Developed by the Federation of American Societies for Experimental Biology (FASEB) to educate the general public about the benefits of fundamental biomedical research. INSIDEthis issue Vaccines: Essential Weapons in the Fight Against Disease The safer should be chosen 1 Germ theory and rabies averted 2 Magic bullets and devouring cells 3 In pursuit of polio 4 Subunit and conjugate vaccines 5 Vaccine safety 7 Recombinant vaccines 8 Taking its toll 9 The future of vaccines 10 Acknowledgments Vaccines: Essential Weapons in the Fight Against Disease Author, Margie Patlak Scientific Advisor, Nilabh Shastri, PhD, University of California Berkley BREAKTHROUGHS IN BIOSCIENCE COMMITTEE Paula H. Stern, PhD, Chair, Northwestern University Feinberg School of Medicine Aditi Bhargava, PhD, University of California San Francisco David L. Brautigan, PhD, University of Virginia School of Medicine Blanche Capel, PhD, Duke University Medical Center Rao L. Divi, PhD, National Cancer Institute, National Institutes of Health Marnie Halpern, PhD, Carnegie Institution for Science Edward R. B. McCabe, MD, PhD, March of Dimes Foundation Loraine Oman-Ganes, MD, FRCP(C), CCMG, FACMG, Sun Life Financial Sharma S. Prabhakar, MD, MBA, FACP, Texas Tech University Health Sciences Center R. Brooks Robey, MD, FASN, FAHA, White River Junction VA Medical Center and Geisel School of Medicine at Dartmouth Scott I. Simon, PhD, University of California Davis ad hoc Committee Member, Herman Staats, PhD, COVER: Vaccines are powerful weapons in the fight Duke University Medical Center against disease. They have averted more than 100 million cases of disease in the United States and continue to prevent 2.5 million deaths globally every year. By BREAKTHROUGHS IN BIOSCIENCE answering some very basic questions, such as what PRODUCTION STAFF enables a guinea pig to defend itself against a toxin, how do starfish and other animals without stomachs Managing Editor, Anne M. Deschamps, PhD, Senior Science process their foods, and what protects fruit flies from Policy Analyst, FASEB Office of Public Affairs fungal infections, researchers laid the foundation for an impressive vaccine armory to fight infectious diseases and cancers. Cover illustration: © Michael Linkinhoker, Link Studio, LLC This article was developed in collaboration with The American Association of Immunologists. VACCINESVaccines: Essential Weapons in the Fight Against Disease An ounce of prevention is worth a pound of cure. − Benjamin Franklin Imagine a world in which playgrounds and pools are closed because of polio BENJAMIN FRANKLIN epidemics, and elementary school playmates are dying from diphtheria Perhaps the most poignant or whooping cough, while others are advocate for variolation permanently left deaf, blind, or sterile (inoculation with the live due to measles, mumps, or meningitis. smallpox virus) was Benjamin Only a generation or two ago that Franklin. Franklin writes in his world was a frightening reality that autobiography, “I lost one of my contributed to one out of five children sons, a fine boy of four years old, never reaching adulthood in the United by the small-pox, taken in the common way. I long regretted States. Repeated epidemics swept bitterly, and still regret that I had through the world, killing as many as not given it to him by inoculation. one-quarter of the population, many This I mention for the sake of of whom were healthy and vibrant parents who omit that operation, before an infectious disease led them on the supposition that they to their graves. should never forgive themselves if a child died under it; my Fortunately, that world no longer example showing that the regret exists because of tremendous progress may be the same either way, and made in vaccine development and Image credit: Joseph-Siffrein Duplessis that, therefore, the safer should application. There are now more than (Public domain), via Wikimedia Commons be chosen.” two dozen vaccines that can prevent death or disability from infectious diseases such as influenza, polio, meningitis, and measles. Vaccines Although the first vaccines stemmed are showing promise in clinical tests. have prevented more than 100 million from observations made centuries In an age when global travel facilitates cases of disease in this country alone ago that survivors of epidemics were the rapid spread of deadly epidemics and continue to prevent 2.5 million naturally immune to the same disease, and antibiotic-resistant infections are deaths worldwide each year—the current vaccine successes come from becoming more and more common, equivalent of averting about 7,000 the efforts of hundreds of researchers vaccines are increasingly important deaths each day. With the exception over the last century and a half. By as powerful weapons against of safe drinking water, no other pursuing basic research, they uncovered infectious disease. single health measure has saved so what causes disease, how our immune many lives as vaccines. Vaccines system fights such illnesses, and ways also are highly cost effective. Routine The safer to harness and enhance our natural