Evaluating the Immune Response to Intradermal Seasonal Influenza Vaccine in Healthy Individuals and Cancer Patients
This early phase I trial evaluates the effect of intradermal (ID) seasonal influenza vaccination with Fluzone, registered trademark, on the immune system response and to identify how healthy individuals and cancer patients differ in their response. Fluzone, a seasonal influenza vaccination, works by triggering the immune system to build a defense to the influenza virus. Currently, Fluzone is only approved to be given intramuscularly (IM). The skin acts as both a physical barrier and an immunologic barrier and studies have shown that giving influenza vaccines ID have shown similar results to IM administration. Studying samples of skin in the laboratory from patients receiving a Fluzone vaccination ID may help doctors learn more about the effects of Fluzone on the immune system response in healthy individuals and cancer patients.
Inclusion Criteria
- HEALTHY PARTICIPANTS: Provision of signed and dated informed consent form
- HEALTHY PARTICIPANTS: Stated willingness to comply with all study procedures and availability for the duration of the study, as well as have de-identified samples and data stored for future research
- HEALTHY PARTICIPANTS: Able to proficiently speak, read, and write English
- HEALTHY PARTICIPANTS: Male or female, aged 18-40 years old at time of initial enrollment * Participant is allowed to participate in subsequent influenza seasons even if they will be > 40 years old
- HEALTHY PARTICIPANTS: In good general health as evidenced by medical history
- NON-HEALTHY (CANCER) PARTICIPANTS: Provision of signed and dated informed consent form
- NON-HEALTHY (CANCER) PARTICIPANTS: Stated willingness to comply with all study procedures and availability for the duration of the study, as well as have de-identified samples and data stored for future research
- NON-HEALTHY (CANCER) PARTICIPANTS: Able to proficiently speak, read, and write English
- NON-HEALTHY (CANCER) PARTICIPANTS: Deemed eligible to receive an influenza vaccine by their treating oncologist/oncological team. Their oncology team will also determine that the patient’s participation in the study will not impact their clinical care or participation in other clinical trials
Exclusion Criteria
- HEALTHY PARTICIPANTS: Complete blood count (CBC) with differential, complete metabolic panel, anti-cytomegalovirus (CMV) immunoglobulin (Ig) G and IgM, and/or anti-Epstein-Barr virus (EBV) antibody panel values outside of the Yale Department of Laboratory Medicine normal reference ranges and deemed clinically significant by the principal investigator (PI) at the time of screening
- HEALTHY PARTICIPANTS: Positive result for anti-HIV 1/2 antibody at the time of screening
- HEALTHY PARTICIPANTS: Prior receipt of a current seasonal influenza vaccine (for the season of participation)
- HEALTHY PARTICIPANTS: History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein)
- HEALTHY PARTICIPANTS: History of severe reactions to vaccines
- HEALTHY PARTICIPANTS: Use of an oral glucocorticoid within the past 30 days
- HEALTHY PARTICIPANTS: Receipt of a live-attenuated vaccine within the past 3 months
- HEALTHY PARTICIPANTS: Receipt of any experimental vaccine
- HEALTHY PARTICIPANTS: Receipt of any other type of vaccine (non-live and non-experimental, e.g., tetanus, diphtheria, and pertussis [TDaP]) within the past 3 months
- HEALTHY PARTICIPANTS: Planned vaccination before day 100 after study vaccination
- HEALTHY PARTICIPANTS: Current or recent use (within the past 90 days) of immunoglobulin therapy
- HEALTHY PARTICIPANTS: Surgery within the past 8 weeks, or planned surgery before day 28
- HEALTHY PARTICIPANTS: Current (within the past 30 days) treatment for active malignancy
- HEALTHY PARTICIPANTS: Cancer chemotherapy in the past 2 years
- HEALTHY PARTICIPANTS: Administration of any blood products within 90 days of the screening, or planned administration before day 100
- HEALTHY PARTICIPANTS: History of parasitic, amebic, fungal, or mycobacterial infections within the past 1 year, with the exception of tinea pedis and onychomycosis
- HEALTHY PARTICIPANTS: History of autoimmune or autoinflammatory disease * In particular skin-related (i.e. psoriasis, lichen planus, lupus, neutrophilic dermatoses, atopic dermatitis)
- HEALTHY PARTICIPANTS: History of keloids
- HEALTHY PARTICIPANTS: History of a bleeding disorder
- HEALTHY PARTICIPANTS: Current use (within the past 30 days) of illicit drugs (per subject report), with the exception of marijuana
- HEALTHY PARTICIPANTS: Current alcohol use disorders (criteria per Diagnostic and Statistical Manual of Mental Disorders, fifth edition), within the past 30 days
- HEALTHY PARTICIPANTS: Serious, ongoing, uncontrolled infection within the past 30 days as per the judgement of the PI
- HEALTHY PARTICIPANTS: History of Guillain-Barre syndrome (GBS)
- HEALTHY PARTICIPANTS: Body mass index (BMI) ≥ 30
- HEALTHY PARTICIPANTS: Known or suspected immunodeficiency within 1 year, including documented HIV infection
- HEALTHY PARTICIPANTS: Pregnancy or planning to become pregnant during the study period. (Women of childbearing potential must have a negative urine or serum pregnancy test at screening.)
