Influenza Vaccine for Flu

Overseen By Scott Hensley, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants, Chemotherapy, Steroids, others

Disqualifiers: Allergies, Immunosuppression, Cancer, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how people's immune systems respond to the seasonal influenza vaccine. Researchers aim to determine if birth year affects immune responses to the flu shot. The study uses a standard flu vaccine approved by the FDA and seeks generally healthy adults who haven't received a flu shot in the last two months. Participants should not have severe allergies to the vaccine or a history of severe reactions to flu shots. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs, steroids, or have received certain treatments recently, you may not be eligible to participate.

What is the safety track record for the seasonal influenza vaccine?

Previous studies have shown that the seasonal flu vaccine is very safe. Many recipients experience no side effects. When side effects occur, they are usually mild, such as pain or redness at the injection site, affecting about 55% and 18% of people, respectively.

Other mild reactions, like fever or feeling unwell, can also occur but typically resolve quickly. Serious side effects are rare, occurring in less than 1% of people. The FDA has approved the vaccine, indicating it has passed strict safety tests. Overall, the seasonal flu vaccine is well-tolerated and a safe choice for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

The influenza vaccine being studied is unique because it is a seasonal, inactivated, quadrivalent vaccine, meaning it is designed to protect against four different flu viruses. Unlike some flu vaccines that target only three strains, this quadrivalent vaccine aims to offer broader protection by covering an additional influenza B virus. Researchers are excited because this could potentially enhance the vaccine's effectiveness against the flu, offering more comprehensive protection during the flu season. This approach is particularly important as it considers the ever-evolving nature of flu viruses, aiming to reduce the overall impact of influenza outbreaks.

What is the effectiveness track record for the seasonal influenza vaccine?

Research has shown that the seasonal flu vaccine, which participants in this trial will receive, helps prevent serious flu-related complications. Studies indicate that the vaccine significantly lowers the risk of severe illness and hospitalizations, particularly for older adults and those with existing health conditions. For instance, one study found the vaccine to be about 51% effective in preventing hospital visits for certain flu types, such as influenza A(H3N2). Additionally, a review of multiple studies found that the flu shot reduced death rates linked to the H1N1 virus. Overall, the vaccine is a proven method to lessen the impact of the flu season. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Healthy adults aged 18 and older who are willing to follow the study procedures can join. They must not have had a flu shot in the last 2 months, any blood products or immunosuppressive treatments in the past 3 months, or cancer treatments within the last 3 years. People with certain allergies, immune conditions, or those on long-term steroids cannot participate.

Inclusion Criteria

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for all study visits

In good health based on self-reported medical conditions via an online survey

Exclusion Criteria

Known latex allergy

I received a flu shot within the last 2 months.

I don't have any health conditions that would make vaccination unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly

1 day

1 visit (in-person)

Follow-up

Participants are monitored for immune responses, including cellular and humoral responses, over several years

7 years

What Are the Treatments Tested in This Trial?

Interventions

• Seasonal influenza vaccine

Trial Overview The trial is studying how different age groups respond to the seasonal influenza vaccine by looking at their antibody and cellular responses. Up to 100 participants will be enrolled each year to see if birth year affects immunity after vaccination.

How Is the Trial Designed?

Group I: Influenza vaccination Experimental Treatment 1 Intervention

Adults will receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.

Seasonal influenza vaccine is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Seasonal influenza vaccine for:

• Prevention of influenza A and B virus infection

Approved in European Union as Seasonal influenza vaccine for:

• Prevention of influenza A and B virus infection

Approved in Canada as Seasonal influenza vaccine for:

• Prevention of influenza A and B virus infection

Approved in Japan as Seasonal influenza vaccine for:

• Prevention of influenza A and B virus infection

Approved in Switzerland as Seasonal influenza vaccine for:

• Prevention of influenza A and B virus infection

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

The Scripps Research Institute

Collaborator

Trials

34

Recruited

12,400+

Published Research Related to This Trial

The study involving 661 children aged 6 months to under 18 years demonstrated that the high-dose quadrivalent influenza vaccine (IIV4-HD) is safe, with no serious adverse events reported and similar rates of mild reactions compared to the standard-dose vaccine.

IIV4-HD at a dose of 60 µg significantly improved immune responses, particularly in younger children (6 months to <3 years), showing higher antibody titers against various influenza strains compared to the standard-dose vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Chang, LJ., Anderson, EJ., Jeanfreau, R., et al.[2021]

In a safety surveillance study of influenza vaccines during the 2017/18 season, adverse reactions (ARs) were reported by 2.9% of participants receiving the intradermal IIV3-ID vaccine, 1.4% for the standard IIV3 vaccine, and 2.1% for the quadrivalent IIV4 vaccine, indicating a generally low incidence of ARs across all vaccine types.

The most common ARs were injection-site reactions and headaches, and no significant changes in AR rates were observed compared to the previous season, suggesting consistent safety profiles for these vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced passive safety surveillance of three marketed influenza vaccines in the UK and the Republic of Ireland during the 2017/18 season. Gandhi-Banga, S., Chabanon, AL., Eymin, C., et al.[2020]

Vaxigrip, an inactivated influenza vaccine used since 1968, has proven effective in preventing over 37 million confirmed influenza cases and significantly reducing hospitalizations and deaths, highlighting its substantial public health impact.

