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Clinical Trial
. 2025 Jul;26(7):105625.
doi: 10.1016/j.jamda.2025.105625. Epub 2025 May 30.

Which Enhanced Influenza Vaccine Has the Greatest Immunogenicity in Long-Term Care Residents: The Adjuvanted or the High-Dose Formulation?

Elise M Didion  1 , Joseph D Kass  2 , Dennis J Wilk  3 , Emily Buss  4 , Sarah-Michelle Frischmann  3 , Sabina Rubeck  3 , Richard Banks  4 , Brigid M Wilson  4 , Stefan Gravenstein  5 , David H Canaday  6
Affiliations
Clinical Trial

Which Enhanced Influenza Vaccine Has the Greatest Immunogenicity in Long-Term Care Residents: The Adjuvanted or the High-Dose Formulation?

Elise M Didion et al. J Am Med Dir Assoc. 2025 Jul.

Abstract

Objectives: This study compares enhanced influenza vaccines recommended for older adults, adjuvanted flu vaccine (aTIV, FLUAD) vs high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met noninferiority standards for older long-term care facility (LTCF) residents.

Design: A phase 4, randomized, active-controlled, noninferiority trial on influenza vaccine immunogenicity conducted over 2 influenza seasons (2018-2019 and 2019-2020) (NCT03694808).

Setting and participants: Residents of LTCFs aged ≥65 years.

Methods: Participants were randomized 1:1 to receive either aTIV or HD-IIV3 using computer-generated randomization. Only laboratory personnel were blinded. Hemagglutination inhibition (HAI) and neuraminidase inhibition (NI) assays measured antibody responses at baseline and 28 days postvaccination. The primary outcome compared the geometric mean titers (GMTs) at day 28. Secondary outcomes included seroconversion rates and NI titers.

Results: We randomized 387 LTCF residents to receive either aTIV (n = 194) or HD-IIV3 (n = 193) over 2 flu seasons. We observed noninferior HAI levels at postvaccination day 28 to A/H1N1 and A/H3N2 for aTIV and HD-IIV3 (GMT ratio, 1.03; 95% CI, 0.76-1.4; and GMT ratio, 1.04; 95% CI, 0.73-1.48, respectively), meeting noninferiority criteria with 95% CI upper bounds <1.5. However, noninferiority criteria were not met for influenza B HAI levels (GMT ratio, 1.21; 95% CI, 0.91-1.61). Also, noninferiority criteria for HAI seroconversion were not met for any of the 3 strains. Applying the same noninferiority criteria to NI, both day 28 titer and seroconversion in aTIV were noninferior to HD-IIV3 for A/H1N1 and A/H3N2 strains.

Conclusions and implications: Overall the anti-hemagglutinin and anti-neuraminidase titers demonstrate similarities between the vaccines and support them both being in the enhanced flu vaccine category preferentially recommended by the Centers for Disease Control and Prevention for people aged ≥65 years.

Keywords: Adjuvanted vaccine; aged; high-dose vaccine; immunogenicity; influenza vaccine; long-term care.

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Conflict of interest statement

Disclosure S.G. and D.H.C. are recipients of investigator-initiated grants to their universities from Pfizer to study pneumococcal vaccines, Sanofi Pasteur and Seqirus to study influenza vaccines, Moderna to study respiratory infection, and GSK to study herpes zoster. S.G. is the recipient of an investigator-initiated grant to the university from Genentech on influenza antivirals; reports consulting for GSK, Janssen/Johnson&Johnson, Merck, Novavax, Moderna, Seqirus, and Sanofi; has received honoraria for speaking for AstraZeneca, GSK, Pfizer, Sanofi, and Seqirus; and reports personal fees from Pfizer.

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