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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Fluzone® Quadrivalent, Fluzone Quadrivalent, Fluzone Intradermal, MicronJet, MicronJet device for intradermal vaccination?

Research shows that the Fluzone Intradermal vaccine is safe and produces a strong immune response in adults aged 18-64, similar to traditional flu shots. It uses a smaller needle, which may make it more acceptable to people who are hesitant about vaccines. ^{1 2 3 4 5}

Is the intradermal flu vaccine safe for humans?

The intradermal flu vaccine, including versions like Fluzone Intradermal and MicronJet, has been shown to be safe in adults, with studies indicating it is well-tolerated and comparable in safety to traditional flu shots. It has also been used safely in pregnant women, according to a global pregnancy registry. ^{1 2 4 6 7}

How is the Fluzone® Quadrivalent intradermal flu vaccine treatment different from other flu vaccines?

The Fluzone® Quadrivalent intradermal flu vaccine is unique because it uses a smaller needle and delivers the vaccine just under the skin (intradermally) rather than into the muscle (intramuscularly), which can make it more acceptable to patients. It also contains a lower amount of antigen per strain compared to traditional flu vaccines, which may help increase vaccination coverage among adults aged 18-64. ^{1 2 4 5 8}

Research Team

Andrew Johnston

Principal Investigator

Yale University

Eligibility Criteria

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

In good general health as evidenced by medical history

Able to proficiently speak, read, and write English

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18-64 years of age. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Fluzone(®) Intradermal vaccine: a promising new chance to increase the acceptability of influenza vaccination in adults. [2011]

3. Netherlands 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. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Acceptability of fluzone intradermal vaccine to patients and vaccine administrators. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Fluzone® Intradermal Quadrivalent Influenza Vaccine. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview. [2018]