Influx of Patients Seeking COVID-19 Boosters and Flu Shots on the Horizon

Clinicians are bracing for the 2022-2023 influenza season and potential surges in COVID-19 infections this fall and winter. After a remarkably subdued 2020 to 2021 flu season, the CDC estimates that during the 2021 to 2022 US flu season there were 8 million to 13 million symptomatic illnesses, 82,000 to 170,000 hospitalizations, and 5000 to 14,000 deaths from influenza.¹ Emergency use authorization (EUA) of bivalent COVID-19 boosters for certain populations, along with an increase in seasonal influenza vaccination efforts, will ensure pharmacists have a very busy season ahead.

The landscape of COVID-19 vaccines has become increasingly complex, with a variety of vaccine types and formulations. This article describes mRNA vaccines that are available and a new adjuvanted recombinant subunit vaccine. Because the adenovirus vector vaccine by Johnson & Johnson’s Janssen is no longer recommended for routine use in the United States, it will not be discussed.² However, it remains available and may have limited utility in practice. Immunizers always should consult the most recent recommendations from the CDC on the clinical use of vaccines.

COVID-19 Vaccines and Boosters Available Fall 2022

mRNA Vaccines and Boosters

There are 2 mRNA vaccines for the prevention of COVID-19 currently available in the United States. These are Moderna’s mRNA-1273 (Spikevax) and Pfizer-BioNTech’s BNT162b2 (Comirnaty). Both vaccines have similar components.^3-5

Spikevax and Comirnaty are lipid nanoparticle-encapsulated mRNA vaccines that encode the full-length wild-type SARS-CoV-2 spike glycoprotein stabilized in its prefusion conformation. Once injected into the muscle, muscle cells translate the mRNA into the spike protein antigen, which mounts an immune response that involves neutralizing antibodies, T helper cells, and cytotoxic T cells.^6,7 Both vaccines include polyethylene glycol-2000 lipids that may lead to hypersensitivity reactions.^4,5 Although anaphylaxis has been reported in some patients, it is rare.⁸ Both vaccines share similar adverse event (AE) profiles.^4,5 The most commonly reported AEs in clinical trials of Spikevax or Comirnaty were pain at injection site, fatigue, headache, myalgia, chills, arthralgia, fever, swelling at the injection site, and erythema at the injection site. Incidence of commonly reported local and systemic reactions was lower in individuals 65 years and older and in those receiving Comirnaty than those receiving Spikevax.⁹ This is likely due to a lower antigen content, although the reasons for these differences are not definitively known. In addition, myocarditis and pericarditis have been observed following vaccination with an mRNA vaccine, particularly in adolescent and young adult males.¹⁰ Studies from several countries have shown that risk is greatest with the second dose of the 2-dose primary series.^10,11 In addition, myocarditis and pericarditis are more likely to occur when the interval for the second dose is less than 30 days following the first dose.^10,11 As a result, the CDC recommends a dosing interval of at least 8 weeks for immunocompetent individuals, and especially for male patients aged 12 to 39 years.¹²

Results from individual phase 3 randomized clinical trials (RCTs) indicate Comirnaty and Spikevax offer similar vaccine efficacy against COVID-19 illness and severe disease.^13,14 However, real-world data suggest subtle variations in immune responses induced by the 2 mRNA vaccines. Although both vaccines induce a robust antibody response in individuals fully vaccinated with the primary series, Spikevax has shown slightly higher effectiveness compared with Comirnaty in prevention of infection.^15,16 This is likely due to its higher antigen content, longer interval between doses, differences in lipid nanoparticle composition, and potentially different characteristics of induced antibodies in terms of antibody isotype or subclass and Fc-mediated effector functions.¹⁶ Nevertheless, vaccine effectiveness against hospitalization and death are comparable among Spikevax and Comirnaty.^17,18 In light of emerging variants of concern (VOC), duration of immunity is difficult to estimate. Results from phase 3 trials and real-world studies indicate a gradual decline in vaccine effectiveness through 6 months with waning humoral response and emergence of VOCs such as Beta and Delta; however, protection against severe disease or hospitalization remained high.^19-25 Still, the rapid spread of Omicron raised concerns about decreased vaccine effectiveness, which led to the recommendation for booster vaccination to restore protection against hospitalization.^26-28

Spikevax

Spikevax was approved by the United States Food and Drug Administration (FDA) for use in adults 18 years and older (Table).^4,5,29-38 Spikevax is authorized for emergency use as a primary vaccination series in individuals 6 months and older, and as a booster in those 18 years and older.³⁰

Comirnaty

Comirnaty was approved by the FDA for individuals 12 years and older (Table).^4,5,29-38 It is authorized for emergency use as a primary series for individuals 6 months and older, and as a booster vaccine for those 5 years
and older.³¹

