Safety and immunogenicity of a quadrivalent seasonal influenza vaccine adjuvanted with hydroxypropyl-β-cyclodextrin: A phase 1 clinical trial.

Akane Watanabe, Sumiyuki Nishida, Temizöz Burcu, Takayuki Shibahara, Takato Kusakabe, Etsushi Kuroda, Ken J Ishii, Atsushi Kumanogoh

Journal: Vaccine 2022;40(31):4150-4159

PMID: 35672178

Free Full Text on Elsevier Science View on PubMed

Abstract

OBJECTIVES

Hydroxypropyl-β-cyclodextrin (HP-β-CyD), an oligosaccharide used as an excipient in pharmaceutical preparation, was recently reported to function as a vaccine adjuvant to co-administered antigens. In this study, we investigated the safety and immunogenicity of a seasonal influenza vaccine adjuvanted with HP-β-CyD (FluCyD-vac) in healthy adults compared with those of a standard seasonal influenza vaccine (Flu-vac).

METHODS

We conducted a single-blinded randomized phase 1 clinical trial study, and used two quadrivalent split seasonal influenza vaccines: FluCyD-vac containing 9 μg of HA/strain and 20% w/v of HP-β-CyD, and Flu-vac containing 15 μg of hemagglutinin (HA)/strain only. All participants were randomly assigned to receive a single dose of Flu/CyD-vac or Flu-vac at a ratio of 2:1. We assessed solicited and unsolicited adverse events (AEs) and immune responses using hemagglutination inhibition (HI) titers. In addition, we assessed T-cell function in peripheral blood mononuclear cells (PBMCs), after stimulation with HA vaccine strains, using flow cytometry.

RESULTS

Among 36 healthy volunteers enrolled in the study (FluCyD-vac, n = 24; Flu-vac, n = 12), FluCyD-vac was well tolerated. Most of the solicited AEs were mild local skin reactions at the injection site. No serious AEs were reported in either group. HI titers 21 days after vaccination with FluCyD-vac were comparable with those of Flu-vac and sufficient to meet international criteria, despite reduced HA antigen doses. When PBMCs were stimulated with the four HA antigens in the vaccine, tumor necrosis factor (TNF)-α-producing CD4 T cells were enhanced in the FluCyD-vac group.

CONCLUSION

FluCyD-vac was well-tolerated and immunogenic, despite containing 40% less HA antigens than Flu-vac. This study showed that HP-β-CyD is a potentially safe, novel adjuvant for human influenza vaccine.

CLINICAL TRIAL REGISTRY

UMIN000028530.

Address: Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan; Laboratory of Thermo-therapeutics for vascular dysfunction, Osaka University, Suita, Osaka, Japan.; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. Electronic address: [email protected].; Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Division of Vaccine Science, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan; Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.; Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.; Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan; Department of Immunopathology, WPI, Immunology Frontier Research Center (iFReC), Osaka University, Suita, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan; Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Osaka, Japan.

DOI: 10.1016/j.vaccine.2022.05.060