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A Brief History of Vaccine Developments

A Brief History of Vaccine Developments

Earliest “Vaccine” on Record

The earliest informal and regulated vaccines on record are for smallpox. In Asia, the process of variolation, as vaccination was called at that time, emerged where a smallpox scab would be dried, ground into powder, and blown into the nose of the person, thereby “vaccinating” him or her. It was intended that the vaccinated person would then contract a mild form of the disease after which they would be immune to the virus that causes smallpox. Variolation was first reported in 15th century China and subsequently in Africa, Europe and the Americas. It was risky: the vaccinated patient could die from smallpox and could spread the disease and start an epidemic.

While variolation was risky and fraught with problems, it demonstrated that human immune responses could be trained to recognize the smallpox virus, that human immune responses had “memory” and that once the human immune system had initially succeeded in killing the virus the first time, the human immune system remembered how to kill the virus when subsequently exposed to infection. Such lessons inspired the physician scientist Dr. Edward Jenner to note that people exposed to cowpox, a virus related to smallpox that does not cause human disease, were immune to smallpox – exposure to cowpox prevented smallpox. Dr. Jenner then began to vaccinate people with the cowpox virus. After vaccinating people with cowpox, Dr. Jenner next infected these people with smallpox and demonstrated that they were protected from smallpox. Dr. Jenner completed this first vaccine study in 1798, and is recognized as the father of immunology by demonstrating the powerful role that human immune responses play in protecting us from infectious disease.

The Early Need for a Vaccine

Life expectancy throughout the world in 1800 was approximately 30 years of age and today it exceeds 70 years of age. Vaccines, antibiotics, and water treatment are three factors that greatly contributed to this more than doubling of our lifespan. Looking at smallpox, we can see that the decline of the Roman Empire, the Incan Civilization and the Aztec Empire were all related to smallpox epidemics. Estimates indicate that as many as 30% of infected people died while those that survived were often terribly disfigured. This ugly disease was found in human populations very early. Pharaoh Ramses V who died in 1157 BCE was thought to have had smallpox. And, it is estimated 300 million people died of smallpox through the 1900’s. Even more frightening was that smallpox primarily infected children such that families did not consider children full members of the family until they survived a smallpox infection. Families could do nothing but watch the infection run its course and hope their children survived. In short, vaccines improve the quality and duration of life.

The Adoption of Vaccines across the World

Because it was such a scourge on society for such a long time, and because Dr. Jenner had successfully tested a smallpox vaccine, the smallpox vaccine was the first widely adopted vaccine. Historically, new medical developments divide public opinion, and the smallpox vaccine was no exception. Vaccine immunizations such as smallpox have been opposed since their inception. Some of the resistance is human nature – jealousy, not all contributions dully recognized, resistance to change – while some resistance may have been driven by gain or loss of income; greed. Following Dr. Jenner’s initial and controversial success, Dr. Louis Pasteur developed a Cholera vaccine in the 1800’s and the 1900’s brought the development of a tetanus vaccine, a whooping cough vaccine, the Salk and Sabin Polio vaccines, and additional vaccines for measles, mumps and rubella. Today, nine vaccines are given in the U.S. in the first 18 months of life with an additional seven vaccines by the age of 18. There seems to have always been resistance to vaccines, and the 1986 U.S. National Vaccine Injury Compensation program was implemented to ensure that vaccine manufacturers could limit litigation.

Vaccines in the Twenty-First Century

The biggest change in vaccine technology comes from a combination of new developments. First, as seen with the COVID-19 RNA vaccine, new vaccine delivery platforms are emerging. These platforms come from the collaborative effort of academic studies, biotech startups, and large pharmaceutical companies. Second, we see that these three parties (academia, biotech, large pharma) continue to better understand how the human immune system targets a pathogen: does the entire pathogen need to be included in a vaccine, or can we learn exactly which portion of a pathogen must be included in a vaccine in order to elicit protective immunity and at the same time to simplify the vaccine manufacturing process? With COVID-19 we see a very “clean” vaccine where only a small portion of the COVID-19 virus is placed into a very straightforward RNA vaccine platform. The COVID-19 pandemic has demonstrated the importance of working together, and it is reasonable to expect that future vaccines will be even more advanced in the selection of that portion of a pathogen to incorporate onto vaccine platforms that are elegant in their simplicity.

William Hildebrand, PhD, a George Lynn Cross Research Professor in the OU College of Medicine Department of Microbiology & Immunology, contributed to this article. For more information about the COVID-19 vaccine, visit