A platform for developing rationally guided, broadly neutralizing antibodies for future pandemics, using SARS-CoV-2 as a model

The COVID-19 pandemic, which lasted for four years and caused millions of deaths worldwide, serves as a stark reminder of the consequences of inadequate pandemic preparedness. COVID-19 is caused by the SARS-CoV-2 virus, which mutates rapidly, making existing vaccines and treatments obsolete over time. Although the World Health Organization declared an end to COVID-19 as a global emergency in 2023, it would be unwise to assume this will be the last coronavirus to threaten us. Our research aims to develop mutation robust vaccines and antibodies that targets conserved regions of the viral spike protein-regions that do not change significantly even as the virus evolves. We have previously identified such conserved regions in the virus and rationally designed immunogens capable of neutralizing multiple variants. However, natural infections and mRNA vaccines do not seem to provide long-term protection against the virus. Our goal is to understand why and isolate broadly neutralizing antibodies from animals immunized with our immunogens. To realise this, we will isolate and study antibodies that specifically target the conserved regions of the virus, and test their ability to neutralize different variants in our pseudovirus and authentic virus assays. We will further assess how the antibodies counter new mutations, whether these mutations are naturally occurring or are artificially introduced in our pseudovirus platform. The study will investigate why some viral regions are harder to target and how mutations help the virus hide conserved regions from the immune system. This research will provide preemptive therapeutics, which can be predicted beforehand, and remain effective even as the virus evolves. By improving our understanding of viral mutation and escape from the immune system, we can design better vaccines and treatments for future viral outbreaks, ultimately strengthening global health preparedness.