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AzTrials

ImmunologyPhase 4NCT07910266

Impact of Egg-Based and Cell-Based Vaccine Platforms on Immune Responses to Repeated Influenza Vaccination

A Phase 4 study testing Egg-Based Inactivated Influenza Vaccine and Cell-Based Inactivated Influenza Vaccine in people with Immunology, run by University of Missouri-Columbia at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this clinical trial is to learn how different types of influenza (flu) vaccines affect the body's immune response over time. Researchers want to understand whether receiving egg-based flu vaccines, cell-based flu vaccines, or a combination of both influences how the immune system responds to future flu… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Immunology
What is being tested?
Egg-Based Inactivated Influenza Vaccine and Cell-Based Inactivated Influenza Vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
220 participants
Where
1 siteUnited States
Study dates
Oct 2026to Sep 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Did NOT receive a flu shot last year
  • Planning to get flu shot this year;
  • 18 years of age or older;
  • English speaking
  • Willing to be randomized to receive either FDA-approved cell-based or egg-based flu vaccination
  • Willing to get a second flu shot about 3 months after the first one

Who cannot join

  • Received a flu shot last year
  • Less than 18 years old
  • Not willing to be directed to get a certain type of vaccination
  • Not willing to get a flu vaccination or a second vaccination during the study period
  • Does not speak English
  • History of severe allergic reaction (e.g., anaphylaxis) following a previous influenza vaccine or to a component of the study vaccine.
  • Have a history of Guillain-Barré Syndrome within 6 weeks of a previous influenza vaccination.
  • Women who are pregnant or may be pregnant will not receive the second study vaccination

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Anna Zakrzewicz, PhD contact

573-882-3202

annazakrzewicz@umsystem.edu

Jane A McElroy, PhD contact

573-882-4993

mcelroyja@umsystem.edu

United States1 site, 1 recruiting

  • University of Missouri Systems

    Columbia, Missouri, 65212

    Anna Zakrzewicz, PhD, annazakrzewicz@health.missouri.edu

    Jane A McElroy, PhD, 573-882-4993, mcelroyja@umsystem.edu

    Recruiting

Other trials in United States

About this study

The goal of this clinical trial is to learn how different types of influenza (flu) vaccines affect the body's immune response over time. Researchers want to understand whether receiving egg-based flu vaccines, cell-based flu vaccines, or a combination of both influences how the immune system responds to future flu vaccinations.

The main questions this study aims to answer are:

Read more
  1. Does a person's previous flu vaccine type affect their immune response to a later flu vaccine?
  2. Do repeated vaccinations with the same vaccine platform or switching between vaccine platforms produce different antibody responses?
  3. How do different vaccination histories affect flu-specific immune cells and protection against different influenza strains?

Participants will be randomly assigned to receive one of four vaccine combinations:

  • Egg-based vaccine followed by egg-based vaccine
  • Egg-based vaccine followed by cell-based vaccine
  • Cell-based vaccine followed by cell-based vaccine
  • Cell-based vaccine followed by egg-based vaccine Researchers will compare immune responses among these groups.

Participants will:

  • Complete a baseline survey about demographics, vaccination history, medical history, and household information.
  • Receive a first seasonal influenza vaccination (egg-based or cell-based, depending on random assignment).
  • Provide blood samples before vaccination and several times afterward to measure immune responses.
  • Receive a second study influenza vaccination approximately 3 months after the first vaccination.
  • Continue providing blood samples after the second vaccination.
  • Complete brief follow-up surveys about health changes, additional vaccinations, and influenza-like illness during the study.

Blood samples will be collected up to eight times during each study year:

  1. Before or on the day of the first vaccination
  2. About 1 week after the first vaccination
  3. About 1 month after the first vaccination
  4. About 3 months after the first vaccination (the second vaccination will be given at this visit)
  5. About 1 week after the second vaccination
  6. About 1 month after the second vaccination
  7. About 3 months after the second vaccination
  8. About 6 months after the second vaccination

Participants may be observed for approximately 15 minutes after vaccination, consistent with routine vaccination practices.

