Vaccine Development: A Brief History
In this piece, we take a look at the evolution of vaccines over time, accomplishments in disease eradication, and the different types of vaccines.
Introduction
Infectious diseases are a fact of life, much like death and taxes. The first recorded pandemic occurred in 430 B.C.E in Athens, Greece, killing an estimated two-thirds of the population. Later, an outbreak of what is now thought to have been smallpox decimated the Roman Empire in the 165 C.E. Antonine Plague and lasted fifteen years, spread by soldiers returning from war in the East. Thanks to advances in modern medicine, our modern-day outbreaks are short-lived and much less severe. The development of vaccines has protected us from some of the most contagious diseases, including smallpox, polio, and measles, and has averted an estimated 154 million deaths.
However, as innovations in vaccines continue to expand the range of diseases we can prevent, recent rises in vaccine hesitancy have begun to threaten the efficacy of vaccination efforts. vaccine hesitancy has started to grow. Vaccine misinformation takes advantage of gaps in scientific education, from the different types of vaccines to the history of successfully eradicated diseases. In this piece, we aim to give you a historical perspective on vaccine development, taking you through the development of the first recorded vaccine and total eradication of a disease to present-day mRNA vaccines that slowed the spread of the COVID-19 pandemic.
1796 to Today - Vaccines Through Time
In the 1700s, a lethal virus known as smallpox raged across the world, causing pus-filled rashes all over the body, leaving victims with life-long and potentially lethal complications such as encephalitis, arthritis, or sepsis. In the midst of this epidemic, Edward Jenner, an English physician, noticed that milkmaids were often more resistant to smallpox. He hypothesized that this resistance was due to their close proximity to cows and subsequent exposure to cowpox, a weaker relative of smallpox. To test this theory, Jenner took a sample of a milkmaid’s cowpox blister and inoculated an 8 year old boy, James Phipps. Young James felt sick for a few days but recovered from cowpox, and a couple months later, Edward Jenner inoculated the boy with smallpox to test his resistance. Shockingly, the boy did not develop smallpox, marking the first published successful human vaccination against smallpox.
Since the development of the smallpox vaccine, this highly contagious and deadly disease has been eradicated, thanks in large part to robust vaccination and global public health efforts. Through global disease surveillance, outbreaks of smallpox were able to be controlled by a method known as ring vaccination, which consists of isolating diagnosed patients and quickly vaccinating all of their close contacts to prevent further spread. These dedicated efforts led to the complete elimination of this severe disease, a major accomplishment following millenia of unrelenting and devastating smallpox outbreaks.
In the modern age, infectious disease and epidemiology research have given rise to several forms of vaccines that can utilize small proteins, a bit of RNA, or a weakened virus to build immunity to disease. When designing vaccines, scientists must take into consideration how the immune system “sees” the pathogen in order to figure out the best way of training the immune system to fight it. One type of vaccine you might be familiar with is what’s referred to as a live attenuated or an inactivated vaccine, where the pathogen is either significantly weakened or killed before immunization. One well-known example of this kind of vaccine is the polio vaccine.
In the mid-20th century, poliovirus caused a horrible epidemic and left countless individuals - mostly children - paralyzed after the virus infected their nervous system. Over time, two vaccines emerged to combat the spread of this disease. The first, the inactivated polio vaccine (IPV), was created by Dr. Jonas Salk in 1955 and is composed of poliovirus which has been killed through heat, enzymes, or removal of viral material necessary for replication. Six years later, the oral polio vaccine (OPV) was created by Dr. Albert Sabin, which was a live attenuated vaccine consisting of liquid drops containing up to three types of weakened poliovirus strains.
These two vaccines greatly aided the Global Polio Eradication Initiative, which was composed of several organizations and national governments, including the U.S Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and UNICEF. During this initiative, however, the live attenuated oral polio vaccine gave rise to some incidents of vaccine-derived polio, predominantly in immunocompromised individuals. Upon realizing this, the United States switched to using the inactivated form of the vaccine in 2000, eliminating the risk of vaccine-derived polio. Because of the polio vaccines, it is estimated that 20 million people have been spared from the paralytic effects of polio, with 1.5 million deaths prevented. Had it not been for vaccines, these diseases would still currently affect us, leading to innumerable severe infections and significant societal and economic burdens.
While vaccination with a whole virus can give the immune system a leg up in creating protective antibodies against many different viral proteins, this is not necessarily the best solution for all viruses. Because viruses have many different ways of infecting, replicating, and evading immune detection, one kind of vaccine may not work for every type of virus. Additionally, scientists must consider the application of the vaccine. Live attenuated vaccines require cold storage—meaning that they cannot be transported very well, for example—as well as the cost to produce different kinds of vaccines. Depending on the pathogen or outbreak severity, vaccines must be tailored to elicit the strongest immune response and offer the best protection possible.
In some cases, it can be enough to vaccinate with a single kind of viral protein in order to induce a protective immune response. For example, the vaccine against human papillomavirus (HPV), a virus which is estimated to currently infect an estimated 42 million Americans, contains surface proteins from the 9 most common types of HPV. This vaccine, known as Gardasil-9, exposes the immune system to these surface proteins, allowing for the production of antibodies that will recognize and lead to the destruction of HPV. Vaccination against HPV offers protection against disease caused by the virus, which often includes cancer of the vagina, penis, anus, or throat. HPV alone is responsible for 36,000 cancer cases each year, exemplifying the importance and necessity for this vaccine when it comes to preventing virus-induced cancer.
The newest kind of vaccine technology involves messenger RNA (mRNA) encoding one piece of a viral protein, largely popularized by the Pfizer and Moderna SARS-CoV-2 vaccines. Though the COVID-19 pandemic marked the start of widespread usage of this vaccination platform, studies into mRNA vaccines have been ongoing for decades. In the 1990’s and early 2000’s, several groups began demonstrating that, by introducing mRNA encoding for a specific protein (viral or cancer antigens), cells can be primed to recognize and destroy a virus or cancerous cell.
One of the largest barriers to mRNA vaccine development was figuring out how to deliver the mRNA directly into cells, where the cell could use the mRNA template to make the small piece of antigen that would prime the immune system against the pathogen. Free-floating mRNA in the body is quickly destroyed, as it cannot pass through the cell membrane on its own. However, by enclosing the mRNA in lipids—the same molecules your cell membrane is made of—the mRNA molecule can enter the cell. This lipid nanoparticle (LNP) system simply refers to a small particle or ball of lipids that protects the mRNA from degradation in the body. Since the start of the pandemic, hundreds of millions of people in the United States and across the world have received the mRNA vaccine, helping slow the spread of the virus and the harmful–and, potentially deadly–health effects of SARS-CoV-2.
Conclusion
From variolation in ancient Asia and Africa—a practice where dried smallpox scabs or pus was inoculated into a healthy individual to protect against disease—to modern vaccination techniques, disease has been repeatedly and successfully fought by exposing the immune system to small doses of infectious material. With today’s modern scientific knowledge and technology, vaccine development is significantly more efficient and effective.
New threats, however, are on the rise. We are currently living in an age of both a rapidly expanding human population and an increased geographical spread of diseases, with a warming climate expanding the territory of disease vectors, such as mosquitoes. Viruses that once only circulated in tropical areas are pushing further north, leading to new possibilities for human infection and spread.
To combat this increase in disease, we must focus our efforts on developing treatments and preventative measures. However, recent challenges to infectious disease research pose an obstacle when it comes to staying ahead of disease outbreaks. Through cuts for research funding, censorship of our leading experts, and cancellation of important viral surveillance programs, it is unclear whether we will have the resources necessary to quickly respond to the next outbreaks. One thing is for sure—there will be more epidemics.