Bivalent Boosters

In June 2022, an FDA advisory committee voted to include a SARS-CoV-2 Omicron component in COVID-19 booster vaccines in the United States beginning in fall 2022.³⁹ On August 31, 2022, the FDA granted an EUA of the bivalent booster vaccines by Moderna (in adults ≥18 years) and Pfizer (in individuals ≥12 years) that include mRNA components of the original strain and the Omicron variant of SARS-CoV-2.⁴⁰

Adjuvanted Recombinant Subunit Vaccine: Novavax COVID-19 Vaccine

There is 1 adjuvanted recombinant protein subunit vaccine available in the United States and it is the latest addition to the COVID-19 vaccine armamentarium (Table4,5,29-38).41 Similar to mRNA vaccines, the Novavax COVID-19 vaccine contains a recombinant full-length wild-type (Wuhan-Hu-1) SARS-CoV-2 spike glycoprotein stabilized in its prefusion conformation. However, it is made in recombinant baculo- virus infected moth cells (Spodoptera frugiperda) rather than the muscle cells of vaccine recipients.^7,42-44 The spike proteins are extracted, purified, and formulated with polysorbate 80.⁴⁴ The resulting nanoparticles are further coformulated with Matrix-M1 adjuvant, which has been shown to increase immunogenicity while requiring a smaller dose of the vaccine.^42,44 The most common AEs in clinical trials were injection site pain/tenderness, fatigue/ malaise, muscle pain, headache, joint pain, nausea/ vomiting, injection site redness, injection site swelling, and fever.³⁵ The incidence of these AEs was generally lower in older adults (aged ≥65 years) and higher in adolescents (aged 12-17 years). Although myocarditis has been reported with the Novavax COVID-19 vaccine, its occurrence is rare, occurring in just 2 patients who received Novavax (0.01%) in clinical trials.

Results from phase 3 RCTs demonstrated that the Novavax COVID-19 vaccine has high efficacy in symptomatic COVID-19 and severe disease, comparable with mRNA vaccines.^45,46 Given its later use during the pandemic, its real-world effectiveness, especially against Omicron, and duration of protection are largely unknown.

Novavax’s COVID-19 vaccine is authorized for emergency use as a 2-dose primary series for individuals 12 years and older.^34,35 It is not currently authorized as a booster vaccine. A key advantage of the Novavax COVID-19 vaccine is that it can be stored at refrigerator temperatures (36 °F-46 °F) until the expiration date.³³ At the time of this writing, Novavax is seeking an EUA from the FDA of a booster dose of its adjuvanted COVID-19 vaccine in adults 18 years and older.⁴⁷

What Pharmacists Should Expect This Flu Season

The CDC recommends routine annual influenza vaccination for all individuals (aged ≥6 months) who do not have contraindications, with the Advisory Committee on Immunization Practices advising higher dose or adjuvanted vaccines preferentially for older adults (aged ≥65 years) beginning in the 2022-2023 season.^48,49 In addition to an annual influenza vaccine, many individuals will seek COVID-19 vaccines, and many will meet the criteria for receiving their first or even second COVID-19 booster. As of mid-September 2022, about 68% of the US population is fully vaccinated, approximately 12% is partially vaccinated, and another 20% have yet to receive their first COVID-19 vaccine dose.⁵⁰ Many of these individuals may seek an influenza vaccination and COVID-19 vaccination at the same time. Although coformulated influenza/COVID-19 vaccines are under development as mRNA or recombinant subunit vaccines, they will not be available this influenza season.^51,52 Concomitant administration of current influenza vaccines and COVID-19 vaccines is safe and recommended by the CDC.^53-55 Limited evidence suggests that receiving an influenza vaccination does not significantly increase AEs from COVID-19 vaccines. In 1 study, concomitant use of an adjuvanted influenza vaccine (eg, Fluad) with the Novavax COVID-19 vaccine did not increase reactogenicity, with predominately mild AEs generally lasting 1 to 2 days.⁵⁵

Conclusions

COVID-19 vaccines available in the United States are complex, with differences in vaccine technology (ie, mRNA or recombinant protein) formulation and antigen content, storage recommendations, and recommended age for vaccination. The availability of bivalent mRNA COVID-19 boosters, which provide broader protection, will likely increase vaccine demand in the fall. Although at least 2 manufacturers are evaluating combined influenza and COVID-19 vaccines,^51,52 they will not be available for the upcoming influenza season.

About The Authors

Alireza Fakhriravari, PharmD, BCPS, BCIDP, AAHIVP, is director of advanced pharmacy practice experiences at Loma Linda University School of Pharmacy in California.

Michael D. Hogue, PharmD, FAPhA, FNAP, is dean of the School of Pharmacy and professor of pharmacy practice and preventive medicine at Loma Linda University in California.

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