For the First Time Ever, CDC Makes Specific Recommendations on Flu Vaccines for Geriatric Patients

Influenza can be a serious illness for all, especially the geriatric population. Those aged 65 years and older face a higher risk of developing grave complications from influenza compared to younger adults. In fact, up to 90% of influenza-related deaths occur in older adults.¹

It is theorized that having the influenza virus causes geriatric patient’s immune system to become overwhelmed, making them more susceptible to other respiratory illnesses like pneumonia.¹ To ensure adequate protection, the CDC recommends that patients annually receive their influenza vaccination starting in September and no later than October. Until the current influenza season, the CDC has never expressed a preference for any of the available influenza vaccines for adults. However, in the CDC’s guidelines for the 2022-23 influenza season, they made explicit recommendations for the geriatric population.

In collaboration with the CDC’s Advisory Committee on Immunization Practices (ACIP), updated guidelines now preference 3 equally recommended immunizations for the influenza virus for older adults: IIV4-HD (Fluzone® High-Dose Quadrivalent; Sanofi Pasteur Inc), RIV4 (Flublok® Quadrivalent Recombinant; Protein Sciences Corporation), and aIIV4 (Fluad® Quadrivalent adjuvanted; Seqirus, Inc) vaccines.² The 3 recommended vaccines have been on the market for several years, and while this is the first influenza season where they are specifically recommended for geriatrics, they have been studied and used in practice in older adults for a number of years.

Standard-dose influenza vaccinations have only been shown to have a 30-50% efficacy in geriatrics.³ This is due to the discovery that the older adults who receive the standard-dose vaccines develop lower influenza-specific antibody titers compared to younger adults. With increasing age, the immune system undergoes a functional change where the signal transduction pathways are less likely to react when exposed to an antigen.
 

Each of the 3 recommended vaccines has shown increased efficacy in older adults compared to conventional influenza immunizations, and all 3 have unique properties to help combat immunogenicity challenges in older adults. It should be noted that most studies comparing the 3 vaccines evaluated their trivalent version. However, it’s not thought that the additional strain of Influenza B in the quadrivalent vaccines would change the outcomes of the comparisons.

What are the differences between the 3 available vaccines?

HD-IIV4 contains 4 times the antigen than the standard-dose.^4-5 Further, a 2014 study in the New England Journal of Medicine showed that the HD-IIV3 had a 24.2% lower incidence of influenza-like illness compared to the standard-dose influenza vaccine in adults aged 65 years and older (HD-IIV3 288/15,990 vs SD-IIV3 301/15,993; [95% CI 9.7 to 36.5; p-value not available]).⁶

IIV4-HD is the least complex vaccine when compared to the other 2 vaccines recommended for older adults, as it is simply a higher dose of the influenza vaccine.⁵ There are no additional ingredients within the vaccine to help with facilitating an increased immune response and antigenic drift. Because of its similarity to standard-dose vaccine HD-IIV4, some clinicians may independently preference the agent solely for the sake of familiarity.

The RIV4 recombinant vaccine (RIV) is made using recombinant technology that is completely egg-free and does not necessitate the need to grow the virus during the manufacturing process.^7-8 This allows it to avoid antigenic influenza adaptations that may occur with egg-based vaccines, offering a potential benefit for increased matching seasonal influenza strains. RIV also contains 45 mcg of hemagglutinin per strain vs 15 mcg hemagglutinin found in IIV4.⁷

In 2017, Dunkle et al. found that RIV was 30% more efficacious than IIV4 in adults over 50 years old (IIV4 138/4,301 vs. RIV4 96/4,303 [95% CI 10 to 47; p = 0.006]).⁸ Additionally, a study by Belongia et al. found that RIV4 created a greater post-vaccination geometric mean titer vs the HD-IIV3 influenza vaccine (RIV4 30/89; 2.0 [95% CI 1.7-2.5; p = 0.04] vs HD-IIV3 29/89; 1.6 [95% CI 1.3-1.8; p-value 0.0001]).⁹

With the challenges of creating an influenza vaccine directly matching the active strains infecting patients, RIV vaccine offers a unique addition of being less likely to succumb to antigenic drift. The CDC also estimates that for the 2022-2023 season, 20% of all influenza vaccinations produced will be egg-free.¹⁰

In previous years, RIV may have been relegated to use in those who were unable or unwilling to take an egg-based vaccine; however, it appears to provide one of the most robust responses in older adults and may prove to be more predictable in annual efficacy than some other influenza vaccines.

The aIIV4 vaccine is made via an egg-based process and it includes an adjuvant called MF95, which is an oil-in-water emulsion made of squalene oil.^11-12 Adjuvants are added to vaccines to act as an immunomodulator and help promote an increased immune response more quickly. A study from Boikos, et al. evaluated both the 2017-2018 and 2018-2019 influenza seasons and compared the trivalent MF95 adjuvanted influenza vaccine (aIIV3) vs the HD-IIV3 or IIV4.13 Overall, aIIV3 was more effective in reducing the number of both inpatient and outpatient influenza-related medical encounters compared to the HD-IIV3 and IIV4 in patients aged 65 years and older.

