Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

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 2025 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine.

Timeline

Start

2025-11-12

Primary completion

2027-09

Completion

2027-09

Publications

• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee June 5, 2024 Meeting Announcement. 2024. Available at https://www.fda.gov /advisory-committees/advisory-committee-calendar/vaccines-and-related-biological- products-advisory-committee-june-5-2024-meeting-announcement; accessed 10 October 2024.
• Background Winkler EL, Stahlman SL, Wells NY, Chauhan AV, Hiban KM, Costello AA, Mancuso JD. COVID-19 Booster Vaccination in the U.S. Military, August 2021-January 2022. Am J Prev Med. 2023 Feb;64(2):270-274. doi: 10.1016/j.amepre.2022.07.017. Epub 2022 Aug 29.
• Background Centers for Disease Control and Prevention. ACIP Evidence to Recommendations (EtR) for Use of 2024-2025 COVID-19 Vaccines in Persons ≥6 Months of Age. 2024. Available at https:// www.cdc.gov/vaccines/acip/recs/grade/covid-19-2024-2025-6-months-and-older-etr. html; accessed 10 October 2024.
• Background Centers for Disease Control and Prevention. Staying Up to Date with COVID-19 Vaccines. 2024. Available at https://www.cdc.gov/covid/vaccines/stay-up-to-date.html; accessed 10 October 2024.
• Background Lam ICH, Zhang R, Man KKC, Wong CKH, Chui CSL, Lai FTT, Li X, Chan EWY, Lau CS, Wong ICK, Wan EYF. Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection. Nat Commun. 2024 Feb 26;15(1):1716. doi: 10.1038/s41467-024-45953-1.
• Background Richard SA, Scher AI, Rusiecki J, Byrne C, Berjohn CM, Fries AC, Lalani T, Smith AG, Mody RM, Ganesan A, Huprikar N, Colombo RE, Colombo CJ, Schofield C, Lindholm DA, Mende K, Morris MJ, Jones MU, Flanagan R, Larson DT, Ewers EC, Bazan SE, Saunders D, Maves RC, Livezey J, Maldonado CJ, Edwards MS, Rozman JS, O'Connell RJ, Simons MP, Tribble DR, Agan BK, Burgess TH, Pollett SD; EPICC COVID-19 Cohort Study Group. Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study. Open Forum Infect Dis. 2023 Nov 17;10(12):ofad579. doi: 10.1093/ofid/ofad579. eCollection 2023 Dec.
• Background Hone E, Pollett SD, Richard SA, et al, editors. The Molecular Epidemiology and Congregate Transmission Dynamics of Acute Respiratory Infections (ARIs) at United States Naval Academy (USNA) during Plebe Summer. Poster #113. Military Health System Research Symposium; 2024; Kissimmee, FL.
• Background Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries Among Active Component Members of the U.S. Armed Forces, 2023. 2024. Available at https://www. health.mil/News/Articles/2024/06/01/MSMR-Health-Care-Burden-Active-Component; accessed 10 October 2024.
• Background Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries Among Non-Service Member Beneficiaries of the Military Health System, 2023. 2024. Available at https: //health.mil/News/Articles/2024/07/01/MSMR-MHS-Beneficiaries-2023; accessed 10 October 2024.
• Background Taylor CA, Patel K, Pham H, Kirley PD, Kawasaki B, Meek J, Witt L, Ryan PA, Reeg L, Como-Sabetti K, Domen A, Anderson B, Bushey S, Sutton M, Talbot HK, Mendez E, Havers FP; COVID-NET Surveillance Team. COVID-19-Associated Hospitalizations Among U.S. Adults Aged >/=18 Years - COVID-NET, 12 States, October 2023-April 2024. MMWR Morb Mortal Wkly Rep. 2024 Oct 3;73(39):869-875. doi: 10.15585/mmwr.mm7339a2.
• Background National Center for Health Statistics. Provisional COVID-19 Mortality Surveillance. Centers for Disease Control and Prevention; 2024. Available at https://www.cdc.gov/nchs/nvss/vsrr /covid19/index.htm; accessed 10 October 2024.
• Background Kasper MR, Geibe JR, Sears CL, Riegodedios AJ, Luse T, Von Thun AM, McGinnis MB, Olson N, Houskamp D, Fenequito R, Burgess TH, Armstrong AW, DeLong G, Hawkins RJ, Gillingham BL. An Outbreak of Covid-19 on an Aircraft Carrier. N Engl J Med. 2020 Dec 17;383(25):2417-2426. doi: 10.1056/NEJMoa2019375. Epub 2020 Nov 11.
• Background Mease LE, Smith AM. Surveillance snapshot: A simple model estimating the impact ofCOVID-19 on lost duty days among U.S. service members. MSMR. 2021 Sep 1;28(9):17. No abstract available.
• Background U.S. Department of Defense. Coronavirus: DoD Response. 2024. Available at https://www. defense.gov/Spotlights/Coronavirus-DOD-Response/; accessed 8 October 2024.
• Background Absolute and relative morbidity burdens attributable to various illnesses and injuries, active component, U.S. Armed Forces, 2020. MSMR. 2021 May;28(5):2-9. No abstract available.
• Background 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.
• Background Gray GC, Callahan JD, Hawksworth AW, Fisher CA, Gaydos JC. Respiratory diseases among U.S. military personnel: countering emerging threats. Emerg Infect Dis. 1999 May-Jun;5(3):379-85. doi: 10.3201/eid0503.990308.

Drugs

Indications