With regard to coronavirus variants emerging around the world, the U.S. Food and Drug Administration is figuring out how to quickly review the adaptation of vaccines that better protect against mutants – and the regulatory agency is turning to its experience with annual flu shots to do it.
The regulatory agency said in a statement late Thursday that it was actively seeking out what kind of “streamlined” manufacturers of authorized COVID-19 vaccines could submit. The agency expects to have a draft of its guidance within the next few weeks.
The announcement indicates that manufacturers of authorized vaccines will not be required to submit data from large, months-long clinical trials, just as they did for their initial authorization. Data on any modified vaccine – even if completed – will still need to be sufficient to convince FDA scientists that a next-generation shot is safe and effective against variants. Vaccine adaptation may include changes to the initial vaccine design or addition of new vaccine components, the FDA said.
So far, the FDA has issued emergency use permits for two COVID-19 vaccines, one mRNA-based vaccine made by Moderna and another by partners Pfizer and BioNTech. (The FDA is now reviewing an EUA application for a third candidate, made by Johnson & Johnson, which is a non-repeating adenovirus-based vaccine.) Both mRNA vaccines have shown approximately 95 percent efficacy in massive international phase III trials. However, these trials were conducted before the emergence of variants, some of which apparently evade immune responses. Early clinical data indeed suggest that the efficacy of the vaccine will be reduced by the emerging variants, although it will not be completely eliminated.
The FDA emphasized this last point, writing: ‘To be clear, as we continue to develop an understanding of and address any impact of variants on FDA-regulated products, the information available at this time indicates that the authorized vaccines remain effective to the American public against the current circles of COVID-19. ”
“We have to prepare”
But it is also clear that the pandemic coronavirus, SARS-CoV-2, continues to evolve, becomes more transmissible and can evade immune responses. We will probably continue to see variants emerge. “We need to prepare for all opportunities,” FDA Acting Commissioner Janet Woodcock said in a call to reporters.
To prepare and develop its new guidance, the agency uses its experience with annual flu shots. “Influenza vaccines and diagnostics are regularly adjusted every year to address the predicted predominant strains circulating worldwide. The agency has created and used regulatory processes that facilitate these updates, ”the agency wrote. “We will leverage our experience with influenza to help pave a way forward if SARS-CoV-2 variants emerge against which currently authorized vaccines are not sufficiently effective.”
Moderna, Pfizer and BioNTech have all said they want to adjust their current vaccinations to better protect against emerging variants. Their mRNA-based vaccine design makes it a relatively easy process. The vaccine works by delivering to human cells the genetic blueprint for an important SARS-CoV-2 protein – the peak protein. From there, the cells translate the code into proteins, which then train the immune system to detect and neutralize the virus.
The variants seen so far have critical mutations in their vein proteins, so updating the vaccines is mostly a matter of small changes to the blueprint delivered to cells. BioNTech’s CEO said earlier that the company could make such adjustments in just six weeks.
Similarly, GlaxoSmithKline announced this week that it has partnered with German biotechnology firm CureVac to launch its mRNA-based vaccine – and begin work on the next generation of the vaccine to protect against variants. GSK and CureVac said they are working on developing a “multivalent” mRNA-based vaccine that could potentially protect against multiple variants simultaneously.