Published Large U.S. Study Finds Comparable Effectiveness Between Adjuvanted and High-Dose Influenza Vaccines in Adults 65 Years and Older

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.^[i]

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 Canada’s National Advisory Committee on Immunization’s (NACI) preferential recommendation, in place since the 2024/25 season, that adults aged 65 years and older receive either an adjuvanted, higher-dose or recombinant influenza vaccine.^[ii] 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.^{[iii],[iv],[v]}

“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 the rate of death attributed to influenza was 108.8 per 100,000 in people 65 years and older, and the rate of respiratory hospitalization attributed to influenza was 144.9 per 100,000 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.^[vi] 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 frequently occurring, 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.⁷ Because transmission of influenza viruses to others may occur before symptoms develop and up to 5 to 7 days after becoming sick, the disease can be easily transmitted to others.⁷ Influenza causes an average of 12,200 hospitalizations and approximately 3,500 deaths each year in Canada.⁸ The National Advisory Committee on Immunization (NACI) recommends that influenza vaccine should be offered annually to anyone 6 months of age and older who does not have a contraindication to the vaccine.⁸ Since it takes about two weeks after vaccination for antibodies to develop in the body and help protect against influenza virus infection, it is recommended that people get vaccinated before influenza begins spreading in their community.⁹ The NACI recommends that people get vaccinated as soon as feasible after the vaccines become available in the fall.⁸

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 Australia, the U.K. and U.S, 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 leading global biopharma 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, dialysis 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 29,000+ 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 CSL.com/Vita.

For more information about CSL, visit 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, Surface antigen, Inactivated, Adjuvanted with MF59C.1)

Indication and clinical use:

FLUAD^® is an inactivated influenza virus vaccine against influenza subtypes A and B contained in the vaccine, indicated in adults 65 years of age and older.

Relevant warnings and precautions:

Do not use FLUAD^® if:

• there is a history of hypersensitivity to egg proteins or other components of the vaccine, any of the excipients or in people who have had a life-threatening reaction to previous influenza vaccination.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take FLUAD^®. Talk about any health conditions or problems you may have, including if you:

• are allergic to eggs or egg-products
• are allergic to any of the following: kanamycin and neomycin sulphate, hydrocortisone, formaldehyde, cetyltrimethylammonium bromide, or polysorbate 80
• have a fever, or you think you may be getting a fever
• had a serious reaction to any flu vaccine in the past
• have any known allergies
• have experienced any health problems
• are currently on any medication (i.e. immunosuppressant, theophylline, anticoagulants such as warfarin)

Other warnings you should know about:

• FLUAD^® should not be administered to anyone with known allergies to eggs or egg products, or any other constituent of the vaccine or to anyone who has had a life-threatening reaction to previous influenza vaccination.
• If Guillain-Barré Syndrome (GBS) has occurred within six weeks of previous influenza vaccination, the decision to give FLUAD^® should be based on careful consideration of the potential benefits and risks.
• Immunocompromised patients may have a diminished immune response to FLUAD^®.
• FLUAD^® may be given at the same time as other vaccines.
• Do not mix with any other vaccine in the same syringe.
• As with any vaccine, immunization with FLUAD^® may not protect 100% of individuals against influenza disease.
• Immunosuppressive therapies may reduce immune response to FLUAD^®.

For more information:

Find the full product monograph that is prepared for healthcare professionals and includes Patient Medication Information by visiting the Health Canada website:https://health-products.canada.ca/dpd-bdpp; the manufacturer’s website http://www.cslseqirus.ca, or by calling 1-855-358-8966.

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MEDIA CONTACT

Melanie Kerin
+44 7345 433260

Melanie.Kerin@Seqirus.com

CAN-CRP-26-0009

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