Uncontrolled Spread: Why COVID-19 Crushed Us and How We Can Defeat the Next Pandemic

by Scott Gottlieb

The first two constructs used a strand of mRNA that would code for the production of the entire spike protein, while the other two would use mRNA that coded for just a specific region on the spike, called the receptor-binding domain or RBD. It was believed that the RBD would make the most attractive target for human antibodies. It was the exact point on the spike where that protein latched onto the ACE2 receptors lining our tissues. There were a lot of these ACE2 receptors in our lower airways, explaining why COVID targeted its victims’ lungs. Antibodies that target the RBD interfere with the spike protein’s ability to bind to these receptors, effectively blocking its capacity to enter our cells, and neutralizing its ability to infect.29 Of all the different regions on the long spike protein, it was the receptor-binding domain where our most potent, neutralizing antibodies would attach. Measuring the sheer volume of antibodies that COVID patients produced against their SARS-CoV-2 infections after they recover, about 90 percent targeted the RBD. So, a lot of a vaccine’s effectiveness would be driven by its ability to induce antibodies to that very specific binding region on the virus’s surface. The idea of using mRNA had never before found its way into a commercially available vaccine.