The makers of COVID-19 vaccines are figuring out how to tweak their recipes against worrisome virus mutations — and regulators are looking to flu as a blueprint if and when the shots need an update.

“It's not really something you can sort of flip a switch, do overnight,” cautioned Richard Webby, who directs a World Health Organization (WHO) flu center from St. Jude Children's Research Hospital.

Viruses mutate constantly and it takes just the right combination of particular mutations to escape vaccination. But studies are raising concern that first-generation COVID-19 vaccines don't work as well against a mutant that first emerged in South Africa as they do against other versions circulating around the world.

The good news: Many of the new COVID-19 vaccines are made with new, flexible technology that's easy to upgrade. What's harder: Deciding if the virus has mutated enough that it's time to modify vaccines — and what changes to make.

The WHO and the Food and Drug Administration (FDA) are looking to the global flu vaccine system in deciding how to handle similar decisions about COVID-19 shots.Influenza mutates much faster than the coronavirus, and flu shots have to be adjusted just about every year. National centers around the globe collect circulating flu viruses and track how they're evolving. They send samples to WHO-designated labs for more sophisticated “antigenic” testing to determine vaccine strength. The WHO and regulators then agree on the year's vaccine recipe and manufacturers get to work.For COVID-19 vaccines, Webby said a critical step is establishing a similar surveillance and testing network to flag the mutations that matter.Today, there's wide geographic variability in tracking and testing mutated versions. For example, Britain does more testing of the changing viral genome than the U.S.

Just because a variant is more contagious doesn't mean it also will be impervious to vaccination. But the variant first identified in South Africa is raising concerns. Columbia University's David Ho put blood samples from people given the Pfizer or Moderna vaccines into lab dishes with the mutated virus. Vaccine-produced antibodies still protected, but they were much less potent.Preliminary test results of two other vaccine candidates — from Novavax and Johnson & Johnson — soon backed up those findings. Both still protected but were weaker when tested in South Africa, where that variant dominates, than when tested elsewhere. A far smaller test of the AstraZeneca vaccine in South Africa has raised questions about its effect.“If the virus were able to make an additional mutation or two, it could escape even more,” Ho warned.

If fully immunized people start getting hospitalized with mutated virus, “that's when the line gets crossed,” said Dr. Paul Offit, a Children's Hospital of Philadelphia vaccine expert who advises the FDA.That hasn't happened yet, but “we should get ready,” he added.