A Phase 2 interventional study of Fluzone and Fluad in Influenza, sponsored by Yale University. Recruiting at 1 site in United States. Open to participants aged 21 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-06-12.
Sponsored by Yale University · Phase 2, Interventional, and Prevention
This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose).
There are two vaccines currently approved for use in adults age 65 and greater: a high-dose (HD) influenza vaccine (Fluzone High-Dose) that contains 4 times the hemagglutinin dose found in the standard vaccine, and a standard-dose (SD) vaccine containing the proprietary MF59 adjuvant (Fluad). Both vaccines give significantly highly antibody responses to influenza in older adults. This study will directly compare the HD and SD vaccines in nursing home residents, the population of older adults most vulnerable to influenza outbreaks and morbidity and mortality. It will comprehensively study the innate and adaptive response to vaccination, as well as elucidate transcriptomic and proteomic signatures of vaccine response.
This is a randomized, open label study comparing the two vaccines currently approved for use in adults age ≥ 65 years: the high-dose influenza vaccine and the MF59 adjuvanted standard-dose vaccine, both quadrivalent. The young group will be comprised of individuals 21-30 years of age, and the older cohorts will consist of nursing home residents ≥65 years. Participants will also be evaluated for evidence of influenza-like illness (ILI). ILI is defined to include clinical presentation in older adults: by the presence of either two respiratory symptoms (cough, sore throat, shortness of breath, and nasal stuffiness) or one respiratory and one systemic symptom (headache, malaise, temperature >99° F, report of feverishness and muscle aches, or altered mental status). Diagnoses of influenza will be confirmed using a real-time polymerase chain reaction (PCR) test on a nasopharyngeal (NP) swab specimen done by the hospital Virology Laboratory and facilitated by the participating medical directors.
Although this is neither an efficacy or effectiveness study, participants will be randomized 1:1 to either the high-dose influenza vaccine or the MF59 vaccine within age strata. This will ensure a non-biased allocation of the two vaccines and attempts to balance participant characteristics within age strata.
1,199 studies on the registry are indexed under Frailty; 430 are open to participants now.
This study's planned enrollment of 96 is above the median of 80 across 681 interventional studies indexed under Frailty.
Browse Frailty studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
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Exclusion Criteria:
Participants age 21-30 years will receive the standard dose Fluad
Biological: Fluad
Participants age 21-30 years will receive the high dose Fluzone
Biological: Fluzone
Participants age ≥65 years will receive standard dose Fluad
Biological: Fluad
Participants age ≥65 years will receive high dose Fluzone
Biological: Fluzone
Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer
Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer
Change in production of IL-6 in monocytes to assess innate immune inflammatory response
Measurement of IL-6 production in monocytes via flow cytometry
Time frame: Baseline and at Day 2, 7, and 28 post-vaccine
Change in Hemagglutination inhibition titer (HAI) in response to vaccination
HAI titers levels in blood measured prior to and at day 28 post-vaccine
Time frame: Baseline and Day 28
Change in transcriptomic analyses of gene expression
RNA-seq analysis of RNA derived from peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP)
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Change in proteomic analyses
Analysis of protein expression using Mass Spectrometry in plasma
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in innate immune function from PBMCs and PRP as assessed using flow cytometry
Analyses will include intracellular production of cytokines including IL-10 and TNF-alpha in monocyte populations from PBMCs and expression of platelet activation markers such as CD63 and P-selectin on platelets. The effects of ex vivo Toll-like Receptor stimulation on these parameters will also be assessed.
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in B and T cell function from PBMCs as assessed using flow cytometry
This will include analysis of number and proportion of antibody-secreting cells post-vaccine, and analyses of T cells following ex vivo stimulation of PBMCs with influenza hemagglutinins.
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Plan to share: Yes — Data with Protected Health Information (PHI) removed on participant demographics and health conditions, and primary and secondary outcome data will be uploaded to the NIH ImmPort as required by the NIH Human Immunology Project Consortium. Publicly available data will be released after publication. Registration on ImmPort required by the NIH. Timeframe for data upload will be approximately 6-12 months after each influenza vaccine season during the study.
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