New ammunition in combating viral antibody escape







The concept of viral escaping from neutralizing antibodies seems intimately familiar in the post-COVID world—it’s why we wait in line for new iterations of vaccines while dreading 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 fight this virus, the virus is fighting back. In a recently published preliminary edition to bioRxivTimothy Yu, graduate student in the lab Dr. Jesse Blumand colleagues reported efforts to predict viral escape from complex mixtures of neutralizing antibodies. In doing so, they hope to take advantage of the latest experimental and computational technology to stay ahead in the virus-human arms race, while potentially gaining new insight into how mixtures of antibodies interact with viral antigens at a fundamental level.

First, some vocabulary: Antibodies They are small proteins produced by our immune system that bind to so-called viral proteins antigens (for example, the spike protein on the surface of the SARS-CoV-2 virus) f invalidate or stop them from invading our cells. To get more specific, any given antibody only binds to a specific part of the corresponding antigen – this is called a region epitope. We like to imagine a simple scenario, where a viral infection causes your body to produce one 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 complex. A viral infection or immunization causes your body to produce a mixture of antibodies that recognize many different epitopes. While this is thought to increase the robustness of antiviral responses, we know from experience that viruses are still able to 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 it will occur — is of paramount importance in public health and basic science.

Methods exist for experimentally testing whether a viral variant can trigger escape from antibody mixtures, but they are relatively low-throughput and cumbersome, as each variant needs to be tested individually—a tall order in situations where viral adaptation is rapid, and many variations Variables arise in the population. Crucially, these methods also rely on prior knowledge of the mutations that are produced, constantly leaving us “one step behind” the virus we’re trying to combat.

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