Making virus-like vaccine particles in vitro

Viruses have evolved to do essentially one thing – protect their genes until they get them into the right host cells – and this, as we know all too well, they do with devastating success. In my talk I discuss how it is possible to synthesize infectious virus particles “from scratch”, i.e., from their purified genome and capsid protein components. I’ll also talk about how this same in vitro (“test tube”) synthesis can be used to make non-infectious virus-like particles containing genes in “messenger” RNA (mRNA) form that code for viral antigens. By functionalizing these particles to target professional antigen-presenting cells, they become vaccines that directly elicit a killer T-cell response. Alternatively, the particles can be used as scaffolds for presenting multiple copies of intact viral proteins – like the infamous “spikes” of SARS-2 – that will activate virus-specific B cells and the secretion of neutralizing antibodies. I compare our mRNA vaccine particles with the highly effective COVID-19 Moderna and Pfizer vaccines, and discuss the relative advantages and disadvantages of each, relating to the generation of antibodies and the proliferation of killer T cells. The differences arise from our form of mRNA being “self-replicating”, and from our delivery system involving monodisperse protein shells instead of polydisperse lipid nanoparticles.  Finally, I discuss how one can mimic the in vivo immune response to a vaccine by working – again in a test tube – with nothing more than (in vitro reconstituted vaccine particles and) purified antigen-presenting cells and killer T-cells.