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COVID -19Phase 4CIRV2NCT07287137

Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

A Phase 4 study testing Pfizer-BioNTech mRNA COVID-19 vaccine and Novavax recombinant protein vaccine in people with COVID -19 and COVID - 19, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

CIRV2 is a Phase IV randomized, open-label, trial of FDA-approved COVID-19 and/or influenza vaccines (no more than minimal risk) with longitudinal follow-up. In 2026 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine. Read more about this study

Who is it for?
Ages 18 to 79 yearsHealthy volunteers can take part
Conditions the study is for
COVID -19, COVID - 19, COVID 19
What is being tested?
Pfizer-BioNTech mRNA COVID-19 vaccine and Novavax recombinant protein vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
12 Nov 2025to 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 to 79 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 18-79 years old
  • Have a history of any of the following risk factors for severe COVID:
  • Current:
  • Age > 65 years old
  • Physical inactivity (defined as <150 mins of moderate activity per week or <75 mins of vigorous activity per week)
  • HIV with CD4 count ≥ 500 cells/ul
Show all 31Show fewer
  • Smoker
  • Obesity with BMI ≥ 30 and < 40
  • History of:
  • Asthma
  • Depression or other mood disorder
  • Schizophrenia spectrum disorder
  • Cerebrovascular disease
  • Heart failure
  • Coronary artery disease
  • Cardiomyopathy
  • Pulmonary embolism
  • Pulmonary hypertension
  • Cystic fibrosis
  • Bronchiectasis
  • Chronic obstructive pulmonary disease
  • Interstitial Lung Disease
  • Stage I or II chronic kidney disease (Stage 1 defined as normal GFR (> 90) but with other signs of kidney damage such as proteinuria or hematuria) (Stage 2 defined as having a glomerular filtration rate (GFR) of 60 - 89 ml/min/1.73m2)
  • Gestational diabetes
  • Type 1 diabetes with most recent HgbA1C < 7.5%
  • Type 2 diabetes with most recent HgbA1C < 7.5%
  • Liver disease without cirrhosis and with liver enzyme levels (AST and ALT) no greater than three times the upper limit of normal
  • Smoking
  • Military Health System beneficiary and DEERS eligible
  • Willing to be randomized to receive either the Novavax COVID-19 vaccine or the mRNA Pfizer-BioNTech COVID-19 vaccine
  • Will be able to return for a clinic visit in approximately 30 days, Day 150, and be able to follow-up online for the next 9 months.

Who cannot join

  • History of severe allergy or severe adverse reaction such as myocardial inflammation to any component of the mRNA COVID-19 vaccines or the Novavax recombinant COVID-19 vaccine
  • Received a COVID-19 vaccine in the last 3 months.
  • Tested positive for COVID-19 in the past 3 months.
  • Presence of fever, cough, chills, shortness of breath, runny nose, or sore throat today on day of screening/enrollment visit.
  • Active use of immune modulating medications.
  • Defined as active use of chronic immune modulating medications such as systemic corticosteroids at a dose equivalence of 20 mg prednisone or greater daily for over one month, chemotherapy, cytokine inhibitors, or agents that reduce T cell or B cell numbers or function.
Show all 17Show fewer
  • Diagnosed with immunocompromised stated.
  • Defined as: presence of a disease that is actively causing severe immune suppression or history of prior splenectomy (removal of spleen).
  • Diabetes with the most recent HgbA1C ≥ 7.5.
  • Stage III or greater chronic kidney disease
  • Defined as estimated glomerular filtration rate < 60 ml/min/1.73m2)
  • Obesity with a BMI ≥ 40
  • HIV with a CD4 cell count < 500 cells/ul
  • History of solid organ or bone marrow transplant.
  • Active malignancy
  • Defined as any cancer that is currently being treated or has shown evidence of progression within the past year.
  • Chronic liver disease with compensated or decompensated cirrhosis, or liver enzyme levels (AST or ALT) greater than three times the upper limit of normal.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20814

Other trials in United States

About this study

Official title: IDCRP-154: Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

CIRV2 is a Phase IV randomized, open-label, trial of FDA-approved COVID-19 and/or influenza vaccines (no more than minimal risk) with longitudinal follow-up. In 2026 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine.

Read the detailed description

The goal of the Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) study is to conduct, on a yearly basis, direct comparisons of immunogenicity and reactogenicity of the most recent versions of FDA-approved vaccines for COVID-19 and/or influenza. Studies will be conducted on individuals that are FDA eligible to receive these vaccines and do not have a medical condition that severely impairs their immune system. For 2026, the study will directly compare the immunogenicity and reactogenicity of the 2026 Novavax recombinant COVID-19 vaccine with the 2026 Pfizer/BioNTech mRNA COVID-19 vaccine.

