What are the latest updates and recommendations on vaccination against COVID-19?

Introduction
Many pharmaceutical companies initiated development and research of SARS-CoV-2 vaccines after the outbreak of COVID-19 in early 2020.¹ Clinical trials evaluating vaccine candidates in humans began in the spring of 2020, and the US Food and Drug Administration (FDA) issued its first emergency use authorizations (EUAs) for the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines in December 2020 based on trial results suggesting approximately 95% efficacy of the vaccines for prevention of COVID-19.² At that time, the Advisory Committee on Immunization Practices (ACIP) recommended the Moderna vaccine in persons aged 18 years or older and the Pfizer-BioNTech vaccine in persons aged 16 years or older to prevent COVID-19. Official FDA approval of the mRNA COVID-19 vaccines was granted in adults in August 2021 for the Pfizer-BioNTech COVID-19 vaccine and in January 2022 for the Moderna COVID-19 vaccine.

Emergency use authorization for the initial Moderna and Pfizer-BioNTech COVID-19 vaccines was expanded to allow for administration to adolescents in the spring of 2021, with authorization further expanded to children 5 to 11 years of age in November 2021 and to everyone ≥6 months of age in the summer of 2022.² During the time that the mRNA vaccines were being developed and authorized, additional vaccines with varying mechanisms of action were also under various stages of development, including viral vector vaccines (developed by Janssen/Johnson & Johnson and AstraZeneca and later discontinued) and protein subunit vaccines (eg, Novavax).

At the time of initial COVID-19 vaccine development, all vaccines were formulated to target the original strain of COVID-19 present in the US.³ However, variant strains of the original virus emerged over time, leading to enhanced transmission and increased infection with COVID-19 despite increasing rates of vaccination. By December 2020, the first COVID-19 variant strain, B.1.1.7 (“Alpha”) was detected in the US.² Since then, numerous other COVID-19 variants have been detected and spread throughout the US, leading to increased viral transmission and reduced vaccine effectiveness. As a result, there have been several changes to the available vaccine formulations and recommendations surrounding their use. Therefore, the purpose of this FAQ is to describe updates to COVID-19 vaccine recommendations over time and review the latest vaccine recommendations.

SARS-CoV-2 variants and associated vaccine changes over time
The SARS-CoV-2 virus mutates continuously and has evolved to different variants over time.³ Spike proteins are located on the surface of the virus; they bind to host cell angiotensin-converting enzyme 2 receptors and trigger fusion with the host cell leading to infection.⁴ Antibodies to the spike protein bind to the protein and inhibit the virus’ ability to bind to the host cell, thus preventing viral propagation and subsequent infection. Therefore, the spike protein is the antigenic target of the COVID-19 vaccines. The SARS-CoV-2 virus has undergone numerous mutations over time, many of which occur in the spike protein. Mutations in the spike protein can lead to a higher affinity for the host cell receptors. As a result, these variants can replicate more easily, escaping from humoral immunity; thus, they have a higher transmission rate. These mutations are also associated with reduced vaccine effectiveness since the mutated spike protein may be less likely to bind to and be neutralized by vaccine-induced antibodies.

The Alpha variant was the first known COVID-19 variant, initially discovered in the United Kingdom.¹ Full vaccination with the initial mRNA COVID-19 vaccines was found to provide sufficient protection against the Alpha variant.⁵ However, in September 2021, a new variant emerged (Delta, B.1.617.2), which was associated with reduced vaccine effectiveness.^6,7 During the time that the Delta variant predominated in the US, effectiveness of the primary series of the mRNA COVID-19 vaccines was found to be 75% to 84% in adults aged 65 years or older and 53% in people at long-term care facilities.⁴ At that time, ACIP recommended COVID-19 vaccine boosters for high-risk populations, including immunocompromised patients and those with certain underlying health conditions at risk for severe infection.^2,8,9

In late 2021, the Omicron variant emerged and replaced the Delta variant to become the dominant strain in the US.² Although the risk of severe infection caused by Omicron is less than other variants, the Centers for Disease Control and Prevention (CDC) and FDA recommended booster vaccines for all eligible patients in November 2021 in anticipation of the Omicron surge.^2,10 By early 2022, the Omicron variant accounted for approximately 99% of COVID-19 cases in the US due to its enhanced transmissibility compared to the Delta variant.² By January 2022, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for administration of booster doses to individuals aged 12 to 15 years.

