PMID- 35672178
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20220824
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 40
IP  - 31
DP  - 2022 Jul 29
TI  - Safety and immunogenicity of a quadrivalent seasonal influenza vaccine adjuvanted 
      with hydroxypropyl-beta-cyclodextrin: A phase 1 clinical trial.
PG  - 4150-4159
LID - S0264-410X(22)00677-6 [pii]
LID - 10.1016/j.vaccine.2022.05.060 [doi]
AB  - OBJECTIVES: Hydroxypropyl-beta-cyclodextrin (HP-beta-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-beta-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 mug of HA/strain and 20% w/v of 
      HP-beta-CyD, and Flu-vac containing 15 mug 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)-alpha-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-beta-CyD is a potentially safe, novel adjuvant for human influenza 
      vaccine. CLINICAL TRIAL REGISTRY: UMIN000028530.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Watanabe, Akane
AU  - Watanabe A
AD  - 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.
FAU - Nishida, Sumiyuki
AU  - Nishida S
AD  - Department of Respiratory Medicine and Clinical Immunology, Graduate School of 
      Medicine, Osaka University, Suita, Japan. Electronic address: 
      sumiyuki-n@imed3.med.osaka-u.ac.jp.
FAU - Burcu, Temizoz
AU  - Burcu T
AD  - 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.
FAU - Shibahara, Takayuki
AU  - Shibahara T
AD  - 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.
FAU - Kusakabe, Takato
AU  - Kusakabe T
AD  - Center for Vaccine and Adjuvant Research, National Institutes of Biomedical 
      Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
FAU - Kuroda, Etsushi
AU  - Kuroda E
AD  - Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
FAU - Ishii, Ken J
AU  - Ishii KJ
AD  - 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.
FAU - Kumanogoh, Atsushi
AU  - Kumanogoh A
AD  - 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.
LA  - eng
SI  - UMIN-CTR/UMIN000028530
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220604
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Influenza Vaccines)
RN  - 0 (Vaccines, Combined)
RN  - 1I96OHX6EK (2-Hydroxypropyl-beta-cyclodextrin)
SB  - IM
MH  - 2-Hydroxypropyl-beta-cyclodextrin
MH  - Adjuvants, Immunologic
MH  - Adult
MH  - Antibodies, Viral
MH  - Hemagglutination Inhibition Tests
MH  - Humans
MH  - Immunogenicity, Vaccine
MH  - *Influenza Vaccines
MH  - *Influenza, Human/prevention & control
MH  - Leukocytes, Mononuclear
MH  - Seasons
MH  - Vaccines, Combined
OTO - NOTNLM
OT  - Adjuvant
OT  - Cellular immune response
OT  - Hydroxypropyl-beta-cyclodextrin
OT  - Influenza
OT  - Influenza vaccine
OT  - Tumor necrosis factor-alpha
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: The Department of Respiratory Medicine and Clinical Immunology, 
      Graduate School of Medicine, Osaka University, where Atsushi Kumanogoh is a 
      professor, received grants from Daiichi Sankyo Co., Ltd. The Department of 
      Immunology, Hyogo College of Medicine, where Etsushi Kuroda is a professor, 
      received research funding from Daiichi Sankyo Co., Ltd. for a clinical trial 
      independent of this study. The remaining authors have no conflict to declare.
EDAT- 2022/06/08 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/06/07 22:03
PHST- 2021/10/02 00:00 [received]
PHST- 2022/05/16 00:00 [revised]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2022/06/08 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/06/07 22:03 [entrez]
AID - S0264-410X(22)00677-6 [pii]
AID - 10.1016/j.vaccine.2022.05.060 [doi]
PST - ppublish
SO  - Vaccine. 2022 Jul 29;40(31):4150-4159. doi: 10.1016/j.vaccine.2022.05.060. Epub 
      2022 Jun 4.