The viral escape concept of antibody neutralization seems intimately familiar in our post-COVID world: it’s why we wait in line for new iterations of vaccines while fearing the inevitable arrival of new viral variants that can evade those vaccines. It is a stark reminder that as our immune systems, scientists, and governments fight this virus, the virus is fighting back. In a recent preprint published in bioRxiv, Timothy Yu, a graduate student in the laboratory of Dr. Jesse Bloom, and colleagues report on efforts to predict viral escape from complex mixtures of neutralizing antibodies. In doing so, they hope to take advantage of state-of-the-art computational and experimental techniques to stay ahead of the arms race between virus and man, while gaining new insights into how antibody mixtures interact with viral antigens at a fundamental level. .
First, a bit of vocabulary: antibodies are small proteins produced by our immune system whose job it is to bind viral proteins called antigens (for example, the spike protein on the surface of SARS-CoV-2) and neutralize or prevent them from invading our cells. To be more specific, any given antibody only binds to a specific portion of its corresponding antigen; this region is called epitope. We’d like to imagine a simple scenario, where a viral infection causes your body to produce a single type of antibody targeting a specific epitope, which the virus will slowly mutate to disrupt antibody binding and escape neutralization. However, as is often the case in biology, the reality is more complicated. Viral infection or immunization causes your body to produce a mixture of antibodies that recognize many different epitopes. While this is believed to increase the durability of antiviral responses, we know from experience that viruses can still escape these ‘polyclonal’ mixtures of antibodies by accumulating mutations in multiple antigenic regions (multiple epitopes). Understanding how viruses manage this escape, and developing tools to predict when they will, is of paramount importance to public health and basic science.
Methods exist to experimentally test whether a viral variant can cause escape from antibody mixtures, but they are relatively low-throughput and laborious, as each variant must be tested individually, a difficult task in situations where viral adaptation is rapid and rapid. many different. Variants arise in the population. Crucially, these methods also rely on prior knowledge of the mutations that occur, constantly leaving us “one step behind” the virus we are trying to combat.
Source: news.google.com