Intradermal Flu Vaccine for Vaccine Reaction

Overseen By Andrew Johnston, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Glucocorticoids, Immunoglobulin therapy

Disqualifiers: HIV, Autoimmune diseases, Cancer, others

Compensation: Varies

Number of Visits: Unknown

249 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a flu vaccine administered intradermally affects the body's immune response. Researchers will compare different groups: those receiving the vaccine under the skin, those getting a standard muscle injection, and a control group receiving a saline injection. The main focus is to observe how the immune system reacts in the skin and blood over time. Individuals in generally good health, who haven't received the current flu vaccine and have no severe allergies to its components, might be suitable candidates for this study. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to be among the first to experience this new approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like oral glucocorticoids, immunoglobulin therapy, and recent vaccines may affect eligibility, so it's best to discuss your current medications with the study team.

What prior data suggests that this intradermal vaccination method is safe?

Research has shown that the Fluzone Quadrivalent vaccine is generally safe and is commonly used to protect individuals aged six months and older from the flu. Common side effects include itchiness, redness, swelling, and firmness at the injection site. These reactions are normal and usually mild.

In this trial, the vaccine is administered using a device called the MicronJet. Studies have found that this microneedle device is safe and effective. Many people prefer it because it is less invasive.

Since this trial is in the early stages, it primarily focuses on assessing the treatment's safety. These treatments have been used safely before, but it is always advisable to ask questions and understand any potential risks before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new method of delivering flu vaccines intradermally using the MicronJet device, rather than the traditional intramuscular injection. This approach might enhance the immune response by targeting the skin's immune cells more directly. Additionally, the trial investigates the body's reaction at various time points following vaccination, which could provide insights into optimizing flu vaccine efficacy and safety. By comparing intradermal administration to standard methods and placebo, researchers hope to uncover potential benefits and fine-tune vaccine delivery for better protection against influenza.

What evidence suggests that this trial's treatments could be effective for vaccine reaction?

Research has shown that the Fluzone® Quadrivalent intradermal vaccine, which participants in this trial may receive, can generate an immune response similar to traditional flu shots. Studies have found this vaccine effective in protecting against several flu strains. The MicronJet device, used to administer the vaccine just under the skin, is another component under study in this trial. It works well with smaller doses and still leads to a strong immune response. Clinical studies have demonstrated that tiny needles can be as effective as traditional methods and may offer a less painful and more efficient vaccination process. Both the vaccine and the device have been tested in various groups and have proven safe and effective in building immunity. ^{1 3 6 7 8}

Who Is on the Research Team?

Andrew Johnston

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Healthy individuals who can consent, follow study procedures, and are in good general health as per medical history. Excluded are pregnant women or those planning pregnancy, people with certain abnormal lab results, HIV/hepatitis infections, recent vaccines or blood products, surgery or severe infections within specific time frames, immunodeficiencies, other trial enrollments without PI approval, severe vaccine reactions history.

Inclusion Criteria

Provision of signed and dated informed consent form

Able to proficiently speak, read, and write English

In good general health as evidenced by medical history

Exclusion Criteria

I am currently receiving treatment for cancer.

You have had a condition where your immune system attacks your own body in the past.

I have received this season's flu vaccine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination and Initial Monitoring

Participants receive intradermal flu vaccination and undergo skin biopsies at various time points (2 hours, 6 hours, 1 day, 3 days, 28 days) to assess immune response.

4 weeks

Multiple visits for biopsies and sample collection

Follow-up

Participants are monitored for immune response and safety, with sample collection up to 365 days post-vaccination.

12 months

Periodic visits for sample collection

Annual Extension (optional)

Participants may optionally repeat study visits and vaccination annually through the 2025-26 influenza season.

Annually

What Are the Treatments Tested in This Trial?

Interventions

• Fluzone® Quadrivalent
• MicronJet

Trial Overview The study tests the immune response to an FDA-approved seasonal flu shot given intradermally using MicronJet. It measures how the body's defense system reacts both at the skin level and in the blood after vaccination by checking antibody levels and various cell types over time.

How Is the Trial Designed?

