Browsing by Author "Yagi, Masanori."

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    PublicationOpen Access
    Antibody titres and boosting after natural malaria infection in BK-SE36 vaccine responders during a follow-up study in Uganda
    (Scientific Reports, 2016-10-05) Yagi, Masanori.; Palