new ammunition in the fight against the escape of viral antibodies
The concept of a virus escaping from neutralizing antibodies seems intimately familiar in our post-COVID world—it’s the reason we wait in line for new iterations of vaccines while fearing the inevitable arrival of new viral variants that can evade those vaccines. It’s a stark reminder that while our immune systems, scientists and governments are fighting this virus, the virus is fighting back. In a recent preprint published at bioRxivTimothy Yu, graduate student in the lab dr. Jesse Bloom, and colleagues report efforts to predict virus escape from complex mixtures of neutralizing antibodies. In doing so, they hope to use cutting-edge experimental and computational techniques to stay ahead of the virus-human arms race, while potentially gaining new insight into how antibody mixtures interact with viral antigens at a fundamental level.
First, some vocabulary: antibodies are small proteins produced by our immune system whose task is to bind viral proteins, the so-called antigens (for example, the spike protein on the surface of SARS-CoV-2) i neutralize or prevent them from attacking our cells. To be more specific, any given antibody binds only a specific part of its corresponding antigen – this region is called epitope. We would like to imagine a simple scenario, where a viral infection causes your body to produce one type of antibody directed at a specific epitope, which the virus will slowly mutate to disrupt the binding of the antibody and avoid neutralization. However – as is usually the case in biology – the reality is more complex. A viral infection or immunization causes your body to produce a mixture of antibodies that recognize many different epitopes. Although this is thought to increase the durability of antiviral responses, we know from experience that viruses are still able to escape these ‘polyclonal’ antibody mixtures by accumulating mutations in multiple antigenic regions (multiple epitopes). Understanding how viruses manage this escape—and developing tools to predict when they will do so—is of paramount importance to public health and basic science.
There are methods for experimentally testing whether a viral variant can lead to escape from the antibody mixture, but they are relatively low-throughput and laborious, as each variant needs to be tested individually – a difficult task in situations where viral adaptation is rapid and many different variants occur in the population. Crucially, these methods also rely on prior knowledge of the mutations they produce, leaving us constantly ‘one step behind’ the virus we are trying to fight.
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