First-in-human randomised trial and follow-up study of Plasmodium falciparum blood-stage malaria vaccine BK-SE36 with CpG-ODN(K3).

Atsushi Ogata, Toshihiro Horii, Akira Myoui, Ken J Ishii, Takahiro Tougan, Yuko Oishi, Jyotheeswara R Edula, Masanori Yagi, Tomomi Yamada, Sachiko Ezoe, Haruhiko Hirata, Sumiyuki Nishida, Masaki Taira, Kiyoshi Okada, Kouji Yamamoto, Kohhei Tetsutani, Nirianne Marie Q Palacpac

Journal: Vaccine 2021;38(46):7246-7257

PMID: 33012605

Full Text on Elsevier Science View on PubMed

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 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.

Address: 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.; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.; 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.; Data Coordinating Center, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.; Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.; 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.; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.; Medical Center for Translational Research, Department of Medical Innovation, Osaka University Hospital, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: [email protected].; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: [email protected].

DOI: 10.1016/j.vaccine.2020.09.056

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MeSH Terms: Adult, Africa, Western, Antigens, Protozoan, Double-Blind Method, Follow-Up Studies, Humans, Japan, Malaria Vaccines, Malaria, Falciparum, Male, Plasmodium falciparum, Single-Blind Method