Being tested
Pfizer-BioNTech mRNA COVID-19 vaccine, Novavax recombinant protein vaccine
Keywords
COVID-19 vaccine, Influenza vaccine, Respiratory virus vaccine, Immunogenicity
Medical subject headings
COVID-19, Influenza, Human

What participants receive

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

  • Pfizer-BioNTech mRNA COVID-19 vaccineDrug

    COVID-19 Vaccine, mRNA

  • Novavax recombinant protein vaccineDrug

    Recombinant protein vaccine

Study groups in NCT07287137
Study groupRoleWhat they receive
For fall of 2026, Arm 1 of the study will be the Pfizer-BioNTech mRNA COVID-19 vacActive comparatorArm 1 of the study will be Pfizer-BioNTech mRNA COVID-19 vaccine
Receives: Drug: Pfizer-BioNTech mRNA COVID-19 vaccine
For fall of 2026, Arm 2 of the study will be the Novavax recombinant protein vaccineActive comparatorArm 2 of the study will be the Novavax recombinant protein vaccine
Receives: Drug: Novavax recombinant protein vaccine

What is being measured

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

  1. Variant-specific immune responses

    The primary endpoint is variant-specific immune response (magnitude and breadth) to licensed recombinant and mRNA COVID-19 products administered to adult MHS beneficiaries who are eligible for a fall COVID-19 vaccine and who are not severely immunocompromised. This will include quantifying the magnitude of binding and neutralizing antibodies to the vaccine variants and to the dominant variant present 30 days and 150 days post-vaccination. Specifically, we will test neutralizing titers (defined as the inverse serum dilution causing a 50% reduction in relative light units in a pseudovirus neutralization assay) and IgG binding antibody levels (measured in arbitrary units) against the following SARS-CoV-2 variants: XFG (vaccine strain), Wuhan-1 (ancestral strain), plus the dominant circulating variant(s) circulating during the fall of 2026 and winter of 2026-2027.

    Measured: IgG binding antibody levels and neutralizing antibody titers will be assessed on serum samples obtained just prior to vaccination, 30 days (+/- 10 days), and 150 days (+/- 10 days) after vaccination.

Timeline

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

  1. First posted17 Dec 2025
  2. Study start12 Nov 2025
  3. Primary completionSep 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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Enrollment of 50-54 individuals to receive the vaccine (up to 27 per arm) per year.
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07287137
Sponsor's protocol ID
IDCRP-154
Acronym
CIRV2
Status last verified
Apr 2026
First submitted
18 Nov 2025
Last updated
11 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • McLeod C, Dymock M, Flanagan KL, Plebanski M, Marshall H, Estcourt MJ, Tjiam MC, Blyth CC, Subbarao K, Mordant FL, Nicholson S, Faust SN, Wadia U, Thornton RB, Ellis Z, Mckenzie A, Marsh JA, Snelling TL, Richmond P. The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old. J Infect. 2024 Dec;89(6):106286. doi: 10.1016/j.jinf.2024.106286. Epub 2024 Sep 26.

    PubMed 39341401

  • National Center for Advancing Translational Sciences. Serious adverse events. Available at ht tps://toolkit.ncats.nih.gov/glossary/serious-adverse-event/; accessed 2 January 2025.

  • Wang W, Lusvarghi S, Subramanian R, Epsi NJ, Wang R, Goguet E, Fries AC, Echegaray F, Vassell R, Coggins SA, Richard SA, Lindholm DA, Mende K, Ewers EC, Larson DT, Colombo RE, Colombo CJ, Joseph JO, Rozman JS, Smith A, Lalani T, Berjohn CM, Maves RC, Jones MU, Mody R, Huprikar N, Livezey J, Saunders D, Hollis-Perry M, Wang G, Ganesan A, Simons MP, Broder CC, Tribble DR, Laing ED, Agan BK, Burgess TH, Mitre E, Pollett SD, Katzelnick LC, Weiss CD. Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history. Cell Host Microbe. 2022 Dec 14;30(12):1745-1758.e7. doi: 10.1016/j.chom.2022.10.012. Epub 2022 Oct 21.

    PubMed 36356586

  • Wang W, Bhushan G, Paz S, Stauft CB, Selvaraj P, Goguet E, Bishop-Lilly KA, Subramanian R, Vassell R, Lusvarghi S, Cong Y, Agan B, Richard SA, Epsi NJ, Fries A, Fung CK, Conte MA, Holbrook MR, Wang TT, Burgess TH, Pollett SD, Mitre E, Katzelnick LC, Weiss CD. Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1. J Virol. 2024 Nov 19;98(11):e0094824. doi: 10.1128/jvi.00948-24. Epub 2024 Oct 4.

    PubMed 39365051

  • Conner TL, Goguet E, Haines-Hull H, et al: Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses. MedRxiv 2024; doi .org/10.1101/2024.05.22.24307751.

  • Laing ED, Weiss CD, Samuels EC, Coggins SA, Wang W, Wang R, Vassell R, Sterling SL, Tso MS, Conner T, Goguet E, Moser M, Jackson-Thompson BM, Illinik L, Davies J, Ortega O, Parmelee E, Hollis-Perry M, Maiolatesi SE, Wang G, Ramsey KF, Reyes AE, Alcorta Y, Wong MA, Lindrose AR, Duplessis CA, Tribble DR, Malloy AMW, Burgess TH, Pollett SD, Olsen CH, Broder CC, Mitre E. Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers. Emerg Infect Dis. 2022 Apr;28(4):828-832. doi: 10.3201/eid2804.212037. Epub 2022 Feb 24.

