By Dr. Kim Lockheimer, PhD, DFM – Functional Medicine, Integrative Oncology & Precision Health

Seasonal influenza continues to place a major strain on public health. Even with yearly vaccination campaigns, the flu causes millions of illnesses and thousands of hospitalizations in adults each year. One of the biggest challenges? The flu virus changes quickly, and traditional vaccines don’t always match circulating strains—leading to widely variable protection from season to season.

A new nucleoside-modified mRNA (modRNA) influenza vaccine, similar in technology to the mRNA platform used for COVID-19 vaccines, is now being studied as a faster, more adaptable way to protect people from the flu. A recent Phase 3 clinical trial published in The New England Journal of Medicine (NEJM) offers encouraging results.

Below, I break down the study findings in clear language so you can understand what this next generation of flu vaccines may mean for your health.

 

Why Consider an mRNA Flu Vaccine?

 

Traditional flu vaccines are made using chicken eggs or cell culture—a process that takes months and can introduce small mutations that reduce vaccine effectiveness. mRNA vaccines work differently:

  • They contain a blueprint (mRNA) that teaches your immune system to recognize proteins from the flu virus.

  • Production is much faster, allowing better matching to circulating strains.

  • There is no risk of egg-adapted mutations, which can impact effectiveness.

  • mRNA can be rapidly adapted as strains shift.

 

Given the promising results of mRNA technology during COVID-19, researchers are exploring whether this approach can improve seasonal flu protection as well.

 

How the Study Was Designed

 

This Phase 3 trial enrolled 18,476 healthy adults ages 18–64 across the U.S., South Africa, and the Philippines during the 2022–2023 flu season.

Participants were randomly assigned to receive:

  • A quadrivalent modRNA flu vaccine, or

  • A standard quadrivalent inactivated flu vaccine (the current licensed option)

 

The study looked at:

✔️ Vaccine effectiveness

 

How well the mRNA vaccine prevented laboratory-confirmed flu cases.

✔️ Immune response

 

Measured through antibody levels and T-cell activation.

✔️ Safety

 

Reactions in the first week post-vaccination, overall side effects within 1 month, and serious long-term events up to 6 months.

 

Key Findings: How Well Did the mRNA Flu Vaccine Work?

 

1. Better overall protection against the flu

 

The mRNA vaccine reduced flu illness by 34.5% compared to the traditional flu shot.

This means it met the criteria for:

  • Noninferiority (at least as good as the regular vaccine)

  • Superiority (statistically better)

 

This improvement occurred during a season dominated by A/H3N2 and A/H1N1—strains that often cause more severe illness in adults.

2. Stronger immune response to Influenza A strains

 

The mRNA vaccine produced higher antibody levels against A strains (H3N2 and H1N1), which aligns with higher real-world protection.

For B strains, the antibody response did not outperform the standard vaccine, but influenza B circulation was extremely low that season—making it difficult to meaningfully assess real-world protection.

3. More robust T-cell activation

 

Participants receiving the mRNA vaccine showed higher levels of both CD4+ and CD8+ T-cell activity, especially early after vaccination.

This suggests stronger “cellular immunity,” which may offer longer-lasting and broader protection.

 

Safety Profile: What Side Effects Should People Expect?

 

Both vaccines were overall safe, but reactogenicity—short-term immune-related symptoms—was more common with the mRNA vaccine.

Local reactions (sore arm, redness)

 

  • mRNA vaccine: 70%

  • Standard vaccine: 43%

 

Systemic symptoms (fatigue, headache, chills)

 

  • mRNA: 65.8%

  • Standard: 48.7%

 

Fever

 

  • mRNA: 5.6%

  • Standard: 1.7%

 

Most symptoms were mild to moderate and resolved quickly.

Importantly:

 

  • Serious adverse events were rare and similar between groups.

  • No cases of myocarditis or pericarditis were confirmed.

  • No deaths were attributed to vaccination.

 

One participant experienced a significant allergic reaction (a non-classic anaphylactic event), which resolved.

 

What This Means for the Future of Flu Vaccination

 

This study provides strong evidence that:

✔️ mRNA flu vaccines

work at least as well as—and often better than—traditional flu shots

, particularly for the most severe A strains.

 

✔️ Immune responses—both antibodies and T-cells—were stronger with the mRNA vaccine.

 

✔️ Safety is consistent with what we expect from mRNA platforms:

 

More short-term post-vaccine symptoms, but no new serious risks identified.

✔️ Faster, more flexible manufacturing could lead to better strain matching each year.

 

This opens the door for flu vaccination that is:

  • More adaptable

  • More protective

  • Easier to update

  • Potentially more effective across seasons

 

 

My Clinical Takeaway as a Functional Medicine Practitioner

 

This is a significant step forward in influenza prevention. As someone who works at the intersection of immunology, chronic illness, and precision health, I’m encouraged by technologies that increase both immune protection and vaccine adaptability.

While traditional flu vaccines remain important, this next generation of mRNA-based flu vaccines could:

  • Improve protection during severe flu seasons

  • Reduce hospitalizations

  • Offer broader immunity

  • Allow faster responses to viral evolution

 

As always, individual health decisions should be personalized. Not every patient experiences the flu the same way, and people with chronic conditions, immune dysregulation, or complex medical histories should always review vaccine choices with a qualified clinician.

 

Final Thoughts

 

We’re entering an era where influenza vaccination can become more accurate, more responsive, and more effective—using technology that proved invaluable during the COVID-19 pandemic. This study suggests that mRNA flu vaccines could soon reshape how we protect ourselves each season.

If you’d like help assessing your personal flu risk, optimizing your immune health, or integrating functional medicine strategies to support your immune system naturally, I’m here to guide you.