Influenza Vaccine for Flu

Overseen By Sokratis Apostolidis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants

Disqualifiers: Febrile illness, Active malignancy, 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

Duration: 1 day

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand the immune system's response to the flu vaccine (influenza vaccination). Researchers will administer a standard flu shot to adults and then analyze their blood to study lymphocytes, the body's defense cells. The trial is open to adults who need a flu shot and do not have a current fever or cancer, have not recently donated blood, and have not received a flu shot in the past six months. As a Phase 4 trial, this research explores how the already FDA-approved and effective flu vaccine benefits more patients.

Will I have to stop taking my current medications?

The trial excludes people using immunosuppressing medications, so if you are on these, you would need to stop taking them to participate.

What is the safety track record for the influenza vaccination?

Research has shown that the flu vaccine is generally safe for most people, with serious side effects being rare. For instance, less than 1% of individuals who received the Flucelvax flu shot reported serious health issues within 28 days.

One study suggested a very small increase in the risk of Guillain-Barré Syndrome (GBS), a rare nerve condition, occurring in only 1-2 cases per million flu shots administered.

Most people experience only mild effects, such as a sore arm, fatigue, or a low fever. If a severe allergic reaction occurs, such as hives or difficulty breathing, immediate medical attention is crucial. Overall, the flu vaccine is well-tolerated and has a strong safety record. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike other treatments for influenza, which typically involve antiviral medications, this approach focuses on preventive vaccination using a seasonal quadrivalent inactivated influenza vaccine. This vaccine is unique because it targets four different flu virus strains, offering broader protection compared to traditional trivalent vaccines that cover only three strains. Researchers are excited about this treatment as it may enhance the immune response and provide better protection against influenza outbreaks, potentially reducing the need for antiviral drugs post-infection.

What is the effectiveness track record for the influenza vaccination?

Research shows that flu vaccines reduce the risk of illness from the flu. Studies indicate that the vaccine lowers the chances of serious flu complications, such as hospitalization. For instance, a review of several studies found that the vaccine reduces the risk of dying from the flu, even for individuals with other health issues. Additionally, research on adults with weakened immune systems showed the vaccine was 32% effective in preventing the flu. Although the vaccine's effectiveness can vary each year, widespread vaccination can reduce flu cases by up to 60%. This evidence supports the importance of getting a flu shot annually to protect against the flu. ^{6 7 8 9 10}

Who Is on the Research Team?

E.John Wherry, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults who can consent and need a flu shot as part of their regular health care. It's not for those with a fever, cancer, on drugs that suppress the immune system, who've donated blood recently or had a flu shot in the last 6 months, or have allergies to flu vaccines.

Inclusion Criteria

I live at home, can make my own decisions, and need a flu shot.

Exclusion Criteria

You have donated blood in the last 60 days.

I have received the flu vaccine in the last 6 months.

I currently have cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one intramuscular dose of seasonal quadrivalent inactivated influenza vaccine

1 day

1 visit (in-person)

Follow-up

Participants have peripheral blood drawn at pre-defined intervals to study lymphocyte responses

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Influenza vaccination

Trial Overview The study involves giving participants an influenza vaccine and then taking samples of their blood at set times afterwards to analyze how their immune cells respond to the vaccination.

How Is the Trial Designed?

Group I: Influenza vaccination cohort Experimental Treatment 1 Intervention

Adults will receive one intramuscular dose of seasonal quadrivalent inactivated influenza vaccine, as indicated for standard of care.

Influenza vaccination is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in United States as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in Canada as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in Japan as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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 high-dose quadrivalent influenza vaccine (QIV-HD) was approved for individuals 65 years and older, and a review of 2,122 adverse event reports showed that 95.1% were non-serious, aligning with findings from prelicensure trials.

No new safety concerns were identified, with the most common serious events being Guillain-Barré syndrome and local reactions, suggesting that QIV-HD is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Woo, EJ., Moro, PL.[2022]

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 AdimFlu-S showed strong immunogenicity in a study of 174 healthy children aged 3 to 17, achieving high seroprotection rates above 96.4% for all vaccine strains.

The vaccine was well tolerated with no serious adverse events reported over a 6-month follow-up period, indicating it is a safe option for improving protection against different influenza B lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. Chang, CY., Cho, CY., Lai, CC., et al.[2021]

In a pilot study involving 385 children and adolescents, the most common adverse event following the Fluenz Tetra nasal vaccine was nasal congestion, reported by 43.4% of participants, indicating that while side effects occurred, they were generally mild.

No serious adverse events or hospitalizations were reported, suggesting that the Fluenz Tetra vaccine is safe for use in children, with no significant safety concerns identified during the 2014/2015 influenza season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Quadrivalent Live Attenuated Influenza Vaccine (QLAIV) in Children and Adolescents: A Pilot Prospective Cohort Study in England. McNaughton, R., Lynn, E., Osborne, V., et al.[2018]

A new active surveillance system called SICOVA was developed in Mexico to monitor adverse events (AEs) following quadrivalent influenza vaccination, involving 2013 participants over three influenza seasons.

The overall adverse event rate was 9.09%, with most AEs being mild and not requiring medical visits, confirming the established safety profile of the Fluzone® Quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system. Betancourt-Cravioto, M., Cervantes-Powell, P., Tapia-Conyer, R., et al.[2022]

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]

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]

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]

Citations

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CDC Seasonal Flu Vaccine Effectiveness Studies Tables showing preliminary flu vaccine effectiveness data for the 2023-2024 season. ... Learn about flu vaccine effectiveness estimates from past ...

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

Influenza vaccine outcomes: a meta-analysis revealing ... Influenza vaccination was effective in reducing the mortality risk for all influenza virus infections despite the patient's comorbidities; for ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMsa2514268

Updated Evidence for Covid-19, RSV, and Influenza ... Among immunocompromised adults, one multicenter U.S. case–control study showed an influenza vaccine effectiveness of 32% (95% CI, 7 to 50) ...

4. 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.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836422

Estimated Burden of Influenza and Direct and Indirect ... When vaccine effectiveness was higher (60%), cases could be almost eliminated when only approximately 56% of the population was vaccinated in ...

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

Influenza (Flu) Vaccine Safety When there has been an increased risk, it has been in the range of 1-2 additional GBS cases per million flu vaccine doses administered. The data ...

7. 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 ( ...

8. cdc.gov cdc.gov/vaccines/hcp/current-vis/downloads/flu.pdf

Influenza (Flu) Vaccine (Inactivated or Recombinant) If you see signs of a severe allergic reaction (hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, or weakness), call 9- ...

9. fda.gov fda.gov/media/117022/download

Package Insert - AFLURIA QUADRIVALENT Serious adverse events (SAEs), including deaths, were collected for 180 days post-vaccination. Page 8. Package insert. Influenza Vaccine. STN BL 125254. 7.

10. 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 ...