On March 16, 2020, the first volunteer received a shot of Moderna’s then-experimental Covid-19 vaccine, just 63 days after the company had generated a genetic blueprint of the new virus. But Moderna’s rival beat it to the marketplace: Pfizer’s Covid vaccine would be authorized for use in the United States less than a year later, a record-breaking achievement. Previously, the fastest a vaccine had ever been developed was for mumps—which took about four years.
The speed at which both companies were able to deliver their vaccines can be credited to mRNA technology. Instead of using the virus itself to spur an immune response, as older vaccines do, scientists instead spur it using a programmable piece of genetic code called mRNA. The mRNA tells the body to make a version of the coronavirus’s distinct spike protein, so it can make antibodies to neutralize that spike. The mRNA is quickly broken down, but the memory of the spike protein lingers in the immune system, so it’s ready to launch an attack if it encounters it again.
The promise of mRNA technology was its adaptability. Vaccine makers touted its plug-and-play nature. If the virus mutated to evade current vaccines, scientists could simply swap in a new piece of mRNA to match the new version of the virus. But today, despite waves of variants including Delta, Omicronand the latest threats—Omicron subvariants BA.4 and BA.5—the Covid-19 vaccines and booster shots still target the original virus that was identified in late 2019. Why haven’t variant-specific boosters arrived sooner?
“You’re working with a virus that is rapidly mutating. Each of these variants is around for a few months and then is replaced by a new variant,” says infectious disease specialist Archana Chatterjee, dean of the Chicago Medical School. “This is a race that we are continuously behind on.”
And BA.4 and BA.5 are the fastest movers yet. “This virus has, over the period of these two years, become more and more contagious,” continues Chatterjee, who is also a member of the Vaccines and Related Biological Products Advisory Committee (VRBPAC), an independent panel of experts that advises the US Food and Drug Administration.
While the currently available vaccines have greatly reduced death and hospitalization due to Covid-19, “their effectiveness does appear to wane with time,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, during a June 28 VRBPAC meeting. Initial booster shots helped restore some protection against severe disease, but their effectiveness also seems to fade.
In June, all of these factors led VRBPAC to recommend that vaccine manufacturers update Covid booster shots for fall and winter 2022, tailoring them to the BA.4 and BA.5 subvariants. Chatterjee says the committee made the recommendation based on evidence that these subvariants seem to be driving a new wave of hospitalizations across the US and the UK. The US government intends to buy millions of variant-specific doses for a fall booster campaign.
Jacqueline Miller, senior vice president of infectious diseases at Moderna, says the company recognized early on that they’d have to race to catch up with the virus. The first variants of concern—Alpha and Beta—were identified in late 2020, just as the vaccines were being rolled out. While the original vaccines held up against the Alpha variant, they were slightly less effective against Beta. “That was really what prompted us to go down this road of investigating variant vaccines,” she says.