Agreed. At the end of the day, their original sin was choosing the wrong conformation for their antigen at the design stage. A small but significant difference that makes their product that little bit less protective than their competitors. So, to keep up with the Joneses they play a little loose IMO with the numbers. The sad thing is that their vaccine is effective, just not quite as good as the others. That in itself is still an immensely valuable product, but the damage to their credibility (much of it the self-inflicted variety) is really problematic.With the first trial data, AZ also turned it into a PR-event by merging the main trial with one that had gone wrong but accidentally produced better protection. Back then, the real efficacy was 61% iirc, not the 70% they wanted the headlines to be. They have consistently oversold their product, both the efficacy and the output they're able to handle.
Scientists believe that for COVID-19 vaccines to be effective, our immune systems must develop antibodies that prevent this fusion. Such antibodies must target the spike protein in its aptly named prefusion conformation. Unfortunately for vaccine developers, spike proteins are liable to spring from their stubby prefusion shape into their elongated postfusion form on a hair trigger.
Fortuitously, Graham and a former postdoc, Jason McLellan, devised a solution to this problem before the pandemic. Through a bit of structural biology and persistent protein engineering, McLellan discovered that adding two prolines—the most rigid of the 20 amino acids—to a key joint of a vaccine’s spike protein could stabilize the structure’s prefusion shape. This 2P mutation worked in preclinical studies of Graham and Moderna’s MERS vaccine, so they applied it to Moderna’s COVID-19 vaccine.
Other companies, including Johnson & Johnson, Novavax, and Pfizer, are hoping the 2P mutation works for their COVID-19 vaccines too.
The 2P mutation might quite literally be the smallest detail that could make or break the first generation of COVID-19 vaccines. It’s an easy enough tweak to add during the early stages of vaccine design. And if successful, 2P-based vaccines may herald a new generation of vaccines whose molecular makeup is fine-tuned to craft a safer, stronger immune response.
Even if they are, the 2P mutation won’t be the only reason, and it might not even be the most important. One of the COVID-19 vaccine front-runners, produced by AstraZeneca, doesn’t even use it.
As for the production part, I would really love to read a deep dive into why it has been so tough to make their vaccine. Other companies have had their issues too, but AZ seems to really be struggling. I guess it could be lack of experience in the field.