By Paolo Miguel Magallanes Mallorca

Vaccines! Everyone is talking about it lately. We may see them as the way out of this dreadful pandemic that made 2020 a mess. The good news is that some COVID-19 vaccines are approved and now being distributed to billions of people on this planet. With the vaccines making headlines, have you ever wondered where and how do vaccines originate?

“Vaccination” Before Dr. Edward Jenner

The earliest sign of “vaccination” was documented in ancient China and India, in the 10th Century [1]. The idea was to collect smallpox samples from blisters of a sick individual and inoculating minute amounts on healthy individuals. This practice wasn’t called vaccination but “variolation” (after the smallpox virus Variola major). It spread across some countries in Asia and Africa, eventually reaching Britain and other parts of Europe in 1721 [2]. While it was quite effective at protecting people from smallpox and controlling outbreaks, inoculated individuals still have a small risk of developing smallpox or other diseases transmitted by this procedure [2].

Dr. Edward Jenner: The Pioneer of Vaccines

In the 1700s, some milkmaids were reported to have immunity against smallpox. This was likely due to prior infection with cowpox, a disease similar to but milder than smallpox. In 1796, English physician Dr. Edward Jenner proved this observation by inoculating an eight-year-old boy with cowpox. The boy only developed fever and minor symptoms. After his sickness subsided, the boy was exposed to smallpox samples but did not developed the disease. After publishing the results of the experiments, Dr. Jenner called this procedure “vaccination” (derived from the latin word vacca, meaning cow) and it became more popular than variolation [2]. Countries in Europe began to enforce vaccination and saw significant decline in mortality rate [1].

Dr. Louis Pasteur: The Father of Immunology

While Dr. Louis Pasteur is well known for pasteurization, a method to reduce the load of microbial pathogens in food by heat, little attention is given to his other contribution: live-attenuated vaccines. Inspired by Dr. Jenner’s works, he suggested that there can be vaccines for other diseases as well.

In 1877, positing that vaccines could be found for all virulent diseases, Dr. Louis Pasteur attempted to work on chicken cholera [3], a bacterial disease that was devastating chicken populations. One time before going on a holiday, he instructed his assistant to inoculate chickens with fresh bacterial samples. The assistant forgot and upon returning, he inoculated the chickens with samples that had been sitting in the laboratory for a long time. The inoculated chickens survived, and remained healthy upon exposure to fresh samples afterwards. It was later discovered that the old samples were probably weakened due to prolonged exposure to oxygen, but could still induce immunity. This is the first example of a live-attenuated vaccine.

Dr. Pasteur’s accidental discovery of the chicken cholera vaccine inspired him to work on other diseases. In 1885, he worked on rabies, a fatal neurological disease in dogs and humans. It was discovered that growing rabies virus in other hosts like rabbits where the microbe does not normally propagate for more than several generations (scientifically termed serial passage), could weaken their virulence to the original host [3]. Through this method, weakened viral strains were collected and tested on dogs. After they successfully induced immunity in dogs, Dr. Pasteur tested the same strains on a boy who was bitten by a rabid dog. The boy did not show rabies symptoms.

Dr. Pasteur’s work shows that weakened pathogens may induce immunity against the disease they cause. This treatment was also named vaccination, which was originally referring to only smallpox, to honor Dr. Jenner’s previous work [3].

Modern Vaccine Development

Breakthroughs in microbiology and molecular biology in the 20th century drove the development of more vaccines. Not only there were vaccines available for more diseases, but there were new methods of creating vaccines and new types of vaccines as well.

It was discovered that pathogens carefully killed by heat or chemical treatment can induce immunity, creating inactivated vaccines. The first successful inactivated vaccines were created in the 1890s against typhoid fever and plague. This technique was expanded to viruses as well, and by 1936, a vaccine for influenza was invented [4].

Inactivated vaccines and live-attenuated vaccines are referred to as first-generation vaccines. The second-generation vaccines are subunit vaccines. Unlike the former generation, which uses whole pathogens, subunit vaccines use components of the pathogen that can be targeted by the immune system to develop immunological memory [4]. With the recent advances in genetic engineering, one variant of subunit vaccines uses recombinant DNA technology to mass-produce these components in other organisms or cells, such as yeast, animal cells and insect cells [4].

Then is the relatively new, third generation of vaccines. Instead of administering patients with whole pathogens or their components, genetic materials coding for those components in the form of DNA or mRNA are used. These genetic materials will be read by cells as instructions to produce viral components for the immune system to target. Due to the COVID-19 pandemic, both DNA and mRNA vaccines are receiving a lot of attention lately, which are the first of their kind to be approved for emergency use in humans. The development of DNA and mRNA vaccines was spurred unprecedentedly by the race to develop vaccines against COVID-19. Besides their application in the pandemic, research is being done for the potential use of such nucleic-acid based vaccines against cancer and HIV [5].

The Future of Vaccine Research

Looking back at how vaccines developed, we have come a long way in protecting people from deadly diseases. In 1980, the W.H.O. declared smallpox’s eradication, the complete removal of a disease from the human population. More diseases like malaria and polio may face the same fate in the future. We have even managed to create a vaccine against COVID-19 within a short period of time. As more vaccines become available and as more research is done, the containment or the eradication of certain deadly diseases is now a possibility, thanks to scientists like Dr. Jenner and Dr. Pasteur.

References:

[1] Fenner, F., Henderson, D. A., Arita, I., Jezek, Z., & Ladnyi, I. D. (1988). Smallpox and its Eradication. Geneva, Switzerland: World Health Organization. Retrieved from http://apps.who.int/iris/handle/10665/39485

[2] Riedel, S. (2005). Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center), 18(1), 21–25. doi:10.1080/08998280.2005.11928028

[3] Barranco, C. (2020, September 28). The first live attenuated vaccines.

Retrieved from https://www.nature.com/articles/d42859-020-00008-5

[4] Plotkin, S. (2014). History of vaccination. Proceedings of the National Academy of Sciences of the United States of America, 111(34), 12283–12287. doi:10.1073/pnas.1400472111

[5] Tahamtan, A., Charostad, J., Shokouh, S. J., & Mohammad, B. (2017, September). An Overview of History, Evolution, and Manufacturing of Various Generations of Vaccines. Journal of Archives in Military Medicine, 5(3), e12315. doi:10.5812/jamm.12315.