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Clinical Trial
. 2025 Apr 30:54:126991.
doi: 10.1016/j.vaccine.2025.126991. Epub 2025 Mar 18.

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

Theresa E Hegmann  1 , Emmanuel B Walter  2 , Michael J Smith  3 , James Campbell  4 , Hana M El Sahly  5 , Jennifer A Whitaker  6 , C Buddy Creech  7 , Irina V Ustyugova  8 , Ana P Goncalvez  9 , Aseem Pandey  10 , Timothy Alefantis  10 , Saranya Sridhar  11 , Yoshikazu Honda-Okubo  12 , Nikolai Petrovsky  13 , Sharon E Frey  14 , Getahun Abate  15 , Grant Paulsen  16 , Evan J Anderson  17 , Christina A Rostad  18 , Nadine Rouphael  19 , Mamodikoe Makhene  20 , Paul C Roberts  21 , Bonifride Tuyishimire  22 , Christopher Bryant  23 , Patricia Winokur  24
Affiliations
Clinical Trial

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

Theresa E Hegmann et al. Vaccine. .

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).

Keywords: AF03; Adjuvant; Advax-CpG55.2; Immunogenicity; Neuraminidase; Quadrivalent influenza vaccine.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emmanuel B. Walter reports a relationship with Pfizer Inc. that includes: consulting or advisory and funding grants. Emmanuel B. Walter reports a relationship with Moderna Inc. that includes: funding grants. Emmanuel B. Walter reports a relationship with Seqirus USA Inc. that includes: funding grants. Emmanuel B. Walter reports a relationship with Clinetic that includes: funding grants. Emmanuel B. Walter reports a relationship with Najit Technologies Inc. that includes: funding grants. Emmanuel B. Walter reports a relationship with Vaxcyte Inc. that includes: consulting or advisory. Emmanuel B. Walter reports a relationship with ILiAD Biotechnologies LLC that includes: consulting or advisory. Emmanuel B. Walter served on a Data Safety Monitoring Board for Shionogi. Michael Smith reports a relationship with Pfizer that includes: funding grants. Michael Smith reports a relationship with Sanofi Pasteur Inc. that includes: funding grants. C. Buddy Creech reports a relationship with Sanofi Pasteur Inc. that includes: consulting or advisory. C. Buddy Creech reports a relationship with Moderna Inc. that includes: consulting or advisory. C. Buddy Creech reports a relationship with GlaxoSmithKline Inc. that includes: consulting or advisory. Irina V. Ustyugova reports financial support, administrative support, and equipment, drugs, or supplies were provided by Sanofi Vaccines. Irina V. Ustyugova reports a relationship with Sanofi Vaccines that includes: employment and equity or stocks. Ana P. Goncalvez reports financial support, administrative support, and equipment, drugs, or supplies were provided by Sanofi Vaccines. Ana P. Goncalvez reports a relationship with Sanofi Vaccines that includes: employment and equity or stocks. Aseem Pandey reports financial support, administrative support, and equipment, drugs, or supplies were provided by Sanofi Vaccines. Aseem Pandey reports a relationship with Sanofi Vaccines that includes: employment and equity or stocks. Timothy Alefantis reports financial support, administrative support, and equipment, drugs, or supplies were provided by Sanofi. Timothy Alefantis reports a relationship with Sanofi Pasteur that includes: employment and equity or stocks. Timothy Alefantis reports a relationship with Icosavax, Inc. that includes: employment and equity or stocks. Timothy Alefantis is formerly an employee of Sanofi Pasteur and Icosavax. Saranya Sridhar reports a relationship with Sanofi that includes: equity or stocks. Saranya Sridhar has patent pending to Sanofi. Yoshikazu Honda-Okubo reports financial support was provided by Vaxine Pty Ltd. Yoshikazu Honda-Okubo reports a relationship with Vaxine Pty Ltd. that includes: employment. Yoshikazu Honda-Okubo has patent #P2014–515234 issued to Vaxine Pty Ltd. Nikolai Petrovsky reports equipment, drugs, or supplies was provided by Vaxine Pty Ltd. Nikolai Petrovsky reports a relationship with Vaxine Pty Ltd. that includes: board membership and employment. Nikolai Petrovsky has patent on a vaccine adjuvant composition comprising inulin particles issued to Vaxine Pty Ltd. Evan Anderson reports a relationship with Moderna Inc. that includes: employment and equity or stocks. Evan Anderson is currently employed by Moderna. Christina Rostad reports financial support was provided by Pfizer Inc. Christina Rostad reports financial support was provided by Moderna Inc. Christina Rostad reports financial support was provided by Merck & Co Inc. Christina Rostad reports financial support was provided by Sanofi. Christina Rostad reports financial support was provided by Janssen Pharmaceuticals Inc. Christina Rostad has patents on Chimeric RSV, Immunogenic Compositions, and Methods of Use with royalties paid to Meissa Vaccines, Inc. Christina Rostad has patents on RSV Live-Attenuated Vaccine Candidates with Deleted G-Protein Mucin Domains issued to Emory University. Nadine Rouphael reports a relationship with Emory University School of Medicine that includes: employment. Emory receives funds for NR to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company and Pfizer. NR served on selected advisory boards for Sanofi, Seqirus, Pfizer and Moderna and is a paid clinical trials safety consultant for ICON, CyanVac, Imunon and EMMES. Bonifride Tuyishimire reports financial support was provided by The Emmes Company LLC. Christopher Bryant reports financial support was provided by The Emmes Company LLC. Patricia Winokur reports a relationship with Emmes Corporation that includes: board membership. Patricia Winokur reports a relationship with Blue Lake Biotechnology that includes: board membership. Dr. Winokur has received research funding from Pfizer. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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