Report 33: Pfizer’s New Two-in-One COVID-19 Booster: Are We the Clinical Trial?

Most important finding: Pfizer’s planned bivalent booster vaccines will not be tested for safety or effectiveness before they are rolled out to the public this fall.

Key detail leading to finding: Pfizer’s fall 2022 booster will be formulated to respond to two extinct or nearly extinct strains of SARS-CoV-2, may be formulated to deliver twice the amount of mRNA than previous Pfizer vaccines, and may be formulated by modifying the mRNA of the previous Pfizer vaccines without safety testing.

Scale of situation: The FDA has directed all COVID-19 vaccine manufacturers to develop bivalent booster vaccines to be ready for fall 2022 without first testing them for safety or effectiveness.

Plain language explanation of key scientific term: Reactogenicity means the side effects that occur soon after vaccination as the body reacts to the vaccine by mounting an inflammatory response.

The Pfizer booster vaccine that people get this fall may have some surprises. The fall 2022 booster will be formulated to respond to two different strains of SARS-CoV-2, one of which is already extinct and the other, an Omicron variant, will surely be in decline by fall. This fall’s Pfizer “bivalent” – i.e., “conferring immunity to two diseases” – booster may be formulated to deliver twice the amount of mRNA than previous Pfizer shots. All with no clinical trials completed. Will the next Pfizer booster have as many (or more) serious side effects as the current vaccine?

On June 30, 2022, the US Food and Drug Agency issued recommendations to vaccine manufacturers for their fall 2022 vaccination campaign. Their recommendation: develop a two-component, or bivalent, COVID-19 booster vaccine that contains mRNA to produce spike protein from both the original virus and from the Omicron strains currently circulating in the United States.

Pfizer seems to have anticipated the FDA’s recommendation, as Pfizer has already begun developing bivalent booster vaccines.

One bivalent booster vaccine that Pfizer is developing will deliver a total dose of 30 micrograms (the same total dose as the original vaccines and boosters): 15 micrograms of the original vaccine and 15 micrograms of Omicron variant vaccine. Will they be safe? Not if the safety findings for Pfizer’s original 30-microgram vaccines, as reported by DailyClout analysts, hold true.

Another bivalent booster vaccine that Pfizer is developing will deliver a total dose of 60 micrograms (twice the total dose as the original vaccines and boosters). This high-dose bivalent booster vaccine will provide 30 micrograms of the original vaccine and 30 micrograms of Omicron variant vaccine—twice the amount that has already resulted in increased risk of serious side effects. 

If Pfizer continues with a 60-microgram bivalent booster vaccine, will it be safe? We know that Walsh et. al (2020) reported on Pfizer’s clinical studies of doses of 10, 20, 30, and 100 micrograms of the original mRNA vaccine. We know that Pfizer chose the 30-microgram dose because the “immune response and toxicity profile at the selected, relatively low, 30-microgram dose level indicate . . . a favorable balance of reactogenicity [side effects] and immunogenicity [viral protection]” (Walsh et al., p.11). And we know that Pfizer suddenly stopped the clinical study of the 100-microgram dose in 12 participants early, noting that “the second dose was not administered because of reactogenicity [side effects] in the participants . . .” (Walsh et al., p. 7). What we don’t know is how many serious side effects will result from a 60-microgram dose of mRNA bivalent booster vaccine.

Nor do we know why the FDA has recommended booster vaccines that target both the original virus and the Omicron strains currently circulating in the United States. By the FDA’s own admission, “there is no evidence to suggest that earlier strains of virus such as the original prototype strain represented in current vaccines . . . are in existence” (FDA, p. 5).

Why would the FDA recommend that bivalent booster vaccines continue to target the original virus strain, which is already extinct?

Additionally, Pfizer has demonstrated to the FDA that Omicron strains circulating in the United States have a history of changing quickly, within a matter of a few months. As shown in Pfizer’s chart (Fig. 1), the currently circulating Omicron strains will probably already be in decline or extinct, like the original strain, when Pfizer introduces its bivalent booster vaccines this fall. 

In making their recommendations for COVID-19 mRNA bivalent booster vaccines, the FDA is proposing to adopt the same approach it uses for updating seasonal influenza vaccines. This approach involves choosing which strains of influenza will dominate the next flu season and then modifying existing influenza vaccines to target those strains. And this approach works (with an effectiveness of 10 to 60%) for influenza in part because influenza is predictable—it strikes in the fall everywhere around the world. But by the FDA’s own admission, “SARS-CoV-2 variants have not appeared in a predictable seasonal pattern and have not always spread globally” (FDA, p. 9).

So will the approach to seasonal influenza vaccines be safe and effective if it is applied to developing bivalent booster vaccines for COVID-19?

Not if Pfizer’s own clinical trials with two versions of its vaccine, with different mRNA sequences, is any indication. Researchers determined that one mRNA version caused too many side effects, noting that “the nucleotide composition of RNA has been reported to affect its immune stimulatory activity and reactogenicity profile . . .” (Walsh et al., p. 11). What unknown or variable physiological side effects can we expect from Pfizer’s modified mRNA bivalent booster vaccines?

Sadly, we won’t know the answers to important questions about this fall’s bivalent booster vaccines until well after they are available to the public. The FDA has asked manufacturers to begin clinical trials with bivalent booster vaccines, but clinical trials take time, and results of these trials will not be available before the FDA’s expected rollout in fall 2022. Instead, the FDA is content “to rely on comparative immunogenicity data due to the time constraints involved in vaccine manufacturing and clinical efficacy evaluation” (FDA, p. 7).

Pfizer’s new bivalent booster vaccines: are they safe and effective?

We will know eventually, but certainly not before the bivalent booster vaccines are in wide use. Are we, the public, going to be Pfizer’s experimental population, yet again?