The U.S. is still ramping up its vaccination program, hoping to finally clamp down on the COVID-19 pandemic. But even as vaccine doses are being rolled out, their makers are exploring several strategies to bolster them, hoping to protect people against worrying new variants that have sprung up in recent months, from South Africa to the U.K.

The companies that have FDA-authorized vaccines are currently working on the problem, out of concern that mutations in SARS-CoV-2 could make the virus more difficult to control. Several strains seem to spread more easily than older forms of the coronavirus. There are also concerns that some mutated versions could elude antibody responses that would normally protect people who have been immunized or previously infected.

Here's an overview of the approaches being pursued by Pfizer and its partner BioNTech and Moderna – the drugmakers with U.S.-authorized vaccines – along with Johnson & Johnson, whose vaccine is now poised for FDA authorization:

Booster shots of the existing vaccine: This approach relies on giving people who have already been vaccinated a follow-up dose of the same vaccine.

Pfizer and BioNTech calls for people who have already completed the normal two-dose regimen to get a third 30-microgram dose, 6-12 months later. Moderna's plan calls for a 50-microgram dose, after people have gone through its two-dose regimen.

Variant-specific booster shot: Much like how specific vaccines are tailored to fight influenza, drugmakers can craft a version of their vaccine to combat individual coronavirus variants. Moderna says its new vaccine candidate, based on the strain first identified in South Africa, is now ready for clinical testing. The company says it has shipped doses of that potential vaccine to the National Institutes of Health to get started.

Last month, Paul Stoffels, the chief scientific officer at Johnson & Johnson, said his company is also preparing a special version of its vaccine to target the spike protein found in the B.1.351 seen in South Africa.

A 'multivalent' booster: In this approach, drug companies essentially blend two versions of their vaccines into a single booster shot. One would target original or "ancestral" versions of SARS-CoV-2, while the other would go after new variants. Moderna says it will look at combining its original vaccine – known as mRNA-1273 – with the newer version it created to fight the B.1.351 coronavirus variant first identified in South Africa.

Putting the boosters front-and-center: As drugmakers tweak their original vaccines to respond more acutely to variants, they will also consider whether new versions of their vaccines might effectively replace the initial recipes. Moderna says it will explore whether its variant-specific booster and its multivalent booster should become the primary vaccination series of shots for people who haven't been exposed to the coronavirus.

In the future, different circumstances will likely determine which vaccine or booster a person receives.

Someone who has antibodies from a previous infection or immunization would probably only get a booster shot, for instance, while someone whose system hasn't been exposed to the coronavirus would receive "an updated vaccine that aims to provide immunity to both the ancestral strains and variants of concern," Moderna said on Thursday, during a call with investors.

It's also possible people could receive a vaccine that's tailored to variants that have been detected in their country.

Johnson & Johnson's new vaccine was found to be 66% effective at preventing moderate to severe cases of COVID-19 – a result that reflects testing in numerous countries, including South Africa and Brazil, where troubling new variants have emerged.

Current versions of their vaccines work against the new COVID-19 strains, Pfizer, Moderna and Johnson & Johnson say. Health experts also stress that all three of the vaccines are overwhelmingly effective in preventing the worst outcomes, such as hospitalizations and deaths. Still, newly tailored versions of the vaccines may be needed, as strains of SARS-CoV-2 continue to mutate and combine.

"While we have not seen any evidence that the circulating variants result in a loss of protection provided by our vaccine, we are taking multiple steps to act decisively and be ready in case a strain becomes resistant to the protection afforded by the vaccine," Pfizer CEO and Chairman Albert Bourla said in a statement about his company's plans to study boosters' effect on variants.

Pharmaceutical companies are studying boosters out of caution, Bourla added, to make sure they have an answer in the pipeline for an evolving coronavirus — and to ensure they have a path for emergency authorization if an updated vaccine or booster becomes necessary.

"This regulatory pathway is already established for other infectious diseases like influenza," said Ugur Sahin, CEO and co-founder of BioNTech.

Both Moderna and Pfizer/BioNTech created their vaccines using relatively new messenger RNA technology, which has been hailed for its ability to produce vaccine candidates quickly. That swift process, the drug makers say, can also help them produce new versions of their vaccines in response to coronavirus mutations.

Citing the speed and flexibility of mRNA, Moderna CEO Stéphane Bancel said on Thursday that his company "is committed to making as many updates to our vaccine as necessary until the pandemic is under control."

In contrast, Johnson & Johnson used a viral vector technique to make its vaccine, using the same strategy as the AstraZeneca / University of Oxford team. The approach is known to take longer than mRNA, but the resulting vaccine can also give patients immunity after a single dose.

Along with providing protection against new coronavirus variants, another potential benefit of booster shots, drug makers say, is that they can prolong or enhance protection even at smaller doses than the original regimen, easing some of the pressure on strained production and distribution networks.

Copyright NPR 2021.