- Large cluster-randomized crossover study involving nearly 430,000 U.S. adults aged 65 years and older was published in the Journal of the American Medical Association (JAMA) Network Open.
- Adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza in any setting or influenza with emergency department visits or hospitalization.
- Findings support existing ACIP preferential recommendation for use of adjuvanted, higher dose or recombinant influenza vaccines in older adults.
SUMMIT, N.J., May 13, 2026 – CSL Seqirus, a business of CSL (ASX: CSL), today announced the publication of first-season results from a large cluster-randomized crossover study involving approximately 430,000 adults aged 65 years and older, evaluating the relative vaccine effectiveness (rVE) of adjuvanted and high-dose inactivated influenza vaccines during the 2023/24 influenza season.1
The results of this comparative study, published in the Journal of the American Medical Association (JAMA) Network Open, showed that adjuvanted and high-dose influenza vaccines did not differ in vaccine effectiveness against polymerase chain reaction (PCR)-confirmed influenza in any clinical setting or PRC-confirmed influenza with emergency department visits or hospitalization.1
The findings support the U.S. Advisory Committee on Immunization Practices’ (ACIP) preferential recommendation, in place since the 2022/23 season, that adults aged 65 years and older receive either an adjuvanted, higher-dose or recombinant influenza vaccine.2 The results are also consistent with the robust existing body of real-world evidence (RWE) showcasing the comparable effectiveness of adjuvanted and high-dose influenza vaccines in older adults.3,4,5
“As one of the largest cluster-randomized real‑world influenza vaccine studies, these findings add important new evidence showing that adjuvanted and high‑dose influenza vaccines provide comparable protection in older adults. This kind of large‑scale, real‑world data is critical for informing vaccination strategies in populations most at risk from severe influenza and its complications,” said Gregg Sylvester, Chief Medical Officer and Head of R&D, CSL Seqirus.
Key Findings
The cluster-randomized crossover study was conducted within a large integrated U.S. healthcare system and evaluated influenza vaccination under routine clinical care conditions. Medical facilities alternated weekly between administering adjuvanted quadrivalent influenza vaccine (aQIV) or high-dose quadrivalent influenza vaccine (HD-QIV). This study design was intended to approximate individual randomization while reflecting real-world practice:
- There were 836 cases of PCR-confirmed influenza (3.9 per 1,000 persons) identified after adjuvanted vaccine and 867 cases (4.0 per 1,000 persons) after high-dose vaccine.
- For the primary outcome of PCR-confirmed influenza, aQIV was found to be non-inferior to HD-QIV, with an adjusted rVE of 1.5% (95% CI, -8.4% to 10.5%; non-inferiority p<0.001).
- For the secondary outcomes:
- Against PCR-confirmed influenza associated with hospitalization or emergency department visits, adjusted rVE for adjuvanted versus high-dose influenza vaccine was 9.1% (95% CI, -4.0% to 20.4%; non-inferiority p<0.001).
- Against hospitalization for all-cause community-acquired pneumonia (CAP), adjusted rVE was 1.0% (95% CI, -11.4% to 12.0%; non-inferiority p<0.001).
- For all outcomes, the confidence interval indicated no significant difference in effectiveness between the two vaccines.
Impact of Seasonal Influenza on Older Adults
While seasons vary in severity and influenza can affect anyone, during most seasons, people 65 years and older experience the greatest burden of influenza and its complications.2
In recent years, for example, it’s estimated that between 70 percent and 85 percent of seasonal influenza-related deaths have occurred in people 65 years and older, and between 50 percent and 70 percent of seasonal influenza-related hospitalizations have occurred among people in this age group.2
This recent study aligns with past RWE studies that show adjuvanted and high-dose influenza vaccines provide improved protection in older adults compared with standard-dose, nonadjuvanted vaccines.3,4,5
Influenza vaccines remain the best form of protection to help reduce the impact of influenza for adults 65 years and older.
