With multiple COVID-19 vaccines authorized by the Food And Drug Administration (FDA) for emergency use, we should be basking in the sunlight of our progress. Unfortunately, it feels as though we are always one step behind this virus — constantly adapting our plans to combat an emerging issue. Now, new variants threaten to extend this pandemic and challenge the effectiveness of these vaccines. The key thing to realize is that these are not SARS-CoV-2 vaccines, they are COVID-19 vaccines. They are incredibly effective in stopping the disease of COVID-19 in people, but not necessarily at stopping the viral transmission of SARS-CoV-2 to others.
Understanding the partnership between transmission and variants is essential to our collective future. Viruses spread. It’s in their nature. They copy themselves, over and over, infecting as many people as possible. But with each copy, the virus has the potential to change ever so slightly — mutating into something different. This is called a variant. Unless we address transmission and stop the spread of SARS-CoV-2, we will continue to allow the development of new and potentially dangerous variants.
We must focus on stopping transmission.
The good news is that past outbreaks, such as polio, have provided us a road map. We know that to stop transmission, we need to address the three critical arms of the immune system: systemic immunity, T cell immunity and mucosal immunity. The best way to understand how our immune systems stop viral infection is to explain its three distinct parts.
Systemic immunity (serum neutralizing antibody)
Stopping transmission begins with immediately halting the virus’s effects on the body. That is to say, we must create systemic immunity to protect our lungs and blood system where viruses cause severe disease. Most vaccines authorized, or under development, around the world are focused on the activation of the Immunoglobulin G (IgG) antibody in the immune system. Of the five different types of COVID-19 vaccines reportedly being developed, most have one thing in common: they target IgG antibodies and T cell receptors. Whether it be through an mRNA, DNA or adenovirus-developed vaccine, they all circulate within the blood system and prime the systemic immune system to attack the coronavirus.
T cell immunity
The second step to stopping transmission is to ensure long-term individual immunity. This happens through T cells. They determine the level of immune response to foreign substances in the body. T cells play a critical role in clearing the already-started infection by targeting and destroying virus-infected cells. With this coronavirus, research has shown that these cells are needed for long-term protection from the virus to help fight reinfection. With numerous variants emerging around the world, and more possible to surface, reinfection is a very real possibility that we need to anticipate.
Mucosal immunity
Local mucosal immunity is the third and possibly most important step. Behind IgG, the second largest type of antibody is Immunoglobulin A (IgA), found in the linings of the respiratory tract and digestive system, as well as in saliva, tears and breast milk. These antibodies protect body surfaces that are exposed to outside foreign substances. This is critical when we’re fighting a highly contagious virus that spreads through respiratory droplets from coughing, sneezing and talking. Studies have shown that without mucosal immunity, the nasal cavity can serve as a reservoir for SARS-CoV-2. Unfortunately, this means that it is possible that recipients of intramuscular vaccines, while themselves protected from disease, could still contract an asymptomatic coronavirus infection and transmit it to others who may not be protected.
If we stop the virus at all of these checkpoints, we stop infection and we stop transmission. An unchecked virus, especially one as dangerous as this coronavirus, presents an escalating global threat. Each time we allow the virus to spread person-to-person, we risk mutation and the development of new variants. Until we have a safe and effective vaccine that can activate the three key areas of immunity, we have to remember that we are at risk of spreading the virus to others.
If we lose sight of transmission, we may very well perpetuate a cycle of treatment resistant variants, similar to the annual flu season.
For researchers, we need to stay vigilant and explore next-generation vaccines that can elicit immunity at all levels. We can still use science to stop the coronavirus in its tracks. For governments and policy makers, we need to apply the same level of urgency in ensuring researchers have the full support of our regulatory bodies and scientific administration to swiftly bring next-generation vaccines forward while keeping the public safe.
We face a virus like nothing we’ve seen before, but we have also applied a level of advanced science, public education and political priority against it. We very much have the opportunity to eradicate this virus, just like we have done with polio in the past.
M. Scott Harris, M.D., sits on the faculty of Georgetown University School of Medicine as an adjunct professor, where he directs a course on drug development under a grant from the NIH, and he is chief medical officer at Altimmune, Inc., a Maryland-based biotech company.