Last fall, when I asked my Clinical Microbiology students to name their favorite topic in the course, the top answer was “outbreaks”. I was not too surprised; examples of how the common cold spread and how Ebola epidemics begin helped to bring theoretical concepts about bacteria and viruses to life. A few months later, outbreaks became a common topic of conversation beyond the classroom. How to control a global outbreak (e.g. pandemic) is now our collective focus.
For a virus such as SARS-CoV-2 (aka COVID-19), which is highly contagious and can be deadly, preventing its spread is critical. This prevention depends on memory followed by action, in more ways than one. We practice prevention when we remember to wear a mask and maintain physical distance, and when we remember that staying home helps to slow down transmission.
Exposure, Response, and Vaccination
There is another type of memory that can protect us as well—when our white blood cells remember that a particular microbe is harmful and then act to remove it before it can cause disease. This type of memory (e.g. immunity) is carried out, in part, by B lymphocytes and T lymphocytes. B lymphocytes produce antibodies—proteins that specifically act against the invading pathogen. Although these cells are capable of responding to a pathogen upon first exposure (e.g. a primary immune response), the process of pathogen detection and immune response takes up to two weeks. Meanwhile, illness can develop and the pathogen can spread to others.
B and T lymphocytes also produce “memory cells” that remain in the body long-term. Because they are primed to respond to a particular pathogen, they will respond faster (within a few days) if the person is exposed a second time (e.g. a secondary immune response). This response can prevent the pathogen from causing disease. Immunity can develop through environmental exposure (which carries the risk of getting sick the first time) but can also be induced through vaccination (which has the intent of not causing illness). Many vaccines consist of a killed or weakened form of a pathogen. It retains identifying characteristics (or antigens) to trigger an immune response, such as surface proteins that are unique to that species or strain. Yet because it is weakened it will not harm the body.
Vaccination can therefore stimulate the production of memory cells, strengthening the immune system so it can respond quickly upon environmental exposure to the pathogen. Since SARS-CoV-2 is highly transmissible in humans and can cause illness, even death, developing a vaccine has become a priority of researchers around the world.
Vaccine Development for COVID-19
So what are the challenges of vaccine development, particularly against a novel virus such as SARS-CoV-2?
Effectiveness and safety: A vaccine must stimulate an immune response without causing adverse reactions. Identifying which molecular structures on a pathogen will trigger the strongest response is a process of (educated) trial and error. Some pathogens also evolve to no longer be recognized by the immune system (thereby evading the memory cells). Since SARS-CoV-2 has only recently emerged as a human pathogen, it will take time to identify the most effective molecules to target. If mutations occur within the virus over time that alter the structure of these molecules, this will reduce the effectiveness of an existing vaccine.
Time: Research and development typically takes years. Clinical trials on humans involve multiple phases whereby the safety and effectiveness are tested, first in small groups and then expanding to thousands of people. Many vaccines fail to pass the trials, which means multiple candidate vaccines must be developed against a single pathogen. This process can take 4-10 years but can be shortened if candidates are developed simultaneously. There are currently eight candidate vaccines for COVID-19 in clinical trials, and 100 more in pre-clinical trials. With this concerted effort, researchers predict a vaccine could be ready in 12-18 months, although data on the long-term safety and widespread effectiveness of such a vaccine would not be known yet.
Money: Not surprisingly, the equipment, expertise, and time required to develop an effective vaccine is expensive. When the cost of the failed candidates vaccines is factored in, producing a successful candidate that passes through clinical trials can cost as much as $500 million, according to one study.
Developing a vaccine to combat any novel pathogen, including SARS-CoV-2, can prove critical for controlling the spread of disease. Vaccines help the immune system to develop memory of a pathogen without causing disease, thereby strengthening its response to an actual infection. Despite the challenges of developing an effective vaccine in a short amount of time, this is the collective goal of researchers to combat COVID-19, so that we can reduce the spread of such a formidable pathogen.