Moderna, Pfizer ready multi-pronged plans for coronavirus variants

Thursday, February 25, 2021

Source: BioPharma Dive

Dive Brief:

  • Moderna and Pfizer are progressing plans to test additional booster shots or modified vaccines tailored to a coronavirus variant originally detected in South Africa, the companies said in separate announcements Wednesday and Thursday.  
  • The variant-specific booster will undergo clinical testing at the NIH and in studies run by Moderna. The biotech also will evaluate a lower-dose booster of its original coronavirus vaccine and a separate product that combines the traits of both shots. In parallel, Moderna is taking steps to boost its manufacturing capacity for next year.
  • Researchers aren't certain whether the so-called B.1.351 variant reduces the efficacy of Moderna's vaccine, but laboratory tests have shown the immune response to infection is lower than against the original strain. The company is advancing these booster strategies "out of an abundance of caution," a plan encouraged by regulators in the U.S.

Dive Insight:

Vaccine developers are urgently trying to meet demand for the first generation of coronavirus shots, while simultaneously preparing to adapt them in response to a mutating virus.

Both are equally vital missions. Few countries have immunized more than a small fraction of their populations, even as the fast spread of more infectious strains increase the urgency of those vaccination campaigns.

In order to gauge the threat these variants pose, researchers have exposed blood drawn from vaccinated volunteers to engineered versions of the coronavirus that share mutations found in B.1.351 and other strains.Testing of both Moderna’s and Pfizer’s vaccines showed fewer antibodies were produced against B.1.351 than were generated against the original strain that spread from China a year ago.

While both developers believe the antibody levels to B.1.351 are still protective against COVID-19, the results raise some questions about how well the strong efficacy of the company's vaccine will hold up and how long immunity will last.  

"At some point, you’d expect...immunity to wane" given that’s what’s seen with other coronaviruses, said Moderna president Stephen Hoge, on a conference call with analysts. 

More worrisome were recent study results that showed Johnson and Johnson's experimental vaccine appeared less protective against moderate or severe COVID-19 in South Africa, where nearly all the study volunteers who became ill were infected with B.1.351. J&J's vaccine still offered strong protection against severe COVID-19, however.

South Africa's government, meanwhile, has stopped use of a shot developed by AstraZeneca and the University of Oxford due to disappointing effectiveness against the variant there.

In Moderna’s case, Hoge said the company is preparing boosters to cover what may happen in the future, such as more virulent strains, seasonal recurrence, and any possible "gaps in immunity" that result.  

"None of us want to be in a situation where we wait until there are re-infections and increased morbidity and, God forbid, more mortality in a seasonal epidemic," Hoge said, "and then say ok now it’s time to start boosting people."

With its plan, Moderna appears to be covering all of its bases, seeking to identify the best dosing strategy out of three options: a booster of the original vaccine, adding a variant-specific booster or adding a combined booster known as a "bivalent" vaccine. Moderna will use a 50 microgram or lower dose for all three options, smaller than the 100 micrograms used for both doses in its current vaccine regimen.

With the B.1.351-specific booster now in the hands of NIH scientists, and a trial of a three-dose regimen now underway, Moderna could have an answer in a few months.

Pfizer and partner BioNTech, meanwhile, are starting out by offering participants in its Phase 1 clinical trial in the U.S. a booster shot of its original vaccine six or 12 months after they were fully immunized. The study will test up to 144 participants, split into younger and older groups, and assess their ability to neutralize coronavirus "strains of interest" one week and one month after a booster. 

Separately, the partners are discussing the design of a study of a B.1.351.-specific-booster with regulators in the U.S. and Europe.  

"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," said Pfizer chairman and CEO Albert Bourla, in a statement. 

The Food and Drug Administration this week released guidelines on developing variant-specific versions of already authorized vaccines, indicating modified boosters could gain clearance based on "immunogenicity" studies in a few hundred patients. The approach shares some similarities to how seasonal influenza vaccines are adapted each year.

But producing new boosters would draw on developers' production lines, which are already tested by overwhelming global demand for doses. Also on Wednesday, Moderna said it is working to build more manufacturing capacity for 2022, and upped the "floor" of its production estimate this year to 700 million doses.

The new investment would bring total 2022 capacity to a minimum of 1.4 billion doses, the company said, assuming a 100 microgram dose. As the booster shots now being tested will use a 50 microgram dose, there is potential for greater output, depending on which strategy Moderna chooses.

View All News »