Flu Vaccines for Influenza

Recruiting at 6 trial locations

Overseen By Richard Zimmerman, MD,MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must not be taking: Live vaccines, Non-live vaccines

Disqualifiers: Pregnancy, Guillain-Barré syndrome, 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

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

605 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you should not receive any live vaccines within 6 weeks or non-live vaccines within 2 weeks before joining the study.

What data supports the effectiveness of the treatment Flublok, Flucelvax, Flucelvax Quadrivalent, Flucelvax Tetra, Fluzone, Fluzone High-Dose, Fluzone High-Dose Quadrivalent, Influenza Virus Vaccine?

Research shows that high-dose versions of the Fluzone vaccine are effective in older adults, and Flucelvax Tetra has been recommended for healthcare workers due to its effectiveness against certain flu strains. Additionally, FluBlok is being tested for its ability to prevent flu infections, showing promise in ongoing trials. ^{1 2 3 4 5}

Is the flu vaccine safe for humans?

The flu vaccines, including Flublok, Flucelvax, and Fluzone, have been studied for safety in various age groups. Most reported side effects are mild and not serious, such as local reactions at the injection site. Serious side effects are rare, and ongoing safety monitoring supports their general safety in humans. ^{2 5 6 7 8}

How is the Fluzone High-Dose Quadrivalent vaccine different from other flu vaccines?

Fluzone High-Dose Quadrivalent is unique because it contains a higher amount of hemagglutinin, a protein that helps the body build immunity, compared to standard flu vaccines. This high-dose formulation is specifically designed to provide better protection for older adults, who may have weaker immune responses. ^{1 2 4 9 10}

What is the purpose of this trial?

This study is a randomized immunogenicity study in an enrolled cohort with active surveillance for influenza-like illness (ILI). During this study, participants will be randomly assigned to receive an approved cell culture-based influenza vaccine (Flucelvax) versus a licensed comparator influenza vaccine (Flublok or Fluzone). Blood samples from participants will be collected for measurement of biomarkers of immune response at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Participants will be asked if they wish to also provide saliva specimens at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Serum and peripheral blood mononuclear cells (PBMC) and plasma samples will be isolated from whole blood and tested for biomarkers of vaccine immunogenicity, and duration of antibody responses. Participants will receive electronic surveys via email or text message weekly asking about changes in health status and new ILI symptoms; those reporting illness may be asked to provide a respiratory swab for laboratory testing for influenza and other respiratory viruses and up to 2 additional blood draws (acute \[\<10 days after symptom onset\] and convalescent \[28 days after acute visit if lab-confirmed positive for influenza\]).

Research Team

Emmanuel B Walter, MD, MPH

Principal Investigator

Duke University

Eligibility Criteria

This trial is for individuals who want to help test the effectiveness of different flu vaccines: Flucelvax, Flublok, or Fluzone. Participants should be willing to provide blood and saliva samples over several months and report any symptoms of influenza-like illness.

Inclusion Criteria

Willing to provide written/electronic informed consent

I plan to get the flu vaccine as recommended.

I can commit to the full study period and attend all required follow-ups.

Exclusion Criteria

Any condition which, in the opinion of the investigators, may pose a health risk to the participant or interfere with the evaluation of the study objectives

I have had Guillain-Barré syndrome in the past.

I haven't had live vaccines in 6 weeks or non-live vaccines in 2 weeks before joining this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an influenza vaccine (Flucelvax, Flublok, or Fluzone) and provide blood samples for biomarker measurement

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for immune response and influenza-like illness symptoms, with weekly electronic surveys and potential additional blood draws

24 weeks

Weekly electronic surveys, up to 2 additional blood draws if symptomatic

Treatment Details

Interventions

• Flublok
• Flucelvax
• Fluzone

Trial Overview The study compares three approved flu vaccines by measuring immune responses in participants. It involves random assignment to one vaccine type, regular health surveys, and collection of blood/saliva at specific times to assess immunogenicity.

Participant Groups

Group I: Flucelvax (ccIIV4) Experimental Treatment 1 Intervention

Participants will receive Flucelvax (ccIIV4) at Visit 1.

Group II: Flublok (RIV) or Fluzone (IIV) Experimental Treatment 1 Intervention

Participants will receive Flublok (RIV) or Fluzone (IIV) at Visit 1.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

VA Medical Center-Cleveland

Collaborator

Trials

1

Recruited

610+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

VA Northeast Ohio Health Care

Collaborator

Trials

2

Recruited

1,100+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

Findings from Research

In a study involving 2670 healthy adults aged 65 and older, the quadrivalent high-dose influenza vaccine (IIV4-HD) demonstrated non-inferior immunogenicity compared to the licensed trivalent high-dose vaccine (IIV3-HD) for all four influenza strains.

IIV4-HD showed superior immune responses for both B strains compared to IIV3-HD that did not contain the same B-lineage strain, while maintaining a similar safety profile, indicating it is a more effective option without added safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. Chang, LJ., Meng, Y., Janosczyk, H., 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 high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

In a study involving 741 healthcare workers, the cell-based quadrivalent vaccine Flucelvax Tetra was found to have a high safety profile, with 99.8% of reported adverse events classified as not serious.

Out of 430 adverse events following immunization, only one was serious, and causality assessment indicated it was not linked to the vaccine, suggesting that Flucelvax Tetra is safe for use in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. Stefanizzi, P., De Nitto, S., Spinelli, G., et al.[2021]

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 recombinant hemagglutinin quadrivalent influenza vaccine (RIV4) was approved for use in individuals 18 years and older, showing a safety profile similar to standard-dose vaccines, with 95% of reported adverse events being non-serious.

Among the serious adverse events reported, there were 10 cases of Guillain-Barré syndrome, highlighting the importance of ongoing safety monitoring, although the overall incidence of serious reactions appears low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of quadrivalent recombinant influenza vaccine: Reports to the vaccine adverse event reporting system. Woo, EJ., Moro, PL.[2021]

Fluzone® High Dose, approved by the FDA for individuals 65 and older, contains four times more hemagglutinin than standard vaccines, leading to a stronger immune response against influenza.

A recent randomized controlled trial showed that this high-dose vaccine maintains a favorable safety profile while enhancing immunologic response, supporting its use in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine. Sullivan, SJ., Jacobson, R., Poland, GA.[2010]

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]

References

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

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

FluBlok, a recombinant influenza vaccine. [2017]

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

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. [2021]

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

Three seasons of enhanced safety surveillance of a cell culture-based quadrivalent influenza vaccine. [2023]

7. United States 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. [2022]

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

Postmarketing safety surveillance of quadrivalent recombinant influenza vaccine: Reports to the vaccine adverse event reporting system. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine. [2010]

10. New Zealand 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. [2018]