Group I: ID-6hour Experimental Treatment 2 Interventions

Participants receive intradermal flu vaccination in the upper arm and will have skin biopsy of vaccination site 6 hours after vaccine administration.

Group II: ID-3day Experimental Treatment 2 Interventions

Participants receive intradermal flu vaccination in the upper arm and will have skin biopsy of vaccination site 3 days after vaccine administration.

Group III: ID-2hour Experimental Treatment 2 Interventions

Participants receive intradermal flu vaccination in the upper arm and will have skin biopsy of vaccination site 2 hours after vaccine administration.

Group IV: ID-28day Experimental Treatment 2 Interventions

Participants receive intradermal flu vaccination in the upper arm and will have skin biopsy of vaccination site 3 days after vaccine administration.

Group V: ID-1day Experimental Treatment 2 Interventions

Participants receive intradermal flu vaccination in the upper arm and will have skin biopsy of vaccination site 1 day after vaccine administration.

Group VI: Intramuscular (IM) Control Active Control 1 Intervention

An intramuscular control group, from which no skin biopsies will be taken after vaccination. Only the intramuscular cohort will receive the flu vaccine via standard IM route in the deltoid region of the upper arm.

Group VII: Sal-1hour Placebo Group 2 Interventions

A control group in which bacteriostatic saline is injected intradermally in lieu of influenza vaccine. A skin biopsy will be taken from the "vaccination" site 1 day after administration.

Group VIII: Sal-2hour Placebo Group 2 Interventions

A control group in which bacteriostatic saline is injected intradermally in lieu of influenza vaccine. A skin biopsy will be taken from the "vaccination" site 2 hours after administration.

Group IX: Sal-6hour Placebo Group 2 Interventions

A control group in which bacteriostatic saline is injected intradermally in lieu of influenza vaccine. A skin biopsy will be taken from the "vaccination" site 6 hours after administration.

Fluzone® Quadrivalent is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fluzone Quadrivalent for:

• Active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine

Approved in European Union as Intanza for:

• Active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine

Approved in Canada as IDflu for:

• Active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Chan Zuckerberg Initiative Grant

Collaborator

Trials

1

Recruited

250+

Silicon Valley Community Foundation

Collaborator

Trials

6

Recruited

1,300+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Silicon Valley Community Foundation

Collaborator

Trials

6

Recruited

1,300+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Chan Zuckerberg Initiative

Collaborator

Trials

5

Recruited

1,900+

Published Research Related to This Trial

Intra-dermal (ID) influenza vaccines, like Fluzone® ID and Intanza®, show comparable or superior immunogenicity and safety compared to traditional intra-muscular vaccines, making them a promising option for improving vaccination coverage.

Advancements in ID vaccines, including options for alternative B strains and the potential for self-administration, enhance their appeal and could help address logistical challenges in influenza vaccination efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview. Bragazzi, NL., Orsi, A., Ansaldi, F., et al.[2018]

The Fluzone Intradermal (ID) vaccine was found to be as immunogenic as the standard intramuscular (IM) vaccine, showing no significant differences in antibody responses for all three viral strains tested.

While the ID vaccine had higher rates of local reactions like erythema and swelling compared to the IM vaccine, it was well-tolerated overall, with no serious adverse events reported, indicating it can be safely used for annual revaccination in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age. Gorse, GJ., Falsey, AR., Johnson, CM., et al.[2013]

Fluzone Intradermal Quadrivalent vaccine, introduced for the 2015-2016 season, includes two B-strain lineage viruses, enhancing its effectiveness against influenza by providing broader protection.

The vaccine utilizes a unique microinjection system, which not only improves the delivery method but also aims to alleviate logistical challenges for healthcare providers during vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluzone® Intradermal Quadrivalent Influenza Vaccine. Robertson, CA., Tsang, P., Landolfi, VA., et al.[2018]

The Fluzone® Quadrivalent (IIV4) vaccine was monitored for safety in pregnant women, with 239 exposure reports collected from August 2013 to September 2019, showing no new safety concerns related to maternal or neonatal outcomes.