“One of the ongoing challenges in influenza prevention is making sure older adults are protected with vaccines designed specifically for them,” said Jonathan Anderson, Vice President of Medical Affairs, CSL Seqirus. “In the 2025/26 influenza season, the CDC estimates that adults aged 65 years and older have accounted for 53% of flu hospitalizations.6 A robust body of real-world evidence, including the results from this study, continue to reinforce the importance of influenza vaccines for older adults as a key tool in protecting public health.”
About FLUAD
FLUAD® is an adjuvanted trivalent influenza vaccine specifically designed for adults aged 65 and older. Recent data support the strategic importance of FLUAD in improving outcomes for older populations. Data for FLUAD QUADRIVALENT are relevant to FLUAD because both vaccines are manufactured using the same process and have overlapping compositions.
About the Study
This study focused on adults aged 65 and older and evaluated the relative effectiveness of aQIV versus HD-QIV in preventing flu and related hospitalizations. The healthcare facilities are randomized in blocks based on volume in the prior season and geography. In the first week of the influenza vaccination season, one block routinely administered HD-QIV and the other block routinely administered aQIV. In each week following, every facility switched to the alternate formulation on a weekly basis. Individuals received either aQIV or HD-QIV depending on the facility and week in which they were vaccinated.
The analysis in the first season included 429,595 adults ages 65 years and older, of which 212,875 received aQIV and 216,720 received HD-QIV. Outcomes were assessed from October 1, 2023, through April 30, 2024. Participants were followed beginning at least 14 days after vaccination until the earliest of influenza diagnosis, loss of healthcare membership, death, or end of study.
The results showed no significant difference in effectiveness between the two vaccines; the rVE of adjuvanted compared with high-dose influenza vaccine was 1.5% (95% CI: -8.4%, 10.5%) against influenza, 9.1% (CI: -4.0%, 20.4%) against influenza with hospitalization or ED visits, and 1.0% (CI: -11.4%, 12.0%) against hospitalizations for CAP.
Study Limitations
This study is being conducted in a large healthcare system in which facilities routinely administer large quantities of influenza vaccines on a daily basis and individually manage their own vaccine logistics. In practice, facilities generally administered vaccines in a “first in, first out” manner and were not strictly required to swap vaccine formulations exactly at the start of each week. Within the context of a large integrated healthcare system in California, the findings may not be fully generalizable to uninsured populations or to healthcare settings outside of this system.
About Seasonal Influenza
Influenza is a common, contagious seasonal respiratory disease that may cause severe illness and life-threatening complications in some people.7 Influenza can lead to clinical symptoms varying from mild to moderate respiratory illness to severe complications, hospitalization and in some cases, death.8 Because transmission of influenza viruses to others may occur one day before symptoms develop and up to five to seven days after becoming sick, the disease can be easily transmitted to others.8 Preliminary estimates from the Centers for Disease Control and Prevention (CDC) report that during the 2025/26 influenza season, there were an estimated 380,000-780,000 influenza-related hospitalizations in the U.S.9 The CDC recommends annual vaccination for individuals aged six months and older, who do not have any contraindications.10 Since it takes about two weeks after vaccination for antibodies to develop in the body that help protect against influenza virus infection, it is recommended that people get vaccinated before influenza begins spreading in their community.10 The CDC recommends that most people get vaccinated by the end of October.10
About CSL Seqirus
CSL Seqirus is part of CSL (ASX:CSL). As one of the largest influenza vaccine providers in the world, CSL Seqirus is a major contributor to the prevention of influenza globally and a transcontinental partner in pandemic preparedness. With state-of-the-art production facilities in the U.S., the U.K. and Australia, CSL Seqirus utilizes egg, cell and adjuvant technologies to offer a broad portfolio of differentiated influenza vaccines in more than 20 countries around the world.
For more information about CSL Seqirus, visit CSL.com.
About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on x.com/CSL.
For more information about CSL, visit www.CSL.com.