- HEALTHY PARTICIPANTS: Presence of conditions that, in the judgment of the PI, may put the individual at undue risk or compromise the scientific objectives of the study
- HEALTHY PARTICIPANTS: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the PI. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the PI
- NON-HEALTHY (CANCER) PARTICIPANTS: CBC with differential, complete metabolic panel, anti-CMV immunoglobulin (Ig) G and IgM, and/or anti-Epstein-Barr virus (EBV) antibody panel values outside of the Yale Department of Laboratory Medicine normal reference ranges and deemed clinically significant by the PI at the time of screening
- NON-HEALTHY (CANCER) PARTICIPANTS: Positive result for hepatitis B/C, tuberculosis, or anti-HIV 1/2 antibody at the time of screening
- NON-HEALTHY (CANCER) PARTICIPANTS: Prior receipt of a current seasonal influenza vaccine (for the season of participation) within the past 3 months
- NON-HEALTHY (CANCER) PARTICIPANTS: History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein)
- NON-HEALTHY (CANCER) PARTICIPANTS: History of severe reactions to vaccines
- NON-HEALTHY (CANCER) PARTICIPANTS: Active (episodes in the last year) autoimmune disease, such as but not limited to, vitiligo, hypothyroidism, multiple sclerosis, scleroderma, rheumatoid arthritis, and Grave’s disease
- NON-HEALTHY (CANCER) PARTICIPANTS: History of keloids
- NON-HEALTHY (CANCER) PARTICIPANTS: History of a bleeding disorder
- NON-HEALTHY (CANCER) PARTICIPANTS: Current use (within the past 30 days) of illicit drugs (per subject report), with the exception of marijuana
- NON-HEALTHY (CANCER) PARTICIPANTS: Current alcohol use disorders (criteria per Diagnostic and Statistical Manual of Mental Disorders, fifth edition), within the past 30 days
- NON-HEALTHY (CANCER) PARTICIPANTS: Serious, ongoing, uncontrolled infection within the past 30 days as per the judgement of the PI
- NON-HEALTHY (CANCER) PARTICIPANTS: History of Guillain-Barre syndrome (GBS)
- NON-HEALTHY (CANCER) PARTICIPANTS: Pregnancy or planning to become pregnant during the study period. (Women of childbearing potential must have a negative urine or serum pregnancy test at screening.)
- NON-HEALTHY (CANCER) PARTICIPANTS: Presence of conditions that, in the judgment of the PI, may put the individual at undue risk or compromise the scientific objectives of the study
- NON-HEALTHY (CANCER) PARTICIPANTS: Co-enrollment in other trials is allowed, so that participants can consider other trials with potentially life-saving cancer therapies. Study staff should still be notified of co-enrollment to any other protocol
Additional locations may be listed on ClinicalTrials.gov for NCT06067555.
Locations matching your search criteria
United States
Connecticut
New Haven
PRIMARY OBJECTIVE:
I. Identify baseline correlates of the peripheral immune response to an intradermally delivered seasonal influenza vaccine in healthy individuals.
SECONDARY OBJECTIVE:
I. Validate the established relationship of baseline biomarkers (CD38+ CD20+ B cell frequencies and/or transcriptomic signatures) and post-vaccination biomarkers (plasmablast cell frequencies and/or transcriptomic signatures) with antibody titer response to vaccination, as measured by microneutralization titers at day 0 and day 28.
