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On August 31, 2022, the U.S. FDA authorized emergency use of two novel bivalent mRNA COVID-19 vaccines for boosting previous immunizations. The CDC endorsed both products after members of its Advisory Committee on Immunization Practices (ACIP) spent a day analyzing the mounting complexities of COVID vaccination. Summarized below are highlights of their discussion to help clinicians navigate some of the dilemmas of the upcoming winter flu season.
The original Pfizer and Moderna monovalent mRNA COVID-19 vaccines are no longer authorized for use as boosters in the U.S. for adolescents (age, ≥12) and adults. Only children (age, ≤11 years) who received a primary vaccination with a monovalent product can receive a dose of the Pfizer monovalent vaccine as a booster. For everyone else, the new bivalent vaccines are the only boosting options.
Both new vaccines consist of equal portions of mRNA directed against the ancestral 2020 strain of the virus and mRNA directed against the newer Omicron BA.4 and BA.5 variants that dominated U.S. infections during the summer of 2022. The Pfizer product may be used by adolescents (age, ≥12) and adults; the Moderna product may be used only by adults (age, ≥18).
Neither bivalent vaccine comes to market supported by clinical data: All studies with clinical endpoints are ongoing. Animal and preclinical human studies both for these agents and for similar bivalent vaccines targeting earlier viral variants have confirmed excellent antibody production against both ancestral virus and variant strains. The durability of these antibody responses is not entirely clear. Canada, Great Britain, and the European Union have approved earlier bivalent boosters that target Omicron variant BA.1. Neither BA.4/BA.5 bivalent booster that now is authorized by the U.S. FDA is in use elsewhere in the world.
Both new bivalent vaccines elicit local reactions similar to those seen with monovalent vaccines, as well as a similar set of self-limited systemic reactions. The specific incidence of post-booster myocarditis remains unknown, although this complication has been less frequent overall after booster vaccine doses than after the primary vaccine series.
Both new vaccines are intended for use at least 2 months after a previous vaccination (whether a primary series or a first or second booster). A longer interval between vaccinations might improve booster immunogenicity. Many experts suggest waiting at least 3 months before boosting after a natural infection. Coadministration with influenza vaccine is encouraged.
Clinicians should be aware that the new bivalent boosters add several additional vials to the already crowded COVID-19 vaccine shelves. Although color-coded caps help clarify the content and strength of some of these products, others require very careful examination of the labels. ACIP committee members deplored the quantities of documented vaccine administration errors that are being created at least in part by confusing packaging and urged manufacturers to do their part to help clinicians use their products safely.
The efficacy of COVID-19 vaccination and boosting against severe disease is inarguable, and clinicians should urge all patients, particularly those older than 65, to stay current with these new bivalent options. Those who are uneasy because of the lack of clinical outcome data for these products can take some comfort in knowing they are not alone: Members of both the CDC and FDA advisory committees also were concerned. Some argued that boosting with the older monovalent vaccine provides such good protection against severe disease that perhaps we should wait for clinical outcomes data before moving forward. The fact is, though, that we do not probe each winter's new flu vaccine for its specific performance characteristics either — what presumably will become a ritual of annual fall COVID-19 boosting inevitably will require us all to make peace with the same clinical uncertainties that annual flu shots bring.
Clinicians will have to make individual decisions with patients about the best timing for these boosters. Patients planning to attend a high-risk event in the early fall might decide to get a booster a few weeks beforehand. Others might prefer to wait till late fall or early winter in anticipation of the cold-weather surge in respiratory infections. In the end, most answers to uncertainties about the timing and performance of the new boosters in all the many age, health, and vaccine-experienced subgroups of recipients awaits both clinical trial and real-world data.