Intended Audience
This press release is issued from CSL Seqirus in Summit, New Jersey, USA and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved CSL Seqirus products may vary from country to country. Please consult your local regulatory authority on the approval status of CSL Seqirus products.
Forward-Looking Statements
This press release may contain forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements.
FLUAD® (Influenza Vaccine, Adjuvanted)
IMPORTANT SAFETY INFORMATION
What is FLUAD® (Influenza Vaccine, Adjuvanted)?
FLUAD is a vaccine that helps protect people aged 65 years and older from the flu. Vaccination with FLUAD may not protect all people who receive the vaccine.
Who should not receive FLUAD?
You should not receive FLUAD if you have a history of severe allergic reactions (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or to a previous influenza vaccine.
Before receiving FLUAD, tell your healthcare provider about all medical conditions, including if you:
- have ever had Guillain-Barré syndrome (severe muscle weakness) within six weeks after getting a flu vaccine. The decision to give FLUAD should be made by your healthcare provider, based on careful consideration of the potential benefits and risks
- have problems with your immune system or are taking certain medications that suppress your immune system, as these may reduce your immune response to the vaccine
- have ever fainted when receiving a vaccine
What are the most common side effects of FLUAD?
- Pain and tenderness where vaccine was given
- Muscle ache
- Tiredness
- Headache
These are not all of the possible side effects of FLUAD.
You can ask your healthcare provider for more information and for advice about any side effects that concern you.
What do I do if I have side effects?
Report any severe or unusual side effects to your healthcare provider.
To report SUSPECTED ADVERSE REACTIONS, contact CSL Seqirus at 1-855-358-8966 or VAERS at 1-800-822-7967 and www.vaers.hhs.gov.
Before receiving this vaccine, please see the full US Prescribing Information for
FLUAD. You can ask your healthcare provider or pharmacist for information about FLUAD that is written for healthcare professionals.
MEDIA CONTACT
Melanie Kerin
+44 7345 433260
Melanie.Kerin@Seqirus.com
GL-FLUD-26-0001
1 Hsiao A, Leong T, Fireman B, et al. Adjuvanted vs High-Dose Influenza Vaccines in Older US Adults: A Cluster Randomized Crossover Study. JAMA Network Open. 2026;9(5):e2610120. doi:10.1001/jamanetworkopen.2026.10120
2 U.S. Centers for Disease Control and Prevention (CDC). Flu and People 65 Years and Older. https://www.cdc.gov/flu/highrisk/65over.htm. Accessed May 2026.
3 DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014;371(7):635–45. (In eng). DOI: 10.1056/NEJMoa1315727.
4 Ku JH, Rayens E, Sy LS, et al. Comparative Effectiveness of Licensed Influenza Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the 2022-2023 Influenza Season Among Adults ≥65 Years of Age. Clin Infect Dis 2024;79(5):1283–1292. (In eng). DOI: 10.1093/cid/ciae375.
5 Domnich A, de Waure C. Comparative effectiveness of adjuvanted versus high-dose seasonal influenza vaccines for older adults: a systematic review and meta-analysis. Int J Infect Dis 2022;122:855–863. (In eng). DOI: 10.1016/j.ijid.2022.07.048
6 CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 16, ending April 25, 2026. Retrieved from: https://www.cdc.gov/fluview/surveillance/2026-week-16.html. Accessed May 2026.
7 CDC. Key Facts about Influenza. Retrieved from: https://www.cdc.gov/flu/vaccines/keyfacts.html. Accessed May 2026.
8 CDC. About Influenza. Retrieved from: https://www.cdc.gov/flu/about/index.html. Accessed May 2026.
9 CDC. Preliminary Estimated Flu Disease Burden 2025-2026 Flu Season. Retrieved from: https://www.cdc.gov/flu-burden/php/php/data-vis/2025-2026.html. Accessed May 2026.
10 CDC. Who Needs a Flu Vaccine and When. Retrieved from: https://www.cdc.gov/flu/vaccines/vaccinations.html. Accessed May 2026.