The story of Moderna's mRNA flu vaccine (mRNA-1010) has recently shifted from a regulatory stalemate to a potential path forward, largely due to a rare public disagreement and subsequent reversal by the FDA.
The Conflict and Reversal
Initially, the FDA had expressed significant hesitation regarding Moderna's data, leading to what reports described as a
However, in a notable turn of events, the FDA
Key Milestones in the Story
The Technology: Unlike traditional flu shots, Moderna uses mRNA technology (the same used in their COVID-19 vaccine), which allows for faster manufacturing and the ability to update the vaccine more quickly to match circulating strains.
Mixed Data: Clinical trials showed the vaccine was highly effective at generating antibodies for the H1N1 and H3N2 strains but struggled to meet the "non-inferiority" bar for the B/Victoria and B/Yamagata strains compared to existing vaccines.
The Resolution: After the public back-and-forth, the
FDA will now consider
Why This Matters
If approved, Moderna's vaccine would be the first mRNA flu shot on the market. This is seen as a crucial step toward their ultimate goal: a combination vaccine that protects against the flu, COVID-19, and potentially RSV in a single annual shot.
Would you like me to look up the latest clinical trial efficacy numbers for Moderna's combination flu/COVID vaccine?
In clinical trials, Moderna's flu vaccine (mRNA-1010) faced a specific regulatory hurdle: while it successfully induced a strong immune response against the "A" strains of the flu, it initially fell short of the required performance standards for the "B" strains.
To understand why this mattered, you have to look at the four specific targets of a "quadrivalent" (four-strain) flu shot:
1. The Targets: A vs. B Strains
Seasonal flu vaccines are designed to protect against four distinct versions of the virus that circulate in humans:
Influenza A (H1N1 and H3N2): These are the "heavy hitters." They are more common, mutate rapidly, and are responsible for most flu-related hospitalizations and all historical pandemics. mRNA-1010 performed exceptionally well here, showing results that were equal to or better than traditional shots.
Influenza B (Victoria and Yamagata): These lineages only infect humans and generally mutate more slowly. While they cause fewer hospitalizations in adults than Type A, they are a major cause of illness in children.
2. The "Non-Inferiority" Bar
In vaccine science, a new product doesn't always have to be "better" than what already exists; it often just needs to prove it is "not unacceptably worse." This is the non-inferiority bar.
The Test: Researchers compare the antibody levels (geometric mean titers) produced by the new vaccine against those produced by an already approved "gold standard" vaccine.
The Result: For the B/Victoria and B/Yamagata strains, Moderna’s early data showed that the antibody levels were lower than those produced by the traditional vaccines. They didn't miss by a lot, but they failed to meet the strict statistical threshold (the "bar") required to prove they were "just as good" as the shots people already get.
3. Why did the mRNA struggle with Type B?
This is a technical challenge scientists are still solving. mRNA vaccines work by teaching your cells to make a specific protein (the hemagglutinin or HA). For reasons not fully understood, the mRNA instructions for the Type B HA proteins didn't seem to "take" as strongly as the instructions for Type A.
Note: Since 2020, the B/Yamagata strain has actually disappeared from global circulation (likely due to COVID-19 lockdowns). As a result, the
have recently recommended moving back to trivalent (three-strain) vaccines that exclude Yamagata entirely. FDA and WHO
Current Status
Moderna has since updated its formulation. Their latest Phase 3 data (from
Would you like me to look up the specific side effects reported in these mRNA flu trials compared to traditional egg-based shots?
