Breaking down the biology behind antibodies and COVID-19
In the past few weeks, there’s been a lot of media chatter about antibodies for COVID-19. For those interested in learning more, this post defines and explains common antibody terminology.
First, what are antibodies?
Antibodies are proteins generated and secreted by the immune system, specifically by a subset of immune cells called B cells. Antibodies have a Y-shaped structure and the arms bind to specific components on the surface of the virus to neutralize it. The binding is targeted because the antibodies recognize very specific sequences (of amino acids) and shapes (conformations) of the viral proteins (antigens). Antibody-mediated neutralization of virus stops the virus from infecting our cells, effectively stopping the virus from being able to replicate (make more of itself) and spread. Antibody binding to virus also flags it to help other cells in the immune system clear the virus. (A side note: antibodies and antibiotics are two completely different things, though they sound very similar).
Antibody structure. The grey portion binds very specifically to the antigen (in our case, virus protein) against which it was raised. Image source: genome.gov
How do antibody responses work and how long do they take?
B cells are a type of immune cell that produce antibodies. When a subset of B cells in our body see a piece of the virus they can bind and recognize, it triggers them to change. The process of generating strong and targeted antibody responses occurs in the time frame of weeks, rather than days, as B cells undergo a meticulous and controlled maturation processes in our spleen and lymph nodes. While they do this, other parts of the immune system work hard to control the infection by alternative mechanisms. Once B cells have completed the maturation process, they can generate an effective, targeted antibody response. This process also generates what we call memory B cells, which can quickly become activated in response to reinfection with the same virus in the future.
The timeline and magnitude of antibody responses following infection. Image source: Biology-forums.com
Are all antibody responses protective?
In short, no. Immune responses are controlled by many factors. Different infections elicit different levels of neutralizing antibody responses. Individual people also have differing antibody responses based on the makeup and current status of their immune system. The concentration and subtype of antibodies generated by the immune system, as well as the specific viral proteins that these antibodies target, also determine how protective the antibody response is. When infections do elicit protective antibody responses, the amount of time these responses persist is also variable (months vs. years vs. decades). While we often generate protective antibody responses, there are some scenarios when the antibody response can actually be detrimental. This is called antibody dependent enhancement (ADE) and has been observed in several scenarios (one example is dengue virus infection). It is difficult to know if a specific virus will elicit a protective antibody response until it can be thoroughly studied.
Factors that affect immune responses. Image source: From Aguirre-Gamboa et al. Cell Reports 2016 Nov 22; 17(9): 2474–2487
Can antibodies generated in response to one virus react to other related viruses?
In short, yes, but it depends. This concept is called cross-reactivity. For example, certain antibodies generated by SARS-CoV-2 infection can react to other coronaviruses if they bind to protein segments shared by both viruses. The genetic material of the virus needs to be similar for this to occur, though, so antibodies generated by infection with SARS-CoV-2 will not protect you from influenza, because flu is a different type of virus with unique genetic material and proteins compared to SARS-CoV-2. This is important for developing antibody testing approaches because we want tests that specifically detect antibodies generated by SARS-CoV-2 infection but do not detect antibodies to other coronaviruses associated with the common cold. Notably, these other human coronaviruses cause about 20-30% of common colds and are quite prevalent. Critically, all antibody tests need to be validated to be a trusted source of information about infection rate.
I hope this information is helpful for understanding these concepts and how they apply to the current situation at hand. Stay tuned for part 2 of “Breaking down the biology” where we’ll discuss antivirals and other therapeutics for COVID-19!
Stephanie Schell, PhD
Stephanie received her PhD in Virology and Immunology from the Penn State College of Medicine in 2019. For her PhD, she studied B cell and antibody responses induced after immunization and in the autoimmune disease, lupus. She is currently a postdoctoral scholar at the Penn State College of Medicine, working on several translational projects that focus on inflammatory skin diseases. When she isn’t in the lab, Stephanie enjoys being outside and competing in sports.