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

Trial Summary

What is the purpose of this trial?

Cellular and humoral immune responses before and after seasonal influenza vaccination will be assessed. Each year, up to 100 participants will be enrolled. To study age-specific differences in immune responses, participants with various years of birth will be enrolled. The investigators hypothesize that humans with different birth years will mount antibody and cellular responses of different specificities following seasonal influenza vaccination.

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 data supports the effectiveness of the influenza vaccine treatment?

Research shows that quadrivalent influenza vaccines, like VaxigripTetra and Fluarix Quadrivalent, provide broader protection against the flu by including two A and two B virus strains. These vaccines have been shown to be safe and effective in preventing influenza, offering better protection than older trivalent vaccines by covering more virus strains. ^{1 2 3 4 5}

Is the influenza vaccine generally safe for humans?

The influenza vaccines, including various formulations like Fluzone Quadrivalent and Vaxigrip, have been widely used and studied for safety. They are generally considered safe, with common mild side effects such as injection-site reactions and headaches. Serious adverse reactions are rare, and extensive safety monitoring has shown no unexpected safety concerns. ^{1 4 6 7 8}

How is the influenza vaccine treatment different from other flu treatments?

The quadrivalent influenza vaccines (QIVs) are unique because they include two influenza A subtypes and two B type viruses, offering broader protection compared to trivalent vaccines (TIVs) that only cover one B strain. This reduces the risk of the vaccine not matching the dominant circulating B strain, providing more effective protection against the flu. ^{1 3 4 5 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands 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. [2019]

2. United States 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. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Quadrivalent inactivated influenza vaccine (VaxigripTetra™). [2018]

4. England 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. [2018]

5. New Zealand 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]

9. Netherlands 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. [2020]