Journal Article

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

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

2020

Overview

•BK-SE36/CpG is a candidate blood-stage malaria vaccine against P. falciparum.•In healthy Japanese adults, BK-SE36/CpG has an acceptable safety profile.•No indication of autoimmune condition was observed in BK-SE36/CpG vaccinees.•Two dosing, 21-days apart, of full-dose BK-SE36/CpG was highly immunogenic. 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. 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. 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. 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: adjuvants / Adult / Adults / Africa, Western / Allergy and Immunology / Aluminum / Antibodies / Antibody response / Antigens / Antigens, Protozoan / Autoimmune diseases / BK-SE36 / BK-SE36/CpG / Blood / Clinical trials / Confidence intervals / CpG islands / CpG-ODN(K3) / Double-Blind Method / Epitopes / Follow-Up Studies / Good Manufacturing Practice / Hepatitis B / hospitals / Humans / Immunogenicity / Immunoglobulin G / Immunoglobulin M / Infections / Japan / Kinases / Malaria / Malaria blood-stage vaccine / malaria vaccines / Malaria Vaccines - adverse effects / Malaria, Falciparum - prevention & control / Male / males / oligodeoxyribonucleotides / Oligonucleotides / Parasites / Plasmodium falciparum / Proteins / Safety / SERA5 / Single-Blind Method / Standard deviation / t-test / Vaccination / Vaccines / Vector-borne diseases