The US FDA has requested that COVID-19 vaccine manufacturers custom tailor their fall booster vaccines for the BA.4/BA.5 coronavirus strain, the agency announced Thursday.

The decision was made swiftly to offer vaccine manufacturers the chance to pivot from their current focus on the BA.1 strain, and adapt their products to the new strains.

The FDA requested clinical trials to begin on the new targeted vaccines against the new strains, but it was not clear if enough time was left to complete full evaluations of the new booster doses and their efficacies.

Dr. Peter Marks of the FDA said, “Vaccine manufacturers have already reported data from clinical trials with modified vaccines containing an Omicron BA.1 component and we have advised them that they should submit these data to the FDA for our evaluation prior to any potential authorization of a modified vaccine containing an omicron BA.4/5 component. Manufacturers will also be asked to begin clinical trials with modified vaccines containing an omicron BA.4/5 component, as these data will be of use as the pandemic further evolves.“

There is some debate, and ambiguity, over the new request. It is not clear if the fall booster should also contain components targeting the original strain of the virus, and it also did not specify if the new vaccine should primarily target the BA.1 Omicron strain, or the BA.4/BA.5 strains which comprise a majority of the cases seen in the US today.

Kanta Subbarao, chair of the World Health Organization’s Technical Advisory Group on COVID-19 Vaccine Composition, told the FDA that an Omicron targeting booster was necessary, but that the primary dose of the vaccine should still target the original strain despite its rarity today, presumably because it produces more severe disease.

The vaccine companies presenting data to the FDA lacked any data on head to head comparisons of vaccines targeting BA.1 vs the BA.4/BA.5 targeted vaccines. Some found that troubling.

Dr. Paul Offit, a voting member and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia (CHOP) said he found this concerning, and the FDA has not addressed those concerns. He had asked the head of Moderna, Stephen Hoge, if he had compared his original vaccine against the newer BA.4/BA.5 vaccines, and was told, “We are still collecting that data.”

Offit said of the new BA.4/BA.5 vaccines, “This is a new product, and I think as a new product it should be handled as a new product…we need a higher standard for protection than what we’re being given, I think it’s uncomfortably scant.”

Meanwhile, Dr. Cody Meissner, a voting member and chief of the division of pediatric infectious disease at Tufts Children’s Hospital, questioned if vaccines are even still necessary, given the new variants are not as deadly, and the vaccines no longer work as well as they did in the past.

Additionally, it is not even clear the variants being examined today will not have been replaced by entirely new variants by the fall.

Meissner said, “The question is will the strain mutate so that it’s resistant to the immunity that’s generated by the vaccine. It’s very hard to tell when that will happen.”

Dr. Céline Gounder, editor-at-large for public health at Kaiser Health News and an infectious disease specialist, said the lack of knowledge about the new subvariants and modelling of their spread, means it is not clear at all what level of protection current vaccines even offer.

She said, “We need to better model what fold increase is truly significant. Once you hit four-to-five fold, that’s a more significant increase, and may justify an update in the vaccine. But if it’s only a two-fold increase, in the antibody levels, that really doesn’t justify (boosters).”

The US Government has committed to acquiring 105 million additional doses of the vaccine, for all ages, for the fall season. The government retains an option to acquire an additional 195 million doses should the need arise, for a total cost of $3.2 billion. To date the government has spent $15 billion in total on Coronavirus vaccines from Pfizer/BioNTech, half the vaccine sales from the company. The US has set aside an additional $5 billion for boosters.