First-in-human randomised trial and follow-up study of Plasmodium falciparum blood-stage malaria vaccine BK-SE36 with CpG-ODN(K3)
| Autor: | Tomomi Yamada, Kiyoshi Okada, Takahiro Tougan, Sumiyuki Nishida, Jyotheeswara R. Edula, Yuko Oishi, Kouji Yamamoto, Toshihiro Horii, Kohhei Tetsutani, Akira Myoui, Ken Ishii, Masanori Yagi, Sachiko Ezoe, Nirianne Marie Q. Palacpac, Masaki Taira, Haruhiko Hirata, Atsushi Ogata |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty CpG Oligodeoxynucleotide Plasmodium falciparum 030231 tropical medicine Antigens Protozoan 03 medical and health sciences 0302 clinical medicine Double-Blind Method Japan Internal medicine Malaria Vaccines medicine Humans Single-Blind Method 030212 general & internal medicine Malaria Falciparum General Veterinary General Immunology and Microbiology biology Malaria vaccine business.industry Immunogenicity Public Health Environmental and Occupational Health medicine.disease biology.organism_classification Clinical trial Vaccination Africa Western Infectious Diseases CpG site Molecular Medicine business Malaria Follow-Up Studies |
| Zdroj: | Vaccine. 38:7246-7257 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2020.09.056 |
| Popis: | 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 naive 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 naive 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. |
| Databáze: | OpenAIRE |
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