    PubMed 35203111

  • Jackson-Thompson BM, Goguet E, Laing ED, Olsen CH, Pollett S, Hollis-Perry KM, Maiolatesi SE, Illinik L, Ramsey KF, Reyes AE, Alcorta Y, Wong MA, Davies J, Ortega O, Parmelee E, Lindrose AR, Moser M, Graydon E, Letizia AG, Duplessis CA, Ganesan A, Pratt KP, Malloy AM, Scott DW, Anderson SK, Snow AL, Dalgard CL, Powers JH 3rd, Tribble D, Burgess TH, Broder CC, Mitre E. Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study: an observational cohort study of SARS-CoV-2 infection and vaccination in healthcare workers. BMC Infect Dis. 2021 Jun 9;21(1):544. doi: 10.1186/s12879-021-06233-1.

    PubMed 34107889

  • U.S. Food and Drug Administration. Highlights of prescribing information: COMIRNATY® (COVID-19 Vaccine, mRNA) suspension for injection, for intramuscular use. 2024. Available at ht tps://www.fda.gov/media/151707/download; accessed 2 January 2025.

  • U.S. Food and Drug Administration. Fact Sheet for healthcare providers administering vaccine: Emergency Use Authorization of Novavax COVID-19 Vaccine, adjuvanted (2024 - 2025 formula), for individuals 12 years of age and older. 2024. Available at https://www.fda.gov /media/159897/download; accessed 2 January 2025.

  • Fong Y, Huang Y, Benkeser D, Carpp LN, Anez G, Woo W, McGarry A, Dunkle LM, Cho I, Houchens CR, Martins K, Jayashankar L, Castellino F, Petropoulos CJ, Leith A, Haugaard D, Webb B, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Randhawa AK, Andrasik MP, Kublin JG, Hutter J, Keshtkar-Jahromi M, Beresnev TH, Corey L, Neuzil KM, Follmann D, Ake JA, Gay CL, Kotloff KL, Koup RA, Donis RO, Gilbert PB; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/2019nCoV-301 Principal Investigators and Study Team; United States Government (USG)/CoVPN Biostatistics Team. Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial. Nat Commun. 2023 Jan 19;14(1):331. doi: 10.1038/s41467-022-35768-3.

    PubMed 36658109

  • Weitzman ER, Sherman AC, Levy O. SARS-CoV-2 mRNA Vaccine Attitudes as Expressed in U.S. FDA Public Commentary: Need for a Public-Private Partnership in a Learning Immunization System. Front Public Health. 2021 Jul 16;9:695807. doi: 10.3389/fpubh.2021.695807. eCollection 2021.

    PubMed 34336774

  • Biggs AT, Littlejohn LF. Describing mRNA Vaccine Technology for a Military Audience. Mil Med. 2023 Mar 20;188(3-4):547-554. doi: 10.1093/milmed/usac129.

    PubMed 35584186

  • Marchese AM, Rousculp M, Macbeth J, Beyhaghi H, Seet BT, Toback S. The Novavax Heterologous Coronavirus Disease 2019 Booster Demonstrates Lower Reactogenicity Than Messenger RNA: A Targeted Review. J Infect Dis. 2024 Aug 16;230(2):e496-e502. doi: 10.1093/infdis/jiad519.

    PubMed 37992183

  • Scher AI, Berjohn CM, Byrne C, Colombo RE, Colombo CJ, Edwards MS, Ewers EC, Ganesan A, Jones M, Larson DT, Libraty D, Lindholm DA, Madar CS, Maldonado CJ, Maves RC, Mende K, Richard SA, Rozman JS, Rusiecki J, Smith A, Simons M, Tribble D, Agan B, Burgess TH, Pollett SD; EPICC COVID-19 Cohort Study Group. An Analysis of SARS-CoV-2 Vaccine Reactogenicity: Variation by Type, Dose, and History, Severity, and Recency of Prior SARS-CoV-2 Infection. Open Forum Infect Dis. 2022 Jun 28;9(7):ofac314. doi: 10.1093/ofid/ofac314. eCollection 2022 Jul.

    PubMed 35899278

  • U.S. Food and Drug Administration. FDA Briefing Document. Vaccines and Related Biological Products Advisory Committee Meeting June 5, 2024. 2024. Available at https://www.fda.gov /media/179003/download; accessed 10 October 2024.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Pfizer-BioNTech mRNA COVID-19 vaccine and Novavax recombinant protein vaccine in people with COVID -19 and COVID - 19, run by Henry M. Jackson Foundation for the Advancement of Military Medicine 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 31 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 11 Sep 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Variant-specific immune responses (time frame: IgG binding antibody levels and neutralizing antibody titers will be assessed on serum samples obtained just prior to vaccination, 30 days (+/- 10 days), and 150 days (+/- 10 days) after 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 NCT07287137, which also lists 32 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 11 Sep 2026.

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