by Katelyn Jetelina, MPH PhD

Fall COVID-19 boosters will be available soon. This is a notable shift in the pandemic response, as we’ve been using the same vaccine formula throughout the pandemic—one created in early 2020 to fight against the original Wuhan variant. The FDA and CDC (and their external scientific advisory committees) met in June and decided that not only do we need a fall booster, but we should try and match it to Omicron as best we can.

Fall is around the corner and, with it, many questions. Here is my attempt to offer some answers until we have more clarity next week.

What are the new boosters?
The fall booster will be a bivalent vaccine, which means its formula covers two variants: the original Wuhan virus and Omicron (BA.5). As of yesterday, Pfizer and Moderna submitted their emergency use applications to the FDA.

Pfizer: This will be a 30 microgram vaccine, which is the same dosage as the original series. Pfizer is first seeking approval for those aged 12 and older. But they did confirm they are working on a booster for ages 6 months to 11 years. CDC confirmed this in their fall planning guide, saying that we should expect a booster for younger kiddos following the adults.

Moderna: This booster will be a 50 microgram vaccine, which is the same dosage as the original booster and half the dosage of the original Moderna series. They are seeking approval for ages 18 years and older.

Why do we need an updated booster?
Omicron changed the game in terms of evading immunity, which caused protection against infection to wane quickly. Vaccine protection against severe disease wanes, but ever so slightly. Mix this with the fact that coronaviruses thrive in winter, and that Omicron continues to mutate, and there is a strong possibility of a winter resurgence.

We hope that an updated booster this fall will provide three things:

Higher protection. The booster will no doubt increase neutralizing antibodies, which is our first line of defense. Neutralizing antibodies naturally wane over time, but they will temporarily help prevent infection and transmission in the first “X” months of vaccination.

Longer protection. We don’t know “X,” but an updated booster may protect against infection longer than we are currently seeing. Moderna already tested a bivalent vaccine with a Beta formula. (We thought we would need this booster, but then Omicron came on scene.) This data showed neutralizing antibodies waned more slowly than the original vaccine formula and lasted at least 6 months. This is because a booster helps our second line of defense, too: B cells. B cells are antibody factories that, just like factories, can modify their product on the line. These factories will eventually make a product that targets the circulating virus.

(Moderna)
It’s important to note, though, that if we want immunity against infection beyond 6 months, we need new vaccine altogether, like a nasal vaccine.

Broader protection. The third hope is that a booster increases the diversity of our protection. In other words, we hope the updated booster allows our antibodies to “see” more virus parts and “attach” more strongly compared to the antibodies we have right now. We can realistically only broaden or diversify our response by updating the vaccines (or getting infected).

Will the vaccine be effective?
Yes. How much more effective than the current booster is unknown.

We have a lot of human and non-human data showing that an updated vaccine that closely matches circulating variants (like Alpha, Beta, and BA.1) are at least as good as the old vaccines (this is called non-inferiority). But an updated vaccine has strong potential to be better.

No one knows how much better, though, because we don’t have human data. The U.S. originally planned for a BA.1 bivalent booster, so we have a lot of data for this. But Omicron keeps changing remarkably fast. So, the FDA choose to use a BA.5 formula this fall to better “match” the circulating virus. (Notice, this is different approach than what the WHO recommended and what Europe is rolling out—a BA.1 booster.) Because BA.5 is new, we haven’t had time to analyze it in humans; we have to rely on mice data. This is the typical approach for the annual flu vaccine. It’s not perfect, but does work as a good proxy.

So, there is the key tradeoff:

Have an updated booster that matches the circulating variant the best we can, but rely on animal studies OR

Require human data for updated vaccines, but always severely lag whatever variant is circulating.

Pfizer and Moderna are starting the human trials this month. We will, of course, follow the real-world data, too. But demanding an effective vaccine and clinical data is simply a fantasy against this rapidly changing virus. There is absolutely no reason why safety would be any different than with vaccines based on previous variants, either.

What’s next?
The FDA will review the applications submitted from Pfizer and Moderna. ACIP (the external scientific committee for the CDC) will meet next Thursday and Friday (September 1 and 2). This meeting will answer a lot of questions, but some answers I’m anxiously waiting to hear include:

Should older adults wait until October-ish in case the booster does wane more quickly than we think? This may especially make sense if someone was recently infected. There’s clearly a risk/benefit balance here, especially for vulnerable adults.

What animal data do we have? We’ve already seen preliminary mice data from Pfizer. (Spoiler: The BA.5 booster worked great.) I’m very curious to see more, especially from Moderna.

How many people will actually get a booster? Vaccine recommendations do not equal vaccination. ACIP always presents fantastic survey data reflecting public perception. This data will help forecast how this winter may (or may not) look.

What is the plan for unvaccinated people? I have heard rumblings that they will not be able to get an updated booster without getting the original primary series.

After the ACIP meeting, the CDC director will sign off. This means, if all goes well, vaccines should be available the first week of September.

An important note
This will be the last vaccine that is freely to the American public. We could barely find enough money to purchase fall boosters for everyone. Congress has stopped funding the coronavirus response and has invested very little into pandemic preparedness. This will be a tragedy on many fronts.

Bottom line
Fall boosters are coming very soon. We will have a whole lot more clarity next week after the ACIP meeting. I will be in attendance and will report back with Cliff notes.

Love, YLE

In case you missed it:

Original antigentic sin and imprinting: Are boosters a threat?

Why is it so hard to predict the fall?

“Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, biostatistician, wife, and mom of two little girls. During the day she works at a nonpartisan health policy think tank, and 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.