COVID-19 HAS effectively ground modern society to a halt. The virus has claimed countless lives, stressed the healthcare capabilities of many countries to their breaking point, and forced millions of people into effective social isolation in order to avoid further infections. As the consequences of the global outbreak continue to grow, a concerted effort is being undertaken to develop a potential vaccine for COVID-19. However, most experts seem to agree that any potentially effective vaccine is more than a year away from completion. So, what makes vaccine development such a lengthy and difficult process, and why should creating one still be a top priority for the international community?
Origin of vaccines
The British physician, Edward Jenner is considered the father of vaccinology for devising a well-defined procedure for developing vaccines*. During one of his trips, Jenner had visited a small town which was regularly beset by smallpox and discovered that milkmaids who had previously suffered from cowpox did not contract smallpox. Based on this observation, Jenner injected a diluted form of the cowpox virus to an eight-year-old boy named James Philips in 1796. Though Philips developed mild symptoms from the inoculation, he soon recovered and later became immune to smallpox. Based on his discovery of the correlation between cowpox and smallpox, Jenner later tested his method on 23 additional subjects and published his findings in his 1798 paper**. Jenner was not the first person to recognize that cowpox conferred immunity to smallpox, but he was the first to study the effect from a scientific perspective, an effort which has served as the foundation for modern vaccinology.
The developmental process of vaccines
The Centers for Disease Control and Prevention (CDC) divides the developmental cycle for a new vaccine into six stages: the exploratory stage, pre-clinical stage, clinical development, regulatory review and approval, manufacturing, and quality control***. In the exploratory stage, a vaccine developer researches a natural or synthetic material that could be used to create a new vaccine. Then, in the pre-clinical stage, researchers test whether the candidate vaccine shows immunity to a target disease using animal testing and other relevant methods. This is followed by a meticulous, three-phase testing process in clinical development. In each phase, the number of test participants is exponentially increased to confirm the vaccine’s safety and effectiveness across a wide range of users. Once this is complete and the vaccine has been approved by the given nation’s regulatory body such as the U.S. Food and Drug Administration (FDA) or Korea’s Ministry of Food and Drug Safety, drug manufacturers can begin releasing the new vaccine.
How does a vaccine work?
When a new pathogen enters the body, B cells and helper T cells of lymphocyte function to develop an appropriate immune response***. B cells are triggered to begin producing antibodies that can recognize and lock onto the foreign substance. Once these antibodies are produced, they allow T cells to find and destroy the threat. In addition, these antibodies stay in the body providing an adaptive immunity to future infections by the same pathogen. This is where vaccines come in. Liu Chang-seung (Prof., Dept. of Medicine) explained that “If we create an immunological memory of a certain pathogen prior to its invasion using vaccines, our immune system can respond immediately to its unexpected invasion.” What’s more, vaccines do not just speed up the production of antibodies; they can also make up for potential flaws in the body’s immune response. Liu said that this is because “Adaptive immunity works in a similar fashion to recollecting people’s names. Similar to how we cannot and do not have to remember every person we meet, our immunological memory also gets blurry and even malfunctions.”
What do vaccines share in common?
Not all vaccines are the same. An attenuated vaccine is a weakened live pathogen whereas inactive vaccines are those in which the pathogen has already died. A third type, referred to as a subunit vaccine, is made from an antigen, the part of a pathogen which triggers the immune response****. By isolating specific parts of antigens, subunit vaccines can prompt an immune response that is more attuned to individual diseases. Here Liu added, “Scientists have now devised a way to produce antigens without having to use the entire pathogen. We can now extract and mass-produce them safely through genetic recombination.”
Although vaccines can vary in forms, the basic premise is that a substance used in creating a vaccine must first be weakened or rendered inactive in order to prevent actual infection. There are pros and cons to either approach. A dead pathogen often fails to create lasting immunity, as it does not provide a clear clue for our immune system to recognize. Conversely, attenuated vaccines can be harmful to people with weaker immune systems so more care must be taken in developing one. Although attenuated vaccines are difficult to make, they are crucial, as some pathogens react to the immune system only in their live forms.
Vaccine for a virus
Every vaccine must provide a clear evidence for our immune system to recognize the pathogen, namely the target antigen. Although any part of a pathogen can serve as the target antigen, it must be easily identifiable so that our immune system can distinguish it from other cells.
Finding a target antigen is the key to developing a new vaccine. However, finding a common target antigen that is not prone to genetic mutation is easier said than done. The genetic mutation of a virus is a momentous factor that limits the effectiveness of a vaccine. Viruses are more vulnerable to genetic mutation than bacteria as they have no cell walls. When a mutation occurs in the target antigen of a vaccine, the old vaccine may no longer work. As the target antigens of RNA viruses like COVID-19 and influenza are especially prone to such mutations, vaccines for these types of disease must be updated regularly. Think of how we are advised to get a routine vaccine injection for seasonal influenza.
Liu says finding a common target antigen in viruses and their mutated forms can lead to the advent of a powerful vaccine. “Smallpox, hepatitis, and Japanese B encephalitis viruses are known to have perfect vaccines, and their vaccines all have a [strong] target antigen in common.” Even though every virus has a mutative property, unless said mutation completely changes the property of a virus, vaccines can still work. Also, contrary to the popular belief, it is a generalization to state that vaccines for virus are more difficult to develop than those for bacteria; tuberculosis has one of the highest prevalence rates in the world despite being bacterial. “In the end, a vaccine’s preventive effectiveness is determined by the unique properties of each pathogen, not by the type of pathogen,” said Liu.
Can we expect a vaccine for COVID-19?
Vaccine development can take years and the development costs can be astronomical. As many countries are conservative in their willingness to develop one, vaccines tend to be underprovided. In light of this, U.S. epidemic expert Anthony Fauci’s optimistic view that a COVID-19 vaccine can be prepared within 18 months, has been met with skepticism by a number of health experts*****. They emphasized that vaccine development cannot be rushed as expediting the clinical development phase potentially endangers public safety.
A COVID-19 vaccine is an uncertain proposition. Unlike the influenza virus which already has an established vaccine platform, COVID-19 is still novel and has not been fully identified. The lack of past data makes it difficult to anticipate what could serve as an effective target antigen. Liu said, “A COVID-19 vaccine will take longer than expected to develop, so it will be difficult to cope with current pandemic using vaccines. However, as many experts expect COVID-19 based mutations to keep appearing in the near future, [developing a vaccine] is important for establishing a vaccine platform for all coronaviruses.”
*The Jenner Museum
**Jenner’s 1798 paper is titled, Inquiry into the Cause and Effects of the Variolae Vaccine, A disease Discovered in Some of the Western Countries of England.
****U.S. Department of Health & Human Services