Sachiko Ezoe1, Nirianne Marie Q Palacpac2, Kohhei Tetsutani3, Kouji Yamamoto4, Kiyoshi Okada5, Masaki Taira6, Sumiyuki Nishida7, Haruhiko Hirata7, Atsushi Ogata7, Tomomi Yamada4, Masanori Yagi2, Jyotheeswara R Edula2, Yuko Oishi2, Takahiro Tougan2, Ken J Ishii3, Akira Myoui8, Toshihiro Horii9. 1. Medical Center for Translational Research, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Environmental Space Infection Control, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 2. Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 3. Laboratory of Adjuvant Innovation/Mockup Vaccine, Center for Vaccine Adjuvant Research, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki City, Osaka 567-0085, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 4. Data Coordinating Center, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 5. Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 6. Medical Center for Translational Research, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 7. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 8. Medical Center for Translational Research, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: myoi@hp-mctr.med.osaka-u.ac.jp. 9. Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: horii@biken.osaka-u.ac.jp.
Abstract
BACKGROUND: BK-SE36 is blood-stage malaria vaccine candidate that is undergoing clinical trials. Here, the safety and immunogenicity of BK-SE36 with a novel adjuvant, CpG-ODN(K3) (thus, BK-SE36/CpG) was assessed in a phase 1a trial in Japan. METHODS: An investigator-initiated, randomised, single-blind, placebo-controlled, dose-escalation study was conducted at Osaka University Hospital with 26 healthy malaria naïve Japanese male adults. The trial was conducted in two stages: Stage/Group 1, half-dose (n = 7 for BK-SE36/CpG and n = 3 for control) and Stage/Group 2, full-dose (n = 11 for BK-SE36/CpG and n = 5 for control). There were two intramuscular vaccinations 21 days apart for both half-dose (0.5 ml: 50 µg SE36 + 500 µg aluminum + 500 µg K3) and full-dose (1.0 ml: 100 µgSE36 + 1000 µg aluminum + 1000 µg K3). A one-year follow-up was done to monitor changes in autoimmune markers and vaccine-induced antibody response. RESULTS:BK-SE36/CpG was well tolerated. Vaccination site reactions were similar to those observed with BK-SE36. During the trial and follow-up period, no subject had clinical evidence of autoimmune disease. The full-dose group had significantly higher titres than the half-dose group (Student's t-test, p = 0.002) at 21 days post-second vaccination. Antibody titres remained above baseline values during 12 months of follow-up. The vaccine induced antibody was mostly composed of IgG1 and IgM, and recognised epitopes close to the polyserine region located in the middle of SE36. CONCLUSIONS:BK-SE36/CpG has an acceptable safety profile. Use of CpG-ODN(K3) greatly enhanced immunogenicity in malaria naïve Japanese adults when compared to BK-SE36 alone. The utility of BK-SE36/CpG is currently under evaluation in a malaria endemic setting in West Africa. TRIAL REGISTRATION: JMACCT Clinical Trial Registry JMA-IIA00109.
RCT Entities:
BACKGROUND:BK-SE36 is blood-stage malaria vaccine candidate that is undergoing clinical trials. Here, the safety and immunogenicity of BK-SE36 with a novel adjuvant, CpG-ODN(K3) (thus, BK-SE36/CpG) was assessed in a phase 1a trial in Japan. METHODS: An investigator-initiated, randomised, single-blind, placebo-controlled, dose-escalation study was conducted at Osaka University Hospital with 26 healthy malaria naïve Japanese male adults. The trial was conducted in two stages: Stage/Group 1, half-dose (n = 7 for BK-SE36/CpG and n = 3 for control) and Stage/Group 2, full-dose (n = 11 for BK-SE36/CpG and n = 5 for control). There were two intramuscular vaccinations 21 days apart for both half-dose (0.5 ml: 50 µg SE36 + 500 µg aluminum + 500 µg K3) and full-dose (1.0 ml: 100 µg SE36 + 1000 µg aluminum + 1000 µg K3). A one-year follow-up was done to monitor changes in autoimmune markers and vaccine-induced antibody response. RESULTS:BK-SE36/CpG was well tolerated. Vaccination site reactions were similar to those observed with BK-SE36. During the trial and follow-up period, no subject had clinical evidence of autoimmune disease. The full-dose group had significantly higher titres than the half-dose group (Student's t-test, p = 0.002) at 21 days post-second vaccination. Antibody titres remained above baseline values during 12 months of follow-up. The vaccine induced antibody was mostly composed of IgG1 and IgM, and recognised epitopes close to the polyserine region located in the middle of SE36. CONCLUSIONS:BK-SE36/CpG has an acceptable safety profile. Use of CpG-ODN(K3) greatly enhanced immunogenicity in malaria naïve Japanese adults when compared to BK-SE36 alone. The utility of BK-SE36/CpG is currently under evaluation in a malaria endemic setting in West Africa. TRIAL REGISTRATION: JMACCT Clinical Trial Registry JMA-IIA00109.
Authors: Edith Christiane Bougouma; Nirianne Marie Q Palacpac; Alfred B Tiono; Issa Nebie; Alphonse Ouédraogo; Sophie Houard; Masanori Yagi; Sam Aboubacar Coulibaly; Amidou Diarra; Takahiro Tougan; Amidou Z Ouedraogo; Issiaka Soulama; Nobuko Arisue; Jean Baptiste Yaro; Flavia D'Alessio; Odile Leroy; Simon Cousens; Toshihiro Horii; Sodiomon B Sirima Journal: Front Immunol Date: 2022-08-31 Impact factor: 8.786