Intradermal Influenza Vaccination

Sponsor

Yale University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06067555

Collaborator

Chan Zuckerberg Initiative Grant (Other)

250

Enrollment

Location

Arms

Anticipated Duration (Months)

9.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to characterize the immune response, both innate and adaptive, as well as locally and systemic, to intradermal (ID) vaccination in healthy individuals. The intervention involves intradermal administration of an FDA-approved intramuscular seasonal influenza vaccine, using an FDA-approved device MicronJet. Investigators will measure antibody titers, cell subtypes, and multi-omic profiles, by collecting skin and peripheral blood at baseline and at several time points after vaccination. The primary objective is to identify baseline correlates of immune response in the skin and peripheral blood to the seasonal influenza vaccine. The investigators secondary goals are to describe the inflammatory response in the skin over time.

Condition or Disease	Intervention/Treatment	Phase
Vaccine Reaction	Device: MicronJet Biological: Fluzone® Quadrivalent Biological: Fluzone® Quadrivalent	Early Phase 1

Detailed Description

Subjects will remain on study and may optionally repeat study visits (including vaccination) annually through the 2024-25 influenza season, with final study follow-up up to 1 year after vaccination. Sampling individual subjects across several influenza seasons will allow for monitoring of multi-season responses.

Skin and blood samples will be collected at various timepoints before and up to 365 days after vaccination to explore short and long-term effects of immunization. Skin microbe samples for metagenomic analysis will also be collected throughout the protocol. Subjects may optionally provide stool samples.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In the first year, an anticipated 25 participants will be enrolled (5 for each cohort), with expansion in subsequent years for a total of 50 per intradermal vaccination cohort (250 total anticipated).In the first year, an anticipated 25 participants will be enrolled (5 for each cohort), with expansion in subsequent years for a total of 50 per intradermal vaccination cohort (250 total anticipated).

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Characterization of Immune Response to Intradermal Influenza Vaccination

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intramuscular (IM) Control An intramuscular control group, from which no skin biopsies will be taken after vaccination. Only the intramuscular cohort will receive the vaccine via standard IM route in the deltoid region of the upper arm.	Biological: Fluzone® Quadrivalent Intramuscular injection of 0.3mL
Experimental: ID-6hour Participants receive intradermal vaccination in the upper arm and will have skin biopsy of vaccination site 6 hours after vaccine administration.	Device: MicronJet MicronJet 600 syringe will be used to administer intradermal flu vaccine injections Biological: Fluzone® Quadrivalent Intradermal injections of 0.3mL
Experimental: ID-1day Participants receive intradermal vaccination in the upper arm and will have skin biopsy of vaccination site 1 day after vaccine administration.	Device: MicronJet MicronJet 600 syringe will be used to administer intradermal flu vaccine injections Biological: Fluzone® Quadrivalent Intradermal injections of 0.3mL
Experimental: ID-3day Participants receive intradermal vaccination in the upper arm and will have skin biopsy of vaccination site 1 day after vaccine administration.	Device: MicronJet MicronJet 600 syringe will be used to administer intradermal flu vaccine injections Biological: Fluzone® Quadrivalent Intradermal injections of 0.3mL
Experimental: ID-28day Participants receive intradermal vaccination in the upper arm and will have skin biopsy of vaccination site 1 day after vaccine administration.	Device: MicronJet MicronJet 600 syringe will be used to administer intradermal flu vaccine injections Biological: Fluzone® Quadrivalent Intradermal injections of 0.3mL

Outcome Measures

Primary Outcome Measures

Change in antibody titer concentration to vaccination-Blood [Day 0 and Day 28]
Change in antibody titer to vaccination as measured by microneutralization titers at day 0 and day 28 will be correlated with biomarkers in the blood using generalized estimating equations.
Change in antibody titer concentration to vaccination-Skin [Day 0 and Day 28]
Change in antibody titer to vaccination as measured by microneutralization titers at day 0 and day 28 will be correlated with biomarkers in the skin at baseline using generalized estimating equations.

Secondary Outcome Measures

Change in antibody titer concentration to vaccination [Day 0 and Day 28]
Change in antibody titer response to vaccination as measured by microneutralization titers at day 0 and day 28 and its relationship with established baseline biomarkers (CD38+, CD20+, B cell, among others) and post-vaccination biomarkers (plasmablast, among others) in the blood will be correlated using generalized estimating equations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study, as well as have samples and data stored for future research.
Able to proficiently speak, read, and write English.
In good general health as evidenced by medical history

Exclusion Criteria:

CBC with differential, lymphocyte phenotyping with T, B, and natural killer cells (TBNK), 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.
Positive result for anti-HIV 1/2 antibody, antibody to hepatitis B surface antigen, or anti-hepatitis C virus antibody screening at the time of screening.
Prior receipt of a current seasonal influenza vaccine (for the season of participation).
History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein, latex).
History of severe reactions to vaccines.
Use of an oral glucocorticoid within the past 30 days.
Receipt of a live-attenuated vaccine within the past 3 months.
Receipt of any experimental vaccine.
Receipt of any other type of vaccine (non-live and non-experimental, e.g., tetanus, diphtheria, and pertussis [TDaP]) within the past 3 months.
Planned vaccination before day 100 after study vaccination.
Current or recent use (within the past 90 days) of immunoglobulin therapy.
Surgery within the past 8 weeks, or planned surgery before day 28.
Current (within the past 30 days) treatment for active malignancy.
Cancer chemotherapy in the past 2 years.
Administration of any blood products within 90 days of the screening, or planned administration before day 100.
History of parasitic, amebic, fungal, or mycobacterial infections within the past 1 year, with the exception of tinea pedis and onychomycosis.
History of autoimmune or autoinflammatory disease.

In particular skin-related (i.e. psoriasis, lichen planus, lupus, neutrophilic dermatoses, atopic dermatitis)

History of keloids
History of a bleeding disorder.
Current use (within the past 30 days) of illicit drugs (per subject report), with the exception of marijuana.
Current alcohol use disorders (criteria per Diagnostic and Statistical Manual of Mental Disorders, fifth edition), within the past 30 days.
Serious, ongoing, uncontrolled infection within the past 30 days as per the judgement of the PI.
History of Guillain-Barre syndrome (GBS).
BMI > 30.
Known or suspected immunodeficiency within 1 year, including documented HIV infection.
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.)
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.
Co-enrollment guidelines: 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Church Street Research Unit	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

Yale University
Chan Zuckerberg Initiative Grant

Investigators

Principal Investigator: Andrew Johnston, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yale University

ClinicalTrials.gov Identifier:

NCT06067555

Other Study ID Numbers:

2000035891

First Posted:

Oct 5, 2023

Last Update Posted:

Oct 5, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Study Results

No Results Posted as of Oct 5, 2023