Among the reported outcomes, over 85% of neonates were full-term births, and all infants with available information had normal APGAR scores, indicating that the vaccine is safe for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. Ledlie, S., Gandhi-Banga, S., Shrestha, A., et al.[2022]

Fluzone Intradermal, approved by the FDA in 2011, is the first influenza vaccine in the USA that uses a microinjection system for intradermal delivery, requiring a lower antigen content (9 µg) compared to conventional intramuscular vaccines (15 µg).

Clinical trials demonstrated that Fluzone Intradermal is safe and has immunogenicity comparable to traditional intramuscular vaccines, which may help improve influenza vaccination rates among adults aged 18 to 64.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluzone(®) Intradermal vaccine: a promising new chance to increase the acceptability of influenza vaccination in adults. Ansaldi, F., de Florentiis, D., Durando, P., et al.[2011]

In a study involving 367 participants, 67.8% chose the Fluzone Intradermal (ID) vaccine over the Intramuscular (IM) vaccine, indicating a strong preference for the ID method.

Participants reported significantly less preinjection anxiety and postinjection pain with the ID vaccine compared to the IM vaccine, with 99.6% satisfaction immediately after ID vaccination, highlighting its acceptability and potential benefits in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of fluzone intradermal vaccine to patients and vaccine administrators. Foy, JE., Hendriksz, T., Malouf, P., et al.[2013]

The MicronJet600, a novel intradermal delivery device, has shown significant dose-sparing effects and improved immunogenicity across various vaccines and diverse populations over 7 years of clinical experience.

Intradermal vaccination using the MicronJet600 is safe, effective, and preferred by subjects, indicating its potential to enhance vaccine delivery and acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future. Levin, Y., Kochba, E., Hung, I., et al.[2018]

The intradermal (ID) influenza vaccine demonstrated immune responses comparable to the intramuscular (IM) vaccine in a study of 4292 adults, meeting non-inferiority criteria for antibody levels against all three virus strains tested (H1N1, H3N2, and B).

While local injection site reactions were more frequent with the ID vaccine, they were mostly mild and transient, indicating that the ID vaccine is a well-tolerated alternative to the IM vaccine despite slightly higher rates of local discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18-64 years of age. Gorse, GJ., Falsey, AR., Fling, JA., et al.[2018]

Citations

1. fda.gov fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426679.pdf

Fluzone Intradermal Quadrivalent Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine. 23. • problems with your immune system as the immune response may be diminished.

2. cdc.gov cdc.gov/flu/vaccine-types/flu-zone.html

Fluzone High-Dose Seasonal Influenza Vaccine A randomized efficacy study published in the New England Journal of Medicine indicated that the trivalent high-dose vaccine was 24% more ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27457797/

Fluzone® Intradermal Quadrivalent Influenza Vaccine This literature review summarizes the history and mechanism of intradermal vaccination, discusses the clinical trial results supporting the immunogenicity ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02563093?tab=results

NCT02563093 | Study of Fluzone® Quadrivalent, ... Study of Fluzone® Quadrivalent, Fluzone® Intradermal Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines in Adults. ClinicalTrials.gov ID NCT02563093.

5. sciencedirect.com sciencedirect.com/science/article/pii/S016344532500132X

High-dose versus standard-dose influenza vaccine for ... Although high-dose influenza vaccine showed less frequency of clinical outcomes, data were not conclusive as few studies analysed clinical effectiveness.

6. fda.gov fda.gov/media/119856/download

Fluzone Quadrivalent Fluzone Quadrivalent is a vaccine that helps protect against influenza illness (flu). Fluzone Quadrivalent is for people who are 6 months of age and older.

7. vaccineshoppe.com vaccineshoppe.com/assets/pdf/Fluzone_Intradermal_Quadrivalent_Quick_Reference_Guide_MKT28892-1.pdf

Grab and Go! SAFETY INFORMATION. The most common local reactions to Fluzone Intradermal Quadrivalent vaccine include pruritus, erythema, swelling, and induration at the ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/influenza-virus-vaccine-intradermal-route-intramuscular-route/description/drg-20071452

Influenza virus vaccine (intradermal route, intramuscular ... Fluzone® Intradermal Quadrivalent and Fluzone® Quadrivalent come with a patient information leaflet. Read and follow these instructions ...