Prior to the second vaccination, participants will be evaluated for any reasons that might make vaccination unsafe or require postponement. Participants who are able to become pregnant will complete a urine pregnancy test before the second vaccination. Participants who are pregnant or have a positive pregnancy test will not receive the second study vaccination but may continue study follow-up activities, including blood collection and surveys.

Participation in each study year lasts up to 10 months. Participants may choose to continue participating annually for up to 7 years.

Blood samples and related study data may be stored in a secure research biorepository for future studies related to infectious diseases, immunology, vaccine responses, and other health conditions. Stored samples will be coded to protect participant privacy, and identifying information will not be shared without appropriate approvals and participant authorization

Read the detailed description

Blood samples will be collected up to 8 times in the annual flu season starting in the fall:

  1. prior to or day of being vaccinated;
  2. about one week after being vaccinated;
  3. about one month after being vaccinated;
  4. about three months after being vaccinated and 2nd vaccination shot will be given on the same day as providing the 3-month blood sample. Following standard clinical practice, participants will be offered the opportunity to remain in the clinic for approximately 15 minutes after vaccination for observation. Observation is not a study-specific requirement but may be conducted consistent with routine vaccine administration practices at the clinical site.
  5. about one week after 2nd vaccination;
  6. about one month after 2nd vaccination;
  7. about three months after 2nd vaccination;
  8. about six months after 2nd vaccination

The egg-based inactivated trivalent (FluLaval) and cell-based inactivated trivalent (Flucelvax) vaccinations will be given. Participants will be randomized into one of 4 groups:

  1. Egg-based then 2nd shot Egg-based
  2. Egg-based then 2nd shot Cell-based
  3. Cell-based then 2nd shot Cell-based
  4. Cell-based then 2nd shot Egg-based Participants will receive a $20 Amazon e-gift card for each blood specimen collection completed.
Conditions
Immunology
Being tested
Egg-Based Inactivated Influenza Vaccine, Cell-Based Inactivated Influenza Vaccine
Keywords
Influenza vaccination, egg-based vaccine, cell-based vaccine
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Egg-Based Inactivated Influenza VaccineDrug

    Participants receive a licensed egg-based inactivated influenza vaccine at one or both study vaccination visits.

  • Cell-Based Inactivated Influenza VaccineDrug

    Participants receive a licensed cell-based inactivated influenza vaccine at one or both study vaccination visits.

Study groups in NCT07910266
Study groupRoleWhat they receive
Egg-Based → Egg-Based (E-E)ExperimentalE-E: Participants receive an egg-based inactivated influenza vaccine at the first vaccination and an egg-based inactivated influenza vaccine approximately 3 months later.
Receives: Drug: Egg-Based Inactivated Influenza Vaccine
Egg-Based → Cell-Based (E-C)ExperimentalParticipants receive an egg-based inactivated influenza vaccine at the first vaccination and a cell-based inactivated influenza vaccine approximately 3 months later.
Receives: Drug: Egg-Based Inactivated Influenza Vaccine; Drug: Cell-Based Inactivated Influenza Vaccine
Cell-Based → Cell-Based (C-C)ExperimentalParticipants receive a cell-based inactivated influenza vaccine at the first vaccination and a cell-based inactivated influenza vaccine approximately 3 months later.
Receives: Drug: Cell-Based Inactivated Influenza Vaccine
Cell-Based → Egg-Based (C-E)ExperimentalParticipants receive a cell-based inactivated influenza vaccine at the first vaccination and an egg-based inactivated influenza vaccine approximately 3 months later.
Receives: Drug: Egg-Based Inactivated Influenza Vaccine; Drug: Cell-Based Inactivated Influenza Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from Baseline in Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers at 1 Month After the Second Vaccination

    Hemagglutination inhibition (HAI) antibody titers against the prespecified influenza vaccine strains will be measured in serum samples using the HAI assay. Changes in HAI antibody geometric mean titers from baseline before the first vaccination to 1 month after the second vaccination will be compared among participants receiving four vaccination regimens: egg-egg, egg-cell, cell-egg, and cell-cell.

