Vaccines are “immunogenic formulations” intended to protect vaccinated individuals by inducing production of antibodies and cell-mediated immune responses to combat infectious (and sometimes noninfectious) conditions. Historians trace the roots of modern vaccinology—the science of vaccine development—to the dicey practices of smallpox inoculation and variolation that began in the 1700s. About a century later, in 1885, Pasteur developed and administered a rabies vaccine to humans. Although these and other early vaccines produced mixed real-world results and generated warnings of potentially serious postvaccinal complications, mass vaccination nonetheless took off without a backward glance.
Even from the beginning, vaccination’s most avid proponents acknowledged the complex challenge of generating vaccine-mediated protection. The annoying persistence of vaccine failure prompted vaccine scientists to experiment continually with new vaccine technologies and move beyond the “three I’s” originated during Pasteur’s era (“isolating infectious agents, cultivating and inactivating them…and injecting the obtained product”). Twenty-first-century vaccine developers now draw on cutting-edge fields and techniques such as genetic and protein engineering, immune profiling, synthetic biology, combinatorial chemistry and bioinformatics. Their end goal is to “circumvent” a number of befuddling obstacles, including “hypervariable viruses,” pathogens that require repeat immunization, heterogeneous individual- and population-level vaccine outcomes—and declining public confidence in vaccine safety—to ensure seamless expansion of the modern vaccine “armamentarium.”