A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

NCT03734237 | Active Not Recruiting Phase 4 Results DMC FDA Drug

• 2 other identifiers: IDCRP-120AAI1201200007000
• Study Type: interventional
• Target: 15,448
• Locations: 1 country
• Sites: 9

Brief Summary

A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. Eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019, 2019-2020, 2020-2021, and 2021-2022).

Conditions

Influenza; Influenza-like Illness; Influenza Vaccines

Keywords

Influenza vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Laboratory Confirmed Influenza

  Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

  Onset > 13 days after vaccination up to 1 year

Secondary Outcomes (4)

• Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains.

  Baseline to 21-35 days post vaccine

• Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine.

  Baseline to 21-35 days post vaccine

• Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine.

  Baseline to 21-35 days post vaccine

• Number of Participants With Influenza-Like Illness

  Onset > 13 days after vaccination up to 1 year

Other Outcomes (2)

• Number of Participants With SARS-CoV-2 and Influenza Co-Infection

  Onset > 13 days after influenza vaccination up until one year

• Symptom Severity of SARS CoV2

  onset >13 days after Influenza vaccination up to 1 year

Study Arms (3)

Egg based influenza vaccines

ACTIVE COMPARATOR

Quadrivalent egg-based vaccines, which contain an inactivated form of the virus. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. All egg-based vaccines are FDA licensed for use in the United States.

Biological: Egg based influenza vaccines

Recombinant influenza vaccines

ACTIVE COMPARATOR

FluBlok, recombinant HA influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flublok Quadrivalent is a quadrivalent recombinant influenza vaccine that has been licensed by the FDA for use in the United States.

Biological: Recombinant influenza vaccines

Cell-culture based influenza vaccines

ACTIVE COMPARATOR

Flucelvax, Madin-Darby canine kidney (MDCK)-cell-culture based inactivated influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flucelvax quadrivalent, the only cell-based flu vaccine FDA licensed for use in the United States.

Biological: Cell-culture based influenza vaccines

Interventions

Cell-culture based influenza vaccines BIOLOGICAL

Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.

Cell-culture based influenza vaccines

Egg based influenza vaccines BIOLOGICAL

Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.

Egg based influenza vaccines

Recombinant influenza vaccines BIOLOGICAL

Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.

Recombinant influenza vaccines

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible for care in Department of Defense medical facilities (Defense Enrollment Eligibility Reporting System eligible)
• ≥18 years of age.
• At a participating Military Treatment Facility site for the purpose of receiving a seasonal (2018-2019, 2019-2020,2020-2021, 2021-2022) influenza vaccination.
• Able to speak English and able to provide informed consent
• Able to receive and respond to texts and/or emails, or a military recruit

You may not qualify if:

• Adults intending to receive or who have received the current seasons FluMist Vaccine (LAIV)
• Adults who have already received a flu vaccine within the current season
• Individual who cannot receive a flu vaccine or standard dosing due to another medical condition
• Allergic to gentamicin, polymyxin and/or neomycin

Sponsors & Collaborators

• Food and Drug Administration (FDA): collaborator
• US Department of Defense Armed Forces Health Surveillance Center: collaborator
• Naval Health Research Center: collaborator
• United States Air Force School of Aerospace Medicine: collaborator
• Uniformed Services University of the Health Sciences: collaborator
• Defense Health Agency: collaborator
• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (9)

Naval Medical Center San Diego

San Diego, California, 34800, United States

Location

United States Naval Academy

Annapolis, Maryland, 21402, United States

Location

USU

Bethesda, Maryland, 20307, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

Location

Womack Army Medical Center

Fort Bragg, North Carolina, 28310, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Lackland Airforce Base

San Antonio, Texas, 78243, United States

Location

Naval Medical Center Portsmouth

Portsmouth, Virginia, 23704, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

Location

Related Publications (9)

• Sanchez JL, Cooper MJ, Myers CA, Cummings JF, Vest KG, Russell KL, Sanchez JL, Hiser MJ, Gaydos CA. Respiratory Infections in the U.S. Military: Recent Experience and Control. Clin Microbiol Rev. 2015 Jul;28(3):743-800. doi: 10.1128/CMR.00039-14.