    Measured: Before the first vaccination and 1 month after the second vaccination.

Secondary outcomes (1)

  1. Change from Baseline in Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers at 1 Month After the First Vaccination

    Hemagglutination inhibition (HAI) antibody titers against the prespecified influenza vaccine strains will be measured in serum samples using the HAI assay. Changes in HAI antibody geometric mean titers from baseline before the first vaccination to 1 month after the first vaccination will be compared among participants in the four vaccination regimens, as appropriate to their assigned vaccination sequence.

    Measured: Before the first vaccination and 1 month after the first vaccination.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2026
  2. Study startOct 2026 (estimated)
  3. Primary completionFeb 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
220 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07910266
Sponsor's protocol ID
2136695
Status last verified
Oct 2026
First submitted
14 Oct 2026
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data supporting published study findings may be shared with qualified researchers upon reasonable request, subject to institutional approval and applicable data-sharing policies.

Publications

  • Stein AN, Thanataveerat A, McDermott KW, Dean A, Wall S, Pack C, Sullivan SG, McGovern I, Haag MDM. Estimated Relative Effectiveness and Public Health Impact of Cell-Based Versus Egg-Based Influenza Vaccines During the 2022-2023 Season in the United States. Influenza Other Respir Viruses. 2025 Nov;19(11):e70180. doi: 10.1111/irv.70180.

    PubMed 41185937

  • Rayens E, Ku JH, Sy LS, Qian L, Ackerson BK, Luo Y, Tubert JE, Lee GS, Modha PP, Park Y, Sun T, Anderson EJ, Tseng HF. Comparative Effectiveness of Cell-Based Versus Egg-Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-2023 Season Among Adults 18-64 Years. Influenza Other Respir Viruses. 2024 Dec;18(12):e70025. doi: 10.1111/irv.70025.

    PubMed 39696975

  • Stein AN, Mills CW, McGovern I, McDermott KW, Dean A, Bogdanov AN, Sullivan SG, Haag MDM. Relative Vaccine Effectiveness of Cell- vs Egg-Based Quadrivalent Influenza Vaccine Against Test-Confirmed Influenza Over 3 Seasons Between 2017 and 2020 in the United States. Open Forum Infect Dis. 2024 May 2;11(5):ofae175. doi: 10.1093/ofid/ofae175. eCollection 2024 May.

    PubMed 38698895

  • Boyce TG, Levine MZ, McClure DL, King JP, Flannery B, Nguyen HQ, Belongia EA. Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults. Hum Vaccin Immunother. 2024 Dec 31;20(1):2370087. doi: 10.1080/21645515.2024.2370087. Epub 2024 Jul 9.

    PubMed 38982712

  • Jordan K, Murchu EO, Comber L, Hawkshaw S, Marshall L, O'Neill M, Teljeur C, Harrington P, Carnahan A, Perez-Martin JJ, Robertson AH, Johansen K, Jonge J, Krause T, Nicolay N, Nohynek H, Pavlopoulou I, Pebody R, Penttinen P, Soler-Soneira M, Wichmann O, Ryan M. Systematic review of the efficacy, effectiveness and safety of cell-based seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals >/=18 years of age. Rev Med Virol. 2023 May;33(3):e2332. doi: 10.1002/rmv.2332. Epub 2022 Feb 8.

    PubMed 35137512

  • Coleman BL, Gutmanis I, McGovern I, Haag M. Effectiveness of Cell-Based Quadrivalent Seasonal Influenza Vaccine: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2023 Oct 17;11(10):1607. doi: 10.3390/vaccines11101607.

    PubMed 37897009

  • Puig-Barbera J, Tamames-Gomez S, Plans-Rubio P, Eiros-Bouza JM. Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022 Jan 12;19(2):818. doi: 10.3390/ijerph19020818.