During the 2017-2018 influenza season, patients who received aIIV3 had 18.2% fewer medical encounters compared to IIV4 (524,223 vs. 917,609; 95%CI 15.8 to 20.5; p-value not reported) and 7.7% fewer encounters compared to HD-IIV3 (aIIV3 524,223 vs HD-IIV3 3,377,860; 95% CI 2.3 to 12.8; p-value not reported). In the 2018-19 season, aIIV3 demonstrated a 27.8% reduction in encounters compared to IIV4 (aIIV3 1,031,145 vs IIV4 915,380;95% CI, 25.7-29.9; p-value not reported) and a 6.9% reduction in encounters compared to HD-IIV3 (aIIV3 1,031,145 vs HD-IIV3 3,809,601; 95% CI, 3.1-10.6; p-value not reported).¹⁰ Based on these results, it appears that an adjuvanted influenza vaccine can provide increased protection for older adults, when compared to IIV4 and HD-IIV3.

All 3 of the vaccinations offer increased efficacy against the influenza virus when compared to the standard-dose influenza vaccine. There is less data comparing all 3 vaccines in current formulations to one-another, though what studies have been conducted suggest that RIV of aIIV4 may produce a better response in older adults.

However, additional studies are needed to confirm these findings. The ACIP recommendations state that all 3 vaccines are equally recommended at the current time.² Table 1 gives information on general vaccine information for each of the 3 options.^5,7,11 Pharmacists can help direct patients on where to receive their influenza vaccine via an online search engine called www.vaccines.gov. Patients should be advised to not postpone getting their vaccination if a particular one is not available in their area. Currently, all 3 vaccines are available and the CDC is not aware of any supply issues.¹⁰

In this particular vulnerable population, the use of one of the 3 CDC recommended influenza vaccinations is imperative to help older adults fight off influenza-virus related morbidity and mortality.

References

1. Iwaskaki A. Why flu is deadly among the elderly. Yale School of Medicine. September 2016. Accessed November 4, 2022. https://medicine.yale.edu/news/medicineatyale/article/why-flu-is-deadly-among-the-elderly/
2. CDC director adopts preference for specific flu vaccines for seniors. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. June 30, 2022. Accessed October 21, 2022. https://www.cdc.gov/media/releases/2022/s0630-seniors-flu.html
3. Cunningham AL, McIntyre P, Subbarao K, et al. Vaccines for older adults. BMJ. February 22, 2021. Accessed October 26, 2022. doi:org.ezproxy3.lhl.uab.edu/10.1136/bmj.n188
4. Fluzone high-dose seasonal influenza vaccine. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. Updated August 25, 2022. Accessed October 21, 2022. https://www.cdc.gov/flu/prevent/qa_fluzone.htm
5. Fluzone® High-Dose Quadrivalent. Sanofi; 2022.
6. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults. New England Journal of Medicine. August 14, 2022. Accessed October 21, 2022. doi:10.1056/NEJMoa1315727
7. Flublok® Quadrivalent Influenza Vaccine. Sanofi; 2022.
8. Dunkle LM, Izikson R, Patriarca P, et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older]. New England Journal of Medicine. June 22 2017. Accessed October 21, 2022. doi:10.1056/NEJMoa1608862
9. Belongia EA, Levine MZ, Olaiya O, et al. Clinical trial to assess immunogenicity of high-dose, adjuvanted, and recombinant influenza vaccines against cell-grown a(h3n2) viruses in adults 65 to 74 years, 2017–2018]. March 30, 2022. Accessed October 21, 2022. doi:10.1016/j.vaccine.2020.02.055
10. Seasonal Influenza Vaccine Supply and Distribution. Centers for Disease Control and Prevention. Updated November 4, 2022. Accessed November 7, 2022. https://www.cdc.gov/flu/prevent/vaccine-supply-distribution.htm
11. Fluad® Quadrivalent. Package insert. Seqirus, Inc; 2022.
12. Durando P, Icardi G, Ansaldi F. MF59-adjuvanted vaccine: a safe and useful tool to enhance and broaden protection against seasonal influenza viruses in subjects at risk. April 10, 2010. Accessed November 2, 2022. https://pubmed.ncbi.nlm.nih.gov/20218923/
13. Boikos C, Fischer L, O’Brien D, et al. Relative Effectiveness of Adjuvanted Trivalent Inactivated Influenza Vaccine Versus Egg-derived Quadrivalent Inactivated Influenza Vaccines and High-dose Trivalent Influenza Vaccine in Preventing Influenza-related Medical Encounters in US Adults ≥ 65 Years During the 2017-2018 and 2018-2019 Influenza Seasons. Infectious Diseases Society of America. September 1, 2021. Accessed November 5, 2022. doi:10.1093/cid/ciab152