Journal article
A phase I study of the safety, Reactogenicity and immunogenicity of two Quadrivalent seasonal influenza vaccines (Fluzone® or Flublok®) with or without one of two adjuvants (AF03 or Advax-CpG55.2) in healthy adults 18–45 years of age
Vaccine, Vol.54, 126991
04/30/2025
DOI: 10.1016/j.vaccine.2025.126991
PMID: 40107003
Abstract
Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines. This phase I, randomized, double-blind trial evaluated the safety and immunogenicity of one dose of 2018/2019 quadrivalent influenza vaccine (either Fluzone® or Flublok®) administered intramuscularly with or without one of two adjuvants (AF03 or Advax-CpG55.2). A total of 241 healthy adults aged 18–45 years were enrolled and randomized to 1 of 6 groups. Groups 1–3 received one dose of Fluzone® QIV 2018/2019 administered alone or with AF03 or Advax-CpG55.2 and Groups 4–6 received one dose of Flublok® QIV 2018/2019 alone or with one of these two adjuvants. All participants received Fluzone® or Flublok QIV 2019/2020 ninety days later. Primary objectives were to evaluate safety and reactogenicity along with changes in hemagglutinin inhibition (HAI), neuraminidase inhibition (NAI) and neutralizing antibodies to 2018/2019 seasonal influenza antigens, comparing Day 1 and Day 29 titers. Secondary objectives evaluated the impact of adjuvants on immune responses after subsequent doses of unadjuvanted seasonal influenza vaccine and immunologic responses to heterologous influenza H1 and H3 antigens. Overall, the adjuvanted vaccines were safe and generated robust immune responses against both homologous and heterologous strains. Similar responses were seen across all six study arms. Both adjuvants were associated with qualitatively improved immune responses against some strains at varying timepoints, but results were inconsistent. There were no substantial differences in safety or reactogenicity identified between the study groups and all vaccine formulations were well tolerated. In this highly immunologically-experienced cohort, neither AF03 nor Advax-CpG55.2 demonstrated notable benefit when added to the seasonal influenza vaccine. (ClinicalTrials.gov ID# NCT03945825).
•First human study to use the combination of Advax and CpG55.2 as an adjuvant.•Vaccine candidates induced robust antibody responses to multiple influenza strains.•Each of the vaccine candidates were safe and well-tolerated.•High baseline immunity may have overshadowed potential adjuvant effects.•Not adequately powered to identify significant differences between adjuvants.
Details
- Title: Subtitle
- A phase I study of the safety, Reactogenicity and immunogenicity of two Quadrivalent seasonal influenza vaccines (Fluzone® or Flublok®) with or without one of two adjuvants (AF03 or Advax-CpG55.2) in healthy adults 18–45 years of age
- Creators
- Theresa E. Hegmann - University of IowaEmmanuel B. Walter - Duke Medical CenterMichael J. Smith - Duke UniversityJames Campbell - University of Maryland, BaltimoreHana M. El Sahly - Baylor College of MedicineJennifer A. Whitaker - Baylor College of MedicineC. Buddy Creech - Vanderbilt University Medical CenterIrina V. Ustyugova - SanofiAna P. Goncalvez - SanofiAseem Pandey - SanofiTimothy Alefantis - SanofiSaranya Sridhar - SanofiYoshikazu Honda-Okubo - VaxineNikolai Petrovsky - VaxineSharon E. Frey - Saint Louis UniversityGetahun Abate - Saint Louis UniversityGrant Paulsen - Cincinnati Children's Hospital Medical CenterEvan J. Anderson - Emory UniversityChristina A. Rostad - Emory UniversityNadine Rouphael - Emory UniversityMamodikoe Makhene - National Institute of Allergy and Infectious DiseasesPaul C. Roberts - National Institute of Allergy and Infectious DiseasesBonifride Tuyishimire - EmmesChristopher Bryant - EmmesPatricia Winokur - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Vaccine, Vol.54, 126991
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.vaccine.2025.126991
- PMID
- 40107003
- ISSN
- 0264-410X
- eISSN
- 1873-2518
- Grant note
- Division of Microbiology and Infectious Diseases at the National Institutes of Health: HHSN272201300020I, HHSN27 2201300015I, HHSN272201300021I, HHSN272201300016I, HHSN272201300017I, HHSN272201300022I, 75N93021C00012, HHSN272201300023I, HHSN272201300018I Vaxine Pty LtdNational Institute of Allergy and Infectious Diseases of the National Institutes of Health: HHS-N272201400053C, HHSN272201800044C, HHSN272201800024C
This work was supported by Funding provided by the Division of Microbiology and Infectious Diseases at the National Institutes of Health under contracts HHSN272201300020I (University of Iowa) , HHSN27 2201300015I (Baylor College of Medicine) , HHSN272201300021I (Saint Louis University) , HHSN272201300016I (Cincinnati Children's Medical Center) , HHSN272201300017I (Duke University) , HHSN272201300023I (Vanderbilt University Medical Center) , HHSN272201300018I (Emory University) , HHSN272201300022I (University of Maryland School of Medicine Center for Vaccine Development) and 75N93021C00012 (Emmes Corporation) . Development of Advax-CpG55.2 adjuvant was supported by funding from Vaxine Pty Ltd. and National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Contract HHS-N272201400053C, HHSN272201800044C, and HHSN272201800024C.
- Language
- English
- Electronic publication date
- 03/18/2025
- Date published
- 04/30/2025
- Academic Unit
- Physician Assistant Studies; Infectious Diseases; Medicine Administration; Internal Medicine
- Record Identifier
- 9984802013402771
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