The upcoming quadrivalent formulation of Vaxigrip (VaxigripTetra) maintains a similar safety and immunogenicity profile as the trivalent version while providing broader protection by including an additional B strain, enhancing its efficacy against influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trivalent, inactivated influenza vaccine (Vaxigrip®): summary of almost 50 years of experience and more than 1.8 billion doses distributed in over 120 countries. Haugh, M., Gresset-Bourgeois, V., Macabeo, B., et al.[2018]

VaxigripTetra™ (IIV4) is a quadrivalent influenza vaccine that has been shown to be immunogenic and well tolerated in individuals aged 3 years and older, based on phase III clinical trial results.

The addition of a second B strain in IIV4 enhances the immune response without compromising the response to the other three strains or affecting safety, potentially leading to greater protection against influenza-related illnesses compared to trivalent vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quadrivalent inactivated influenza vaccine (VaxigripTetra™). Gresset-Bourgeois, V., Leventhal, PS., Pepin, S., et al.[2018]

The 2019-20 seasonal influenza vaccines in the U.S. will include updated strains, specifically targeting A/Brisbane/02/2018 (H1N1), A/Kansas/14/2017 (H3N2), and B/Colorado/06/2017 (Victoria lineage), ensuring better protection against circulating viruses.

Routine annual vaccination is recommended for everyone aged 6 months and older, with specific updates on dosage volumes for certain vaccines, such as Afluria and Fluzone Quadrivalent, to enhance safety and efficacy in different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2019-20 Influenza Season. Grohskopf, LA., Alyanak, E., Broder, KR., et al.[2020]

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]

The quadrivalent influenza vaccine S-IIV4 demonstrated noninferior immunogenicity compared to the US-licensed C-IIV4 in a study involving 2,247 children aged 6-59 months, indicating it effectively stimulates the immune response against influenza strains.

S-IIV4 was associated with lower rates of fever (5.8%) compared to C-IIV4 (8.4%), suggesting improved safety in terms of febrile reactions, with no reports of febrile convulsions in either vaccine group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study. Statler, VA., Albano, FR., Airey, J., et al.[2019]

The quadrivalent influenza vaccine (IIV4) demonstrated a vaccine efficacy of approximately 51% against any influenza strain and 68% against vaccine-like strains in a study involving 5806 healthy children aged 6-35 months.

IIV4 was found to be safe, with a safety profile similar to that of placebo and other licensed vaccines, although it did have slightly more frequent injection-site reactions compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, immunogenicity, and safety of a quadrivalent inactivated influenza vaccine in children aged 6-35 months: A multi-season randomised placebo-controlled trial in the Northern and Southern Hemispheres. Pepin, S., Dupuy, M., Borja-Tabora, CFC., et al.[2020]

The D-QIV vaccine, which includes two A and two B influenza strains, has shown to be highly immunogenic in large trials involving healthy adults and children, meeting and exceeding vaccine licensure criteria.

D-QIV was well tolerated across all age groups and demonstrated superior immune responses against the additional B strain compared to traditional trivalent vaccines, potentially offering better protection against circulating influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inactivated quadrivalent split-virus seasonal influenza vaccine (Fluarix® quadrivalent): a review of its use in the prevention of disease caused by influenza A and B. McKeage, K.[2022]

Citations

1. cdc.gov cdc.gov/flu-vaccines-work/php/effectiveness-studies/index.html

CDC Seasonal Flu Vaccine Effectiveness Studies *2020-2021 flu vaccine effectiveness was not estimated due to low influenza virus circulation during the 2020-2021 flu season. A point estimate ...

2. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7406a2.htm

Interim Estimates of 2024–2025 Seasonal Influenza ... - CDC Effectiveness against influenza A(H3N2) was 51% (IVY) against influenza-associated hospitalization but was not statistically significant in the ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.01.30.25321421v3

Effectiveness of the Influenza Vaccine During the 2024- ... This study found that influenza vaccination of working-aged adults was associated with a higher risk of influenza during the 2024-2025 respiratory viral season.

4. fda.gov fda.gov/vaccines-blood-biologics/influenza-vaccine-composition-2025-2026-us-influenza-season

Influenza Vaccine Composition for the 2025-2026 U.S. ... Data and information on mid-season vaccine effectiveness for the 2024-2025 vaccines; and; Information on candidate vaccine virus strains for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11707602/

Influenza vaccine outcomes: a meta-analysis revealing ... Influenza vaccination significantly decreased the mortality OR associated with H1N1 infection (figure 4d, red bars) even 3 months after the ...

6. cdc.gov cdc.gov/vaccine-safety/vaccines/flu.html

Influenza (Flu) Vaccine Safety Many people who get an annual flu vaccine report no side effects at all. Most side effects reported after flu vaccination are mild and disappear ...

7. gskflu.com gskflu.com/fluarix/

FLUARIX (Influenza Vaccine) The most common (≥10%) solicited local adverse reactions with FLUARIX in adults were pain (55%) and redness (18%), and the most common systemic adverse ...

8. gskpro.com gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Fluarix/pdf/FLUARIX.PDF

1 FULL PRESCRIBING INFORMATION 1 INDICATIONS ... Vaccination with FLUARIX may not protect all susceptible individuals. 6. ADVERSE REACTIONS. The safety experience with FLUARIX QUADRIVALENT is relevant to ...

9. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-Flucelvax.pdf

Package Insert - Flucelvax Serious adverse events occurring within 28 days of any vaccination were reported in <1% of subjects (8 of 3345) who received FLUCELVAX, and in <1% of subjects ( ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9002594/

Adverse Events of Interest Following Influenza Vaccination ... Seasonal influenza vaccines are known to be associated with a range of adverse events of interest (AEIs), including minor ones like fever, malaise, and ...