vaccinations administered to US should be chosen ability to combat infection. children between 1994 and 2013 are It is May of 1796 and, along with the estimated to save $295 billion in direct Basic research also fuels advances blooms of flowers, a deadly smallpox health care costs and an additional $1.3 in vaccines and underlies recent epidemic is sweeping across England. trillion in indirect costs ranging from breakthroughs, including innovative The disease is called the “speckled missed work to permanent disability. HIV, malaria, and Ebola vaccines that monster” because of the disfiguring 1 Figure 1 – Portrait of Edward Jenner inoculating boy: Jenner’s smallpox Figure 2 – Louis Pasteur vaccine slashed the incidence of smallpox in half throughout the world by the supervising rabies inoculation: time he died in 1823. Image credit: Wellcome Images/Science Source Pasteur’s discovery that injections of weakened viruses or bacteria protected people from the disease led to his successful creation of vaccines scars it leaves behind. It is killing more Four years after Jenner’s success, for rabies and other diseases. than three-quarters of infants, and one- physicians are using the revolutionary Image credit: National Library third of its survivors end up blind. smallpox vaccine throughout England of Medicine Hearing tales that milkmaids are and much of Europe, as well as in naturally immune to the disease after the nascent US. By the time Jenner suffering a milder cow pox rash, the dies in 1823, his vaccine has slashed animalcules” under his microscope English country physician Edward the incidence of smallpox in half a century before Jenner began Jenner hopes to offer similar natural throughout the world. By 1979, vaccinating. No one made the link protection to his patients. He finds a smallpox is eradicated worldwide, between Leeuwenhoek’s microbes young dairymaid with cowpox blisters such that smallpox vaccinations are and disease, but that changed in the and uses a lancet to insert the pus no longer deemed necessary for the 1870s when an epidemic began killing from her blisters under the skin of an general public. silkworms. The French chemist Louis eight-year old boy. The boy develops Jenner was unaware that microbes Pasteur had previously discovered a fever and loses his appetite, but he triggered disease and was acting that certain bacteria spoiled the broth fully recovers ten days later. That merely on the anecdotal observation of the fermenting grains and grapes summer Jenner gives the boy a similar that milkmaids were protected from used to make beer and wine. So the inoculation, but this time with pus smallpox. Further progress in vaccines silk industry in southern France asked taken from a fresh smallpox blister. wouldn’t come until nearly a century Pasteur if he could also figure out the As Jenner expected, the boy stays later when researchers began solving source of the epidemic in silkworms healthy and is one of the first to be an ancient puzzle: what causes that was destroying their operations. successfully vaccinated for smallpox. infectious diseases and how do our Pasteur’s microscopic observations of Jenner’s vaccine works because, bodies naturally fight them? the diseased worms and eggs revealed unknown to anyone at the time, the telltale spores of a parasitic fungus virus that causes smallpox is so closely and led him to the correct hypothesis related to the cowpox virus that the Germ theory and rabies averted that the disease could be prevented by experimental vaccine triggers an selecting silkworm eggs not infected immune response offering protection As late as the mid-nineteenth by the spores. from both. The term vaccination was century, infectious disorders were initially used to describe inoculation attributed to poisonous vapors, Shortly thereafter, Pasteur proposed his against smallpox using the cowpox planetary influences, or bad smells. germ theory, which postulated that all virus, but the term today signifies Anton van Leeuwenhoek gleefully infectious diseases were caused by tiny inoculation against any disease. reported seeing what he called “living organisms invisible to the naked eye Breakthroughs in Bioscience 2 called germs. The German physician Robert Koch made further refinements to the germ theory, set forth methods to determine whether a particular agent is responsible for disease, and triggered a worldwide hunt for disease-causing germs. Twenty years later, Pasteur, Koch, and other researchers had uncovered the origin of many common deadly diseases, such as leprosy, tuberculosis, cholera, and the plague. It was while trying to uncover the cause of an epidemic of cholera in chickens that Pasteur made one of the most important discoveries in the history of vaccines. He noticed by chance that old, weakened cultures of the causative bacteria he had isolated from infected chickens lost the capacity to cause major disease in poultry; however, chickens inoculated with the weakened bacteria no longer succumbed to more virulent strains in Figure 3 – Phagocytosis: Metchnikoff discovered that cells called phagocytes the wild.