What are the rules for building a vaccine? A nano-architect tries to avoid making carbuncles.

In the UK, all discussion of new building happens under the distant gaze of Prince Charles. He famously gave a speech saying that he “would understand better this type of high-tech approach if you demolished the whole of Trafalgar Square and started again with a single architect responsible for the entire layout, but what is proposed is like a monstrous carbuncle on the face of a much-loved and elegant friend.” As nano-architects in our group, we also must have some ideas on balancing effectiveness and elegance. Molecular design has particular importance when we try to build nanoparticles as vaccines for infectious diseases or to drive anti-cancer immune response. But who knows the rules? In the recent review that I wrote with Rory Hills in Current Opinion in Biotechnology (also free on PubMed Central), we try to identify the latest insights in this area. Virus-like particles against infectious disease and cancer: guidance for the nano-architect. Hills RA, Howarth M. Current Opinion in Biotechnology. 2021 Oct 29;73:346-354. This review brings together major advances in the last 2 years, such as the use of DNA origami to organise antigens with nanometre precision. We also highlight new coupling approaches to decorate virus-like particles and to pack inside immune stimulants. Patchwork or mosaic particles have shown exciting potential to give immune responses that protect across different virus variants. For cancer, the virus-like particle is itself often the adjuvant. Notably in this period there have also been landmark clinical trials using virus-like particles for the SARS-CoV-2 pandemic and malaria. Is there any advance or principle that we missed? What do you think counts as a carbuncle at the nanoscale?

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