Bivalent Boosters for Covid. What Should You Do?

On August 31, 2022, the Food and Drug Administration (FDA) authorized bivalent COVID-19 vaccines produced by Moderna and Pfizer for emergency use as a booster dose in individuals previously vaccinated. 

• What is the emergency?  According to the CDC’s COVID Data Tracker, cases, deaths and hospitalizations are trending down

In the FDA’s press release, they amended the emergency use authorization of the original Moderna and Pfizer mRNA vaccines to now include the new booster formulations due to waning effectiveness of the original vaccines against the omicron variant.

The original boosters are no longer authorized for use.

The FDA’s decision to authorize the boosters makes this the first vaccine to be authorized without any data from human trials.

The FDA states its decision to authorize the boosters was based on the “totality of evidence.”

This article will review the “totality of evidence” currently available leading to this decision.

What do we Know about the New Bivalent Boosters?

The bivalent boosters, also known as “updated boosters,” contain two components: half of the original mRNA vaccine formulation and half of the mRNA of the omicron variant to better protect against the current dominant omicron subvariants (BA.4/BA.5).  In other words, it contains the genetic material of the original spike protein and genetic material of the spike protein of the omicron variant.

According to the Centers for Disease Control and Prevention, as of September 1st, the omicron subvariants BA.4/5 account for 91.4% of COVID cases in the United States. There are no statistics as to the number of people who have become ill with these subvariants to ascertain heard immunity.

The bivalent boosters were approved to offer further protection against omicron. With omicron subvariant cases accounting for the majority of infections, the FDA voted in favor of the boosters.

“Totality of Evidence” Summary

The FDA’s “totality of evidence” for their approval August 31, 2022, includes the results of:

• A Pfizer animal study of 8 mice,  (Moderna’s 10 mice study was released 9-1-2022)
• clinical data from the original vaccines,
• nonclinical data of a bivalent vaccine not identical to the current variant,
• and a clinical study of a bivalent vaccine “similar to each of the vaccines being authorized” but also not identical.

Both Moderna and Pfizer are due to begin human clinical trials in the near future although the FDA authorized its use before any human or animal clinical trials.  We do not know how effective this vaccine is. Effectiveness has not been studied.

“Totality of Evidence” Preliminary Data from Mouse Studies on 18 Mice

Both Pfizer and Moderna have submitted animal data to the FDA which they have not released to the public. Preliminary data was presented by Pfizer in a June FDA meeting, describing results from their study consisting of eight mice who received the bivalent booster and had their blood drawn to assess for neutralizing antibodies. Neutralizing antibodies cannot be used to determine real-world effectiveness.

Pfizer reports the mice produced a 2.6-fold increase in antibody titers against the omicron BA.5 variant compared to the original mRNA vaccine. Antibody titers against the omicron variant resulted in a wide range, some titers being extremely high, some titers being extremely low, as well as other titers in between the extremes. This was not seen with the original vaccine antibody titers. This suggests inconsistent immune responses in the mice which is not desirable in a product.

We do not know if any mice died, if the mouse with the highest titers was the sickest, if the mouse with the highest titers experienced more severe side effects, if the mouse with the lowest titers did not receive any protection, or how this translates to humans.  If a result is that unpredictable, is it acceptable as a vaccine?  What percent of the mice were protected?  Were the mice exposed to the omicron variant and did they get sick or not?

Moderna’s Preliminary data was presented to the Advisory Committee on Immunization Practices of the CDC on September 1st, 2022.   Ten mice were challenged with the BA.5 strain four weeks after receiving the bivalent booster and then tested for viral counts in their lungs and noses. All ten mice developed COVID, demonstrated by the presence of viral particles in their noses and lungs, however, the BA.5 boosted mice had fewer viral particles in their lungs compared to mice having the original vaccine series and booster.  Also noted were wide ranges of antibodies suggesting inconsistent immune response.

What do we know about the Effectiveness of the Boosters?

Data on vaccine effectiveness of the updated boosters is based on:

• the effectiveness of the primary mRNA vaccines,
• the primary booster with original spike protein
• and a bivalent vaccine not identical to the current bivalent vaccine recently approved by the FDA.…

In other words, effectiveness of the updated boosters at this point is a prediction.   It is not based on scientific data of the new vaccines.  Fact Sheets of the new boosters from both Pfizer and Moderna state, “Bivalent may not protect all vaccine recipients.”

There is no efficacy data for the updated boosters at this time.  The FDA predicts they will provide greater protection.

What do we know about the Safety of the Boosters?

Safety data for the approval of the new boosters is based on the safety data of the original vaccines. The FDA states the safety should be similar to that of the original vaccines because they were created using the same process. There is no safety data specific to the Bivalent Booster.

The following safety data is posted in the Fact Sheets for Healthcare Providers Administering the Vaccine for both Pfizer and Moderna boosters:

• Pfizer:  Postmarketing safety data with Moderna COVID-19 Vaccine are relevant to Moderna COVID-19 Vaccine, Bivalent because these vaccinations are manufactured using the same process.
• Moderna:  Postmarketing safety data with Pfizer-BioNTech COVID-19 Vaccine are relevant to Moderna COVID-19 Vaccine, Bivalent because these vaccinations are manufactured using the same process.

Questions we do not have answers to:

• How will the boosters perform in humans?
• Are the updated boosters safe?
• Are the updated boosters effective?
• What are the long-term safety effects of the original vaccines?
• What are the long-term safety effects of the updated boosters?
• How long will protection last if it is effective?
• How long will omicron be the dominant strain?
• Will there be a new variant, making these boosters obsolete?
• Why is the FDA approving the boosters under emergency authorization?
• What is the emergency?  According to the CDC’s COVID Data Tracker, cases, deaths and hospitalizations are trending down

Current data for the updated boosters is minimal. Important questions remain regarding the safety and real-world efficacy. Human trials have not yet begun to assess the boosters.

As with any treatment, obtaining transparent information is critical when considering the benefits and risks. Current data shows the risk of hospitalization, ICU admittance and death with variants BA.4/5 is low. Currently, no one knows the benefit of this booster.

Have an awesome day!  Dr D