The Omicron variant continued evolving to subvariants BA.4 and BA.5 with greater infectiousness.² In August 2022, the FDA updated the EUA for the Moderna and Pfizer-BioNTech vaccines to authorize use of new bivalent formulations, which contained mRNA components targeting both the original COVID-19 strain and the BA.4/BA.5 Omicron subvariant strains.¹¹ Until more recently, the bivalent mRNA booster vaccines were the only mRNA vaccines available in the United States. Due to the rising prevalence of Omicron subvariant XBB.1.5 in mid-2023, the FDA suggested that manufacturers update their 2023/2024 vaccines to a monovalent formulation with an XBB.1.5 composition.¹² As of October 2023, the dominant Omicron subvariant is EG.5, followed by HV.1.¹³

Available products
Currently, there are 3 COVID-19 vaccines available in the United Sates which have an XBB.1.5 composition: the Novavax 2023-2024 protein adjuvant vaccine and the updated 2023-2024 Pfizer-BioNTech and Moderna mRNA vaccines.^14-18 Spikevax is the FDA-approved formulation of the Moderna COVID-19 vaccine, and Comirnaty is the FDA-approved formulation of the Pfizer-BioNTech COVID-19 vaccine. Novavax, Spikevax, and Comirnaty are approved for individuals older than 12 years. Pfizer-BioNTech and Moderna also have separate COVID-19 vaccines that are authorized for use in children aged 6 months to 11 years under EUA. Details of the currently available COVID-19 vaccines are provided in Table 1 below.

The original monovalent Pfizer-BioNTech and Moderna COVID-19 vaccines are no longer authorized in the US since April 2023, because they do not provide protection against the currently circulating Omicron strains.¹⁹ The Janssen/Johnson & Johnson COVID-19 vaccine, a viral vector vaccine previously available as a one-dose option, is not available since the remaining stock of the vaccines expired in May 2023; the CDC has requested that any remaining stock be disposed of in accordance with local, state, and federal regulations.²⁰ The bivalent Pfizer-BioNTech or Moderna COVID-19 vaccines are no longer authorized since they do not contain the component to cover the currently widespread Omicron variant, XBB.1.5.²¹

COVID-19 vaccine administration: current recommendations
The current dominant Omicron subvariant in the United States is EG.5.¹³ The subvariant EG.5 has a very similar spike protein makeup to XBB.1.5, and it is a descendant of XBB.1.9.2.²² Although updated COVID-19 vaccines do not contain components specifically corresponding to EG.5, they can provide an effective immune response to EG.5.^22,23

In September 2023, the CDC published interim recommendations for COVID-19 vaccination, taking the new vaccine formulation into consideration.²⁴ In general, any unvaccinated individual should be fully vaccinated with an updated COVID-19 vaccine. Individuals aged 12 years and older should receive 1 dose of the updated COVID-19 vaccine if they have not received the updated COVID-19 vaccine in the past.^21,22 Additional doses may be required for patients aged between 6 months to 11 years or with an immunocompromised status. Children aged 6 months to 4 years who previously received monovalent or bivalent vaccines should complete the vaccination series with an updated mRNA vaccine from the same manufacturer that they received for their original vaccinations, and people ages 5 years and older who previously received monovalent or bivalent vaccines can receive the updated mRNA vaccine from either Moderna or Pfizer-BioNTech. If there are no contraindications, COVID-19 vaccines may be administered simultaneously with other routine vaccines for children, adolescents, and adults. Currently, there are no COVID-19 vaccines available for individuals below 6 months of age. Specific recommendations for COVID-19 vaccination among patients aged 6 months to 4 years and those ≥5 years of age are summarized in Tables 2 and 3 below.

Pediatric patients between 6 months to 4 years old should complete a full vaccine series with vaccines from the same manufacturer.²⁵ Immunocompromised patients of all ages should also be fully vaccinated with vaccines from the same manufacturer, except for those who are 12 years or older and decide to be vaccinated with the Novavax COVID-19 vaccine. Consider extended (8-week) intervals between the first and second doses for patients not moderately or severely immunocompromised to decrease the risk of myocarditis and pericarditis. Extended interval dosing is not indicated for immunocompromised patients due to the higher risk of COVID-19 infection and complications.

Conclusion
The COVID-19 vaccines are proven to reduce the risk of hospitalization and death from COVID-19. The FDA and CDC have continuously updated the recommendations regarding administration of the COVID-19 vaccines due to rapid mutations in the SARS-CoV-2 virus necessitating administration and formulation changes. Currently, Omicron is still the dominant strain of SARS-CoV-2, and EG.5 is the most common Omicron subvariant in the United States. For the 2023-2024 season, the FDA requested that COVID-19 vaccine manufacturers to update their vaccines to a monovalent XBB.1.5 composition to be effective against sublineages XBB.1.5 and EG.5. Currently, interim recommendations for administration of these vaccines are provided by the CDC. Providers should regularly consult relevant product information and the CDC website for the most up to date recommendations regarding COVID-19 vaccination.