  PMID: 26085551 BACKGROUND

• Flannery B, Chung JR, Belongia EA, McLean HQ, Gaglani M, Murthy K, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Foust A, Sessions W, Berman L, Barnes JR, Spencer S, Fry AM. Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness - United States, February 2018. MMWR Morb Mortal Wkly Rep. 2018 Feb 16;67(6):180-185. doi: 10.15585/mmwr.mm6706a2.

  PMID: 29447141 BACKGROUND

• Zost SJ, Parkhouse K, Gumina ME, Kim K, Diaz Perez S, Wilson PC, Treanor JJ, Sant AJ, Cobey S, Hensley SE. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):12578-12583. doi: 10.1073/pnas.1712377114. Epub 2017 Nov 6.

  PMID: 29109276 BACKGROUND

• Wu NC, Zost SJ, Thompson AJ, Oyen D, Nycholat CM, McBride R, Paulson JC, Hensley SE, Wilson IA. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 2017 Oct 23;13(10):e1006682. doi: 10.1371/journal.ppat.1006682. eCollection 2017 Oct.

  PMID: 29059230 BACKGROUND

• Skowronski DM, Janjua NZ, De Serres G, Sabaiduc S, Eshaghi A, Dickinson JA, Fonseca K, Winter AL, Gubbay JB, Krajden M, Petric M, Charest H, Bastien N, Kwindt TL, Mahmud SM, Van Caeseele P, Li Y. Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS One. 2014 Mar 25;9(3):e92153. doi: 10.1371/journal.pone.0092153. eCollection 2014.

  PMID: 24667168 BACKGROUND

• Cobey S, Gouma S, Parkhouse K, Chambers BS, Ertl HC, Schmader KE, Halpin RA, Lin X, Stockwell TB, Das SR, Landon E, Tesic V, Youngster I, Pinsky BA, Wentworth DE, Hensley SE, Grad YH. Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013. Clin Infect Dis. 2018 Jul 18;67(3):327-333. doi: 10.1093/cid/ciy097.

  PMID: 29471464 BACKGROUND

• Wang W, Butler EN, Veguilla V, Vassell R, Thomas JT, Moos M Jr, Ye Z, Hancock K, Weiss CD. Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies. J Virol Methods. 2008 Nov;153(2):111-9. doi: 10.1016/j.jviromet.2008.07.015. Epub 2008 Sep 4.

  PMID: 18722473 BACKGROUND

• Wang W, Xie H, Ye Z, Vassell R, Weiss CD. Characterization of lentiviral pseudotypes with influenza H5N1 hemagglutinin and their performance in neutralization assays. J Virol Methods. 2010 May;165(2):305-10. doi: 10.1016/j.jviromet.2010.02.009. Epub 2010 Feb 11.

  PMID: 20153374 BACKGROUND

• Colombo RE, Richard SA, Schmidt K, Schofield C, Ganesan A, Campbell W, Hrncir D, Lalani T, Mende K, Markelz AE, Berjohn CM, Housel L, Becher D, Zell ER, Ewing D, Sundaram AK, Modi JR, Saperstein A, Tilley DH Jr, Williams A, McClenathan B, Collins L, Spooner C, Seshadri S, Fries A, Maves RC, Powers Iii JH, O'Connell RJ, Pollett SD, Simons MP, Coles CL, Burgess TH; PAIVED Study Group. Randomized Pragmatic Trial of the Comparative Effectiveness of Chicken Egg-Based Inactivated, Mammalian Cell Culture-Based Inactivated, and Recombinant Protein Quadrivalent Seasonal Influenza Vaccines in United States Military Health System Beneficiaries. Clin Infect Dis. 2025 Dec 24;81(5):e454-e463. doi: 10.1093/cid/ciaf503.

  PMID: 40973113 DERIVED

Related Links

• Influenza. Centers for Disease Control and Prevention

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Timothy Burgess, MD, MPH
• Organization: USUHS

timothy.burgess@usuhs.edu

(301) 295-9792

Study Officials

• Timothy Burgess, MD

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

• Rhonda Colombo, MD

  Infectious Diseases Clinical Research Program

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019,2019-2020, 2020-2021, and 2021-2022).

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 7, 2018
• Study Start: November 6, 2018
• Primary Completion: July 7, 2022
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 2, 2026
• Results First Posted: November 24, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)