    PubMed 35055642

  • Boikos C, Fischer L, O'Brien D, Vasey J, Sylvester GC, Mansi JA. Relative Effectiveness of the Cell-derived Inactivated Quadrivalent Influenza Vaccine Versus Egg-derived Inactivated Quadrivalent Influenza Vaccines in Preventing Influenza-related Medical Encounters During the 2018-2019 Influenza Season in the United States. Clin Infect Dis. 2021 Aug 2;73(3):e692-e698. doi: 10.1093/cid/ciaa1944.

    PubMed 33400775

  • Boikos C, Sylvester GC, Sampalis JS, Mansi JA. Relative Effectiveness of the Cell-Cultured Quadrivalent Influenza Vaccine Compared to Standard, Egg-derived Quadrivalent Influenza Vaccines in Preventing Influenza-like Illness in 2017-2018. Clin Infect Dis. 2020 Dec 17;71(10):e665-e671. doi: 10.1093/cid/ciaa371.

    PubMed 32253431

  • Izurieta HS, Chillarige Y, Kelman J, Wei Y, Lu Y, Xu W, Lu M, Pratt D, Chu S, Wernecke M, MaCurdy T, Forshee R. Relative Effectiveness of Cell-Cultured and Egg-Based Influenza Vaccines Among Elderly Persons in the United States, 2017-2018. J Infect Dis. 2019 Sep 13;220(8):1255-1264. doi: 10.1093/infdis/jiy716.

    PubMed 30561688

  • Bruxvoort KJ, Luo Y, Ackerson B, Tanenbaum HC, Sy LS, Gandhi A, Tseng HF. Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017-2018. Vaccine. 2019 Sep 16;37(39):5807-5811. doi: 10.1016/j.vaccine.2019.08.024. Epub 2019 Aug 22.

    PubMed 31445771

  • Gaglani M, Raiyani C, Murthy K, Smith M, da Graca B, Dubrocq G, Beeram M, Martin ET, Monto AS, Zimmerman RK, Nowalk MP, Kiniry E, Phillips CH, Nguyen HQ, King JP, Kim SS, Chung JR, Flannery B. Absolute and Relative Effectiveness of Cell Culture-Based and Egg-Based Quadrivalent Inactivated Influenza (Flu) Vaccine Products From the 2014-2015 to 2018-2019 Seasons, US Flu VE Network. Clin Infect Dis. 2026 Sep 2;83(2):289-302. doi: 10.1093/cid/ciaf579.

    PubMed 41102880

  • Stein AN, Thanataveerat A, McDermott K, Dean A, Wall S, Pack C, McGovern I, Sullivan SG, Haag M. Superior Effectiveness and Estimated Public Health Impact of Cell- Versus Egg-Based Influenza Vaccines in Children and Adults During the US 2023-2024 Season. Infect Dis Ther. 2025 Dec;14(12):2693-2718. doi: 10.1007/s40121-025-01230-2. Epub 2025 Oct 3.

    PubMed 41042449

  • Liu F, Gross FL, Joshi S, Gaglani M, Naleway AL, Murthy K, Groom HC, Wesley MG, Edwards LJ, Grant L, Kim SS, Sambhara S, Gangappa S, Tumpey T, Thompson MG, Fry AM, Flannery B, Dawood FS, Levine MZ. Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines. Nat Commun. 2024 Jan 4;15(1):254. doi: 10.1038/s41467-023-44551-x.

    PubMed 38177116

  • Imran M, Ortiz JR, McLean HQ, Fisher L, O'Brien D, Bonafede M, Mansi JA, Boikos C. Relative Effectiveness of Cell-Based Versus Egg-Based Quadrivalent Influenza Vaccines in Adults During the 2019-2020 Influenza Season in the United States. Open Forum Infect Dis. 2022 Oct 12;9(10):ofac532. doi: 10.1093/ofid/ofac532. eCollection 2022 Oct.

    PubMed 36320195

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Egg-Based Inactivated Influenza Vaccine and Cell-Based Inactivated Influenza Vaccine in people with Immunology, run by University of Missouri-Columbia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anna Zakrzewicz, PhD (573-882-3202, annazakrzewicz@umsystem.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline in Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers at 1 Month After the Second Vaccination (time frame: Before the first vaccination and 1 month after the second vaccination.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07910266, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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