EXPLORATORY OBJECTIVES:
I. Identify baseline (both pre- and post-vaccination) predictors of antitumor response or immune related adverse event development in the skin, blood, and microbiome of cancer patients about to undergo immune checkpoint
inhibitor therapy.
II. Characterize the dynamic (spatial and temporal) immune response to intradermal vaccination and how this relates to the systemic immune response and persistent vaccine-specific immunity.
III. Demonstrate robust immunization through intradermal vaccination as compared to intramuscular vaccination controls.
IV. Identify correlates of local (skin) immune responses to the severity of injection site reaction.
V. Relate baseline stool and skin microbiota to immunogenicity and identify changes in microbiota to vaccination.
VI. Integrate genetic variation and epigenetic information (chromatin conformation change, deoxyribonucleic acid [DNA] methylation) into quantitative trait loci as these relate to vaccine responses.
VII. Assess the impact of stromal cells (keratinocyte, fibroblast) on vaccine-induced innate immune responses.
OUTLINE:
PILOT SEASON (2024-2025): Patients are randomized to 1 of 9 cohorts.
COHORT I (IM-CONTROL): Patients receive seasonal influenza vaccine with Fluzone trivalent or quadrivalent vaccine IM and may optionally undergo an injection site skin punch biopsy on day 0. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT II (SALINE [SAL]-2HOUR [H]): Patients receive saline vaccine IM on day 0 and undergo an injection site skin punch biopsy at 2 hours after vaccination. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT III (SAL-6H): Patients receive saline vaccine IM on day 0 and undergo an injection site skin punch biopsy at 6 hours after vaccination. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT IV (SAL-DAY [D]1): Patients receive saline vaccine IM on day 0 and undergo an injection site skin punch biopsy on day 1. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT V (ID-2H): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo an injection site skin punch biopsy at 2 hours after vaccination. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT VI (ID-6H): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo an injection site skin punch biopsy at 6 hours after vaccination. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT VII (ID-D1): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo an injection site skin punch biopsy on day 1. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT VIII (ID-D3): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo an injection site skin punch biopsy on day 3. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT IX (ID-D28): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo an injection site skin biopsy on day 28. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
After completion of study treatment, patients who have not yet had vaccination site biopsies are followed up at days 1, 3, 7, and 28, then all patients are followed up on days 70, 100, and optionally on days 240, and 365.
HEALTHY PARTICIPANTS SEASON (2025-2026): Patients are randomized to 1 of 7 cohorts.
COHORT I (IM-CONTROL): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine IM and may optionally undergo injection site skin punch biopsy on day 0. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT II (ID-D7): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 7. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT III (ID-D28): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 28. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT IV (ID-D70): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 70. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT V (ID-D180): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 180. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT VI (ID-270): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 270. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
COHORT VII (ID-D365): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo injection site skin punch biopsy on day 365. Patients also undergo skin swab, nasal swab, and blood sample collection throughout the study. Additionally, patients may undergo skin biopsy at baseline.
After completion of study treatment, patients are followed up at days 1, 3, 7, 28, 70, 180, 270, and 365. Follow up on days 1 and 3 are optional for IM control patients.
CANCER PARTICIPANTS SEASON (2025-2026): Patients are randomized to 1 of 2 arms. Patients randomized to the ID arm may opt into the IM arm.
ARM I (ID-immune checkpoint inhibitor [ICI]): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine ID on day 0 and undergo skin punch biopsy of contralateral arm on day 0. Patients undergo injection site skin punch biopsy on day 3. Additionally, patients undergo skin swab, nasal swab, and blood sample collection and optional skin biopsies throughout the study.
ARM II (IM-ICI): Patients receive seasonal influenza vaccination with Fluzone trivalent or quadrivalent vaccine IM and undergo skin biopsy of contralateral arm on day 0. Additionally, patients undergo skin swab, nasal swab, and blood sample collection and optional skin biopsies throughout the study.
After completion of study treatment, patients are followed up at days 1 (optional) and 3, at ICI cycle 1 (day 7), cycle 2 (days 28-35), with immune-related adverse events (irAE) and at non-irAE occurrences (day 180).
Trial PhasePhase O
Trial Typebasic science
Lead OrganizationYale University
Principal InvestigatorAndrew Johnston
- Primary ID2000035891
- Secondary IDsNCI-2025-08520
- ClinicalTrials.gov IDNCT06067555