ImmunologyVaccination

Jenner’s Legacy, Part 1: How Smallpox Was Eradicated with Vaccination

Published online Jan 4, 2017

Kaval Kaur

Research Fellow

Singapore Immunology Network

The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

Over 200 years ago, smallpox was devastating humankind — 20 to 60 per cent of infections were fatal and those who survived were plagued with disfiguring scars and often went blind.  The deadly disease was feared by everyone except milkmaids, who intriguingly were immune.  An English physician and scientist, Edward Jenner, observed that milkmaids had blisters caused by cowpox, a disease similar to smallpox but much less dangerous, and hypothesized that having cowpox protected these milkmaids from smallpox.  In 1796, he went on to test this experimentally.  He took pus from the fresh cowpox blisters of a milkmaid and inoculated an 8-year-old boy — while it may be disconcerting from a modern viewpoint, inoculation was a standard medical practice at that time. Weeks later, Jenner inoculated the boy again, this time with pus from fresh smallpox blisters.  The boy did not contract smallpox and it was concluded that he was protected from the deadly disease.

This simple, yet incredibly significant, piece of evidence went on to lay the foundations of vaccination and revolutionize modern immunology.  Scientists quickly realized that Jenner’s strategy of vaccination — inoculating a person with a less dangerous version of the disease-causing agent to provide future protection against the disease — was a powerful tool to tackle a host (no pun intended) of infectious diseases.  Over the years, the crowning glories of immunology have been the successes of vaccines as diseases such as smallpox, Rinderpest, and wild polio type 2 have been eradicated, while many others such as measles, mumps, rubella, tetanus and diphtheria have been significantly controlled and are on the road to elimination.

While Jenner’s strategy of vaccination has been successfully validated time and time again over the past two centuries, it is only in recent years that scientists have determined how vaccination actually works.  When vaccines containing dead or weakened disease-causing agents — such as viruses or bacteria — are injected into the body, they prime the immune system to react, but do not actually trigger the disease.  Cells of the immune system recognize the vaccine components as foreign and launch an immune response, reacting as if it was a real attack.  Antibodies are produced, and activated immune cells go on to populate the long-term memory compartments of the immune system.  If the body encounters the same disease-causing agent in the future, pre-existing antibodies will neutralize it while memory cells will react rapidly to clear the invader before it can gain a foothold and cause disease.  The ability of vaccines to harness the power of immunological memory and provide future protection against disease gave the scientific community confidence that we had capacity to fight against all infectious diseases.

Unfortunately, as scientists began applying Jenner’s methodology of smallpox vaccination to other infectious diseases, it became clear that his strategy was not a ‘one-size-fits-all’ approach.  Numerous diseases present challenges that make developing highly effective vaccines, with the dead or weakened versions of the disease-causing agent, very difficult.  Influenza and dengue, are excellent examples of such diseases — both are caused by complex viruses and the body’s natural immune response to them makes Jenner’s straightforward approach to vaccination fall short. 

Stay tuned for Part 2 of Jenner’s Legacy, in which I will discuss the challenges in developing vaccines for Influenza and dengue.

Dr. Kaval Kaur is a research fellow in Katja Fink’s laboratory at the Singapore Immunology Network. She was awarded the NSS-PhD scholarship to study immunology at the University of Chicago. She enjoys many different topics within immunology, but it is the interplay between viruses and the immune system that has always captivated her. Her research interests include the role of B cells and antibodies in the fight against the many viruses that invade us and investigating how we can manipulate the responses of the immune system for vaccine development. For her graduate studies, she focused on influenza and now, at SIgN, she has turned her attention to dengue.