduced in 1998, but it failed because of public skepticism and the threat of lawsuits. Meanwhile, known pathogens continue to spread and new infections emerge because of such factors as climate change, human encroachment and overcrowded living conditions.

Developing vaccines to combat new diseases takes time and ingenuity. Some efforts, like creating a universal flu vaccine, have not yet succeeded, though promising studies are bringing that goal within sight. In addition, new techniques that leverage advances from many fields—including genomic sequencing, computer modeling of proteins and new ways of measuring cell function—could trim years, and possibly decades, from the traditionally tedious vaccine development process. (“To Build a Better Vaccine”).

Central to the next generation of safe and effective vaccines will be a more precise understanding of the immune response. The Ragon Institute, a pioneering collaboration among Massachusetts General Hospital, MIT and Harvard, received a record donation of $200 million this spring from Phillip and Susan Ragon. This flexible funding enables scientists to pursue bold and unconventional ideas for harnessing the power of the immune system to treat and prevent some of the world’s most devastating human diseases. The Ragon Institute has been close on the trail of an HIV vaccine, with one candidate currently being tested in a large efficacy trial in Africa. The researchers at Ragon have also used these resources to make progress on a universal flu vaccine and are exploring vaccine technology as a way to treat solid tumors.

We need to continue to build upon our understanding of the body’s immune response to pathogens, and we need new ideas about how best to fortify the vital first line of defense. Indeed, at stake are millions of lives that could be saved by the next vaccine . . . and the next.