Systems Investigation of Vaccine Responses in Aging and Frailty
Influenza
What this study involves
The registry says this study is recruiting. Individual locations may have different availability.
- Study type
- Interventional
- Phase
- Phase 2
- Age range
- 21 years - Not specified
- Sex eligible
- All sexes
- Healthy volunteers
- Accepted
- Participants
- 96 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
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).
Read the full description
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.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
- Age 21-40 or 65 and older
- Ability to understand and give informed consent (surrogate consent may apply to nursing home subjects who are decisionally impaired, with verbal assent to be obtained from subject)
- Plan to be in the New Haven, CT area for the next 4-6 weeks
Exclusion Criteria:
- Current use of medication, such as antibiotics in past two weeks. To clarify, patients taking antibiotics for the reason of a current acute infection will not be eligible. Those potential participants receiving antibiotics for prophylaxis purposes will be eligible to participate. The intention is not to create a separate group to drawn conclusions, but not to exclude these participants who are not acutely ill.
- Evidence of acute infection, identified by self- report of fever or symptoms in past two weeks
- Treatment for cancer in past three months.
- Previous adverse reaction to influenza vaccine requiring medical attention, such as allergic response (rash, anaphylaxis) or Guillain-Barré syndrome.
- Pregnant/possibly pregnant.
- History of organ, bone marrow or stem cell transplant, liver cirrhosis, kidney disease requiring dialysis, HIV/AIDS, hepatitis C or active hepatitis B
- Blood donation of 1 pint or more in past 2 months
- Treatment with clinical trial medication
- Presence of any other condition (e.g., geographical or social), actual or projected, that the investigator feels would restrict or limit the patient's participation for the duration of the study. This provision includes participants who have 50% or more missed appointments in the last three months.
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Random assignment
- Masking
- No masking
21-30 standard dose Fluad
Participants age 21-30 years will receive the standard dose Fluad
Biological: Fluad
21-30 high dose Fluzone
Participants age 21-30 years will receive the high dose Fluzone
Biological: Fluzone
≥65 years standard dose Fluad
Participants age ≥65 years will receive standard dose Fluad
Biological: Fluad
≥65 years high dose Fluzone
Participants age ≥65 years will receive high dose Fluzone
Biological: Fluzone
Fluzone BIOLOGICAL
Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer
Fluad BIOLOGICAL
Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Change in production of IL-6 in monocytes to assess innate immune inflammatory response
Time frame: Baseline and at Day 2, 7, and 28 post-vaccine
Measurement of IL-6 production in monocytes via flow cytometry
Secondary measures
Change in Hemagglutination inhibition titer (HAI) in response to vaccination
Time frame: Baseline and Day 28
HAI titers levels in blood measured prior to and at day 28 post-vaccine
Change in transcriptomic analyses of gene expression
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
RNA-seq analysis of RNA derived from peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP)
Change in proteomic analyses
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Analysis of protein expression using Mass Spectrometry in plasma
Number of participants with changes in innate immune function from PBMCs and PRP as assessed using flow cytometry
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
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.
Number of participants with changes in B and T cell function from PBMCs as assessed using flow cytometry
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
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.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.
1 locations
Yale School of MedicineNew Haven, Connecticut, United StatesRecruiting
Study team and timeline
- Lead sponsor
- Yale University
- Study start
- Nov 6, 2023 Actual
- Primary completion
- 2029-05 Estimated
- Study completion
- 2029-05 Estimated
- First posted
- Mar 23, 2022 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
Official study title
Systems Investigation of Vaccine Responses in Aging and Frailty
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 11, 2026 · Last registry update: Nov 10, 2026