Expect an updated Covid-19 vaccine this fall

Cliff notes from FDA's vaccine meeting for fall 2024

Today, the FDA held a much anticipated meeting. Their external scientific committee, VRBPAC, unanimously voted to update the Covid-19 vaccine formula for this fall. Which exact variant will be in the vaccine? We don’t know yet. Will Novavax be an option? That’s a million-dollar question.

Here are your Cliff notes.

Why update the COVID-19 vaccines?

We could keep the same vaccine formula this fall, but several reasons we should update were presented:

1. SARS-CoV-2 continues to mutate—about two times faster than the flu. It’s normal to update vaccines when the virus mutates quickly. For example, we update vaccines for flu (which changes ~annually), but we don’t update vaccines for measles (which hasn’t mutated in a meaningful way for decades).

2. The current circulating variants are meaningfully different from last year’s vaccine. The map below shows the differences—the farther apart, the more different. These are pretty distant, which suggests an updated vaccine would help our immune systems recognize the change.

This is an antigenic cartography figure. It maps how far apart variants are to see how well antibodies are triggered for protection. Figure from FDA; Annotated by YLE

3. Covid-19 vaccines continue to provide additional protection every year but wane at 4 months due to the emergence of new variants. Protection against hospitalization declines (42% effectiveness → 16%) as does protection against ICU admission, albeit to a lesser degree (59% → 32%).

Slide from CDC presentation; Annotated by YLE

It’s really important to recognize that these numbers are relative. Even though vaccine effectiveness is waning, the hospitals aren’t filling up. This is because vaccine effectiveness now represents the incremental benefit above and beyond the baseline protection in the general population. This differs from when we first introduced vaccines and the general population had a very low immunity wall.

What variant should be in the vaccine formula?

Creating, testing, manufacturing, and distributing vaccines takes time, so we must decide as soon as possible. This is especially true for Novavax, a protein vaccine that requires more time to develop than mRNA vaccines.

A few months ago, FDA and World Health Organization anticipated the updated vaccine formula would target JN.1, the dominant variant spreading at the time. So, pharma companies started creating and testing a JN.1 vaccine.

However, other variants (KP.2/KP.3, known as FLiRT) have taken over recently. KP variants only have 2 spike changes compared to JN.1, which isn’t a lot of change, but it may be a sign of the pathway the virus will change going forward.

Slide from FDA presentations, Annotated by YLE

While any vaccine will help against severe disease, variant selection—JN.1 vs. KP— requires other tradeoffs:

• JN.1 option—all vaccines (including Novavax) would be available this fall because they’ve already been working towards this. It also follows what other countries will do. However, this will not be not as effective against infections because the virus has already changed and will continue to change.

• KP.2/KP.3 option—this would be the most up-to-date formula, which will prevent more infections. However, Novavax would not be an option—they can’t change course this late in the year. This may mean fewer vaccinated, as many (including me) prefer Novavax because it has fewer side effects.

FDA didn’t come to a decision today. It seems they are leaning towards JN.1, which I think is the right call.

Yes, the updated vaccine is effective and safe.

Pharma companies presented data on the safety and effectiveness of updated vaccines. They vaccinated monkeys and mice several times and then tested the new formula (this way, it mirrors humans’ immune history).

To no one’s surprise, updated vaccine formulas improved both

• Our first line of defense: Increased neutralizing antibodies, which will help prevent infection.

• Our second line of defense: Novavax tested T-cells—our long-term immunity—and they increased, which will help against severe disease.

And, yes, this is based on animal data.

Because of the minimal change, we are confident that this monkey and mouse data and previous human data will accurately predict safety and effectiveness. An updated formula is literally the difference of a few amino acids—like a few letter edits to a Word document. We aren’t changing the number of words in the paper (like dosage of RNA), the content of the paper, or the platform (like Word to Excel).

Vote

All present VRBPAC members (16) voted in favor of updating the vaccine formula in the fall.

So, what’s next?

The FDA will soon decide on the exact variant. Pfizer, Moderna, and (maybe) Novavax will then start manufacturing millions of vaccines. Once they’re ready, the FDA will approve the updated vaccine. CDC’s external committee—ACIP—will determine who should get the vaccine at the end of the month.

Bottom line

Expect an updated Covid-19 vaccine formula this fall. Who will be eligible and what will be available is still up in the air. We should know more soon.

Love, YLE

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“Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, data scientist, wife, and mom of two little girls. During the day, she is a senior scientific consultant to a number of organizations, including the CDC. At night, she writes this newsletter. Her main goal is to “translate” the ever-evolving public health science so that people will be well-equipped to make evidence-based decisions. This newsletter is free, thanks to the generous support of fellow YLE community members. To support this effort, subscribe below: