By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has amended the emergency use authorizations (EUAs) of the Pfizer-BioNTech and Moderna COVID-19 vaccines. Now, these new bivalent formulations can be used as a single booster dose (after primary or booster vaccination).1 The bivalent vaccines contain the spike protein of the original (i.e., the wild type variant of SARS-CoV-2) and the spike protein in common between omicron subvariants BA.4 and BA.5. The bivalent vaccines are endorsed by the CDC and the Advisory Committee on Immunization Practices.
INDICATIONS
The Moderna COVID-19 vaccine, bivalent can be administered to patients age 18 years and older. The Pfizer-BioNTech COVID-19 vaccine, bivalent can be administered to patients age 12 years and older.1
DOSAGE
Bivalent vaccines are administered as a single booster dose at least two months after either completion of primary vaccine (any authorized monovalent vaccine) or receipt of the most recent approved monovalent booster COVID-19 vaccine. For the Moderna shot, each 0.5 mL contains 50 mcg (25 mcg of the original [wild type]) spike protein and a dose of 25 mcg of omicron BA.4/BA.5 subvariant spike protein. For the Pfizer-BioNTech shot, each 0.3 mL (30 mcg) contains 15 mcg of the original (wild type) spike protein and a dose of 15 mcg of omicron BA.4/BA.5 subvariant spike protein.
POTENTIAL ADVANTAGES
The bivalent COVID-19 vaccine provides protection against the currently circulating omicron subvariant BA.4/BA.5 that is predicted to spread widely this fall and winter.1
POTENTIAL DISADVANTAGES
The bivalent vaccine authorizations were not based on direct human clinical trial data but based on totality of available evidence (e.g., safety, immunogenicity, and reactogenicity).1-3 Adverse reactions are expected to be those commonly reported for the monovalent mRNA COVID-19 vaccines.1,3 The vaccine may not protect all recipients.
COMMENTS
Data submitted to the FDA for authorization were based on extensive safety and effectiveness testing of each monovalent mRNA vaccine and clinical trials from the variant BA.1-adapted vaccine.1-3 Both vaccines showed potent neutralizing antibody response against omicron subvariants BA.4 and BA.5, regardless of prior infection or age. The Moderna bivalent booster was evaluated in a Phase II-III study of the new bivalent vaccine (BA.1) vs. the previously authorized booster. The primary objectives were to assess safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose. Sequential groups of patients received the bivalent vaccine (n = 437) or the original booster (n = 377). The bivalent vaccine elicited neutralizing antibody responses against omicron (including BA.4 and BA.5) that were superior to those of the original booster without evident safety concerns.3
CLINICAL IMPLICATIONS
The mRNA platform allows the updating vaccines to accommodate current and predicted circulating variant and subvariants. The new bivalent vaccine shows a comparable safety profile to the previous booster while eliciting superior levels of neutralizing antibodies to omicron variants. The CDC is recommending all teenagers and adults receive the new booster if it has been at least two months since the primary vaccination or last booster. Older Americans, those with chronic illnesses and immunocompromised, or pregnant individuals should take the new booster as soon as possible.
REFERENCES
1. Pfizer. Pfizer and BioNTech submit application to U.S. FDA for emergency use authorization of omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine. Aug. 22, 2022.
2. Moderna. Moderna completes application to U.S. Food and Drug Administration for emergency use authorization of omicron-targeting bivalent COVID-19 booster vaccine, MRNA-1273.222. Aug. 23, 2022.
3. Chalkias S, Harper C, Vrbicky K, et al. A bivalent omicron-containing booster vaccine against COVID-19. N Engl J Med 2022; Sep 16. doi: 10.1056/NEJMoa2208343. [Online ahead of print].
The FDA has amended the emergency use authorizations of two leading COVID-19 vaccines. Now, these new bivalent formulations can be used as a single booster dose (after primary or booster vaccination).
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