References

1. The development of COVID-19 vaccines in the United States: why and how so fast?. Vaccine. 2021;39(18):2491-2495. doi:10.1016/j.vaccine.2021.03.077
2. CDC museum COVID-19 timeline. Centers for Disease Control and Prevention. Updated March 15, 2023. Accessed October 3, 2023. https://www.cdc.gov/museum/timeline/covid19.html
3. Hogan AB, Doohan P, Wu SL, et al. Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach. Nat Commun. 2023;14(1):4325. doi:10.1038/s41467-023-39736-3
4. Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586(7830):516-527. doi:10.1038/s41586-020-2798-3
5. Zeng B, Gao L, Zhou Q, Yu K, Sun F. Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis. BMC Med. 2022;20(1):200. doi:10.1186/s12916-022-02397-y
6. ACIP evidence to recommendations for use of COVID-19 vaccine booster doses. Centers for Disease and Control and Prevention. Updated October 29, 2021. Accessed October 24, 2023. https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-booster-doses-etr.html
7. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N Engl J Med. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891
8. CDC Statement on ACIP booster recommendations. Centers for Disease Control and Prevention. Updated September 24, 2021. Accessed October 24, 2023. https://www.cdc.gov/media/releases/2021/p0924-booster-recommendations-.html
9. Mbaeyi S, Oliver SE, Collins JP, et al. The Advisory Committee on Immunization Practices’ interim recommendations for additional primary and booster doses of COVID-19 vaccines – United States, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(44):1545-1552. doi:10.15585/mmwr.mm7044e2
10. Arabi M, Al-Najjar Y, Mhaimeed N, et al. Severity of the Omicron SARS-CoV-2 variant compared with the previous lineages: A systematic review. J Cell Mol Med. 2023;27(11):1443-1464. doi:10.1111/jcmm.17747
11. Coronavirus (COVID-19) update: FDA authorizes changes to simplify use of bivalent mRNA COVID-19 vaccines. U.S. Food and Drug Administration. Updated April 18, 2023. Accessed October 4, 2023. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-changes-simplify-use-bivalent-mrna-covid-19-vaccines
12. Updated COVID-19 vaccines for use in the United States beginning in fall 2023. U.S. Food and Drug Administration. Updated June 16, 2023. Accessed October 4, 2023. https://www.fda.gov/vaccines-blood-biologics/updated-covid-19-vaccines-use-united-states-beginning-fall-2023
13. COVID data tracker. Centers for Disease Control and Prevention. Updated October 4, 2023. Accessed October 4, 2023. https://covid.cdc.gov/covid-data-tracker/#variant-proportions
14. Spikevax. Prescribing information. Moderna, Inc; 2023. Accessed October 4, 2023. https://www.fda.gov/media/155675/download?attachment
15. Moderna COVID-19 vaccine. Fact sheet. Moderna, Inc; 2023. Accessed October 5, 2023. https://www.fda.gov/media/167208/download?attachment
16. Comirnaty. Prescribing information. Pfizer, Inc; 2023. Accessed October 5, 2023. https://www.fda.gov/media/151707/download?attachment
17. Pfizer-BioNTech COVID-19 vaccine. Fact sheet. Pfizer, Inc; 2023. Accessed October 5, 2023. https://www.fda.gov/media/167211/download?attachment
18. Novavax COVID-19 vaccine, adjuvanted. Fact sheet. Novavax, Inc; 2023. Accessed October 3, 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5b237fbc-d58a-4ca0-a56b-f9425d14dab5&type=display
19. Coronavirus (COVID-19) update: FDA authorizes changes to simplify use of bivalent mRNA COVID-19 vaccines. U.S. Food and Drug Administration. Updated April 18, 2023. Accessed October 16, 2023. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-changes-simplify-use-bivalent-mrna-covid-19-vaccines
20. Janssen (Johnson & Johnson) COVID-19 vaccine. Centers for Disease Control and Prevention. Updated May 10, 2023. Accessed October 16, 2023. https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/index.html
21. FDA takes action on updated mRNA COVID-19 vaccines to better protect against currently circulating variants. U.S. Food and Drug Administration. Updated September 11, 2023. Accessed October 5, 2023. https://www.fda.gov/news-events/press-announcements/fda-takes-action-updated-mrna-covid-19-vaccines-better-protect-against-currently-circulating
22. Will this fall’s updated COVID-19 vaccines be effective against EG.5? Infectious Diseases Society of America. Updated August 16, 2023. Accessed October 5, 2023. https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/will-new-covid-vaccines-work-against-eg.5#/+/0/publishedDate_na_dt/desc/
23. Updated COVID-19 vaccine recommendations are now available. Centers for Disease Control and Prevention. Updated September 12, 2023. Accessed October 5, 2023. https://www.cdc.gov/respiratory-viruses/whats-new/covid-vaccine-recommendations-9-12-2023.html#:~:text=People%20 vaccinated%20with%20Moderna’s%20 updated,FL.1.5.1
24. Use of COVID-19 vaccines in the United States: interim clinical considerations. Centers for Disease Control and Prevention. Updated September 15, 2023. Accessed October 5, 2023. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html
25. Updated (2023–2024 Formula) COVID-19 Vaccine. Centers for Disease Control and Prevention. Updated September 22, 2023. Accessed October 6, 2023. https://www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdf

Prepared by:
Chia Chieh Liang
PharmD Candidate Class of 2024

Edited by:
Jessica Elste, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

November 2023

The information presented is current as of October 6, 2023. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.