Optimizing flu protection in older adults: Enhanced vs. standard-dose vaccines
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Influenza is responsible for significant mortality and hospitalization rates in the United States, ranging from 4,900 to 51,000 deaths and 100,000 to 710,000 hospitalizations annually between 2010 and 2023, according to the CDC.
A and B viruses are the predominant influenza types that circulate during influenza seasons, which typically begin in October, peak between December and February, but can last longer than that.
People aged 65 years or older are at a particularly high risk for severe complications from influenza, accounting for 70% to 85% of annual influenza-related deaths and 50% to 70% of influenza-related hospitalizations. Given the substantial disease burden, special consideration is necessary to mitigate morbidity and mortality in this population, namely through annual influenza vaccination.
Recommended vaccines
There are several FDA-approved methods to administer influenza vaccines, including intramuscular injection, nasal spray and jet injector. This year, the U.S. switched to trivalent formulations for all influenza vaccines, removing the influenza B/Yamagata strain, which has not caused a confirmed infection since March 2020 and is believed to have disappeared from circulation.
Since 2022, the CDC has recommended three enhanced influenza vaccines for people aged 65 years or older over standard-dose vaccines that are widely used across all age groups: a high-dose vaccine, a recombinant vaccine and an adjuvanted vaccine.
A clinical trial that included more than 30,000 patients aged 65 years or older demonstrated a 24% reduction in influenza infections among patients who received the high-dose vaccine compared with a standard dose vaccine. Additionally, those who received the high-dose vaccine had significantly higher rates of seropositivity and hemagglutination inhibition titers.
According to Grohskopf and colleagues, there are some observational studies have shown a benefit in taking one of these enhanced vaccines over a standard-dose vaccine, “particularly in prevention of influenza-associated hospitalizations.”
“The size of this relative benefit has varied from season to season and is not observed in all studies in all seasons, making it difficult to generalize the findings to all or most seasons,” they wrote last year in MMWR. “Studies directly comparing [the three enhanced vaccines] with one another are few and do not support a conclusion that any one of these vaccines is consistently superior to the others across seasons.”
If none of the three enhanced vaccines are available, the CDC recommends that older adults receive any other age-appropriate vaccine. The agency advises against using the nasal spray formulation for this age group, recommending the vaccine be given via intramuscular injection to achieve adequate protection.
The optimal time frame for influenza vaccination is September to October, but unvaccinated people should get vaccinated as long as influenza is circulating, according to the CDC. Early vaccination in July or August is discouraged for older adults because of concerns about immunogenicity peaking prematurely and protection potentially waning over the course of the influenza season.
Studies have shown varying durations of immunity conferred by influenza vaccines across different influenza seasons. A study by Petrie and colleagues found that antibody titers to influenza hemagglutinin and neuraminidase decreased slowly over 18 months, with a twofold decrease estimated to take more than 600 days. Conversely, a study by Belongia and colleagues found a significant association between vaccination interval and infection, with the mean interval from vaccination to influenza infection onset being 101.7 days.
Coadministration with other vaccines
The approval of vaccines against COVID-19 and respiratory syncytial virus raised questions about the timing and safety of administering these vaccines alongside an influenza vaccine.
According to the CDC, coadministration of COVID-19, RSV and influenza vaccines is safe, although patients may be more likely to experience mild side effects like fatigue, headache or injection site reactions. However, patients are not required to receive all three vaccines at the same visit, and there is no required minimum wait time between administering the vaccines, allowing flexibility for patients to receive them concurrently or separately throughout the fall and winter seasons, according to the CDC.
Ultimately, the crucial message is to ensure annual influenza vaccinations for people aged 65 years or older, ideally with the high-dose or other enhanced vaccines between September and October. Patients who are willing and able can consider receiving the influenza, COVID-19 and RSV vaccines together or separately, based on their preferences and scheduling convenience.
References:
- Belongia EA, et al. Vaccine. 2015;doi:10.1016/j.vaccine.2014.06.052CDC. Disease burden of flu. https://www.cdc.gov/flu/about/burden/index.html. Last reviewed Feb. 28, 2024. Accessed July 10, 2024.
- CDC. Flu & people 65 years and older. https://www.cdc.gov/flu/highrisk/65over.htm. Last reviewed March 21, 2024. Accessed July 29, 2024.
- CDC. Getting a flu vaccine and other recommended vaccines at the same time. Available at: https://www.cdc.gov/flu/prevent/coadministration.htm. Last reviewed Dec. 8, 2023. Accessed July 12, 2024.
- CDC. Influenza vaccination: A summary for clinicians. https://www.cdc.gov/flu/professionals/vaccination/vax-summary.htm. Last reviewed March 21, 2024. Accessed July 29, 2024.
- CDC. Information for the 2024-2025 flu season. https://www.cdc.gov/flu/season/faq-flu-season-2024-2025.htm. Last reviewed March 14, 2024. Accessed July 29, 2024.
- CDC. Trivalent influenza vaccines. https://www.cdc.gov/flu/prevent/trivalent.htm. Last updated March 14, 2024. Accessed July 29, 2024.
- Grohskopf LA, et al. MMWR Morb Mortal Wkly Rep. 2022;doi:10.15585/mmwr.rr7202a1.
- Kuehn BM. JAMA. 2022; doi:10.1001/jama.2022.12520.
- Petrie JG, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv313.
For more information:
Caitlin Hart, PharmD, is a PGY2 infectious disease pharmacy resident at Denver Health Medical Center.
Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.
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