McLellan and his colleagues used standard techniques to create a MERS vaccine, but they ended up with many post-fusion spikes, which were useless for their purpose. Then they discovered a way to leave the protein fixed in the prefusion form, when it looks like a tulip. All they had to do was swap two of more than 1,000 protein components for a compound called proline.
The resulting spike – named 2P, for the two new proline molecules it contained – was much more likely to take the desired tulip shape. The researchers injected the 2P spikes into mice and they found that the animals could easily fight the infections caused by the MERS coronavirus.
The team submitted the documentation to patent their modified tenon, but the world hardly noticed the invention. MERS, although deadly, is not highly contagious and proved to be a relatively minor threat; fewer than 1,000 people have died from MERS since it first appeared in humans.
However, at the end of 2019, a new coronavirus emerged, SARS-CoV-2, which began to plague the world. McLellan and his colleagues jumped into action, designing a special 2P spike for SARS-CoV-2. Within days, Moderna used that information to design a vaccine for COVID-19; it contained a generic molecule called RNA with the instructions to create the 2P spike.
Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and beginning clinical trials. All three vaccines that have been licensed in the United States so far – from Johnson & Johnson, Moderna and Pfizer-BioNTech – use the 2P spike.
Other vaccine manufacturers are also using it. Novavax has had strong results with the 2P spike in clinical trials and is expected to seek authorization for its emergency use from the Food and Drug Administration in the coming weeks. Sanofi it is also testing a vaccine with spike 2P and hopes to finish clinical trials later this year.
Two prolines are good; six are better
McLellan’s ability to find life-saving clues in the structure of proteins has earned him deep admiration in the world of vaccines. “This guy is a genius,” said Harry Kleanthous, a program manager at the Bill & Melinda Gates Foundation. “You should be proud of this immense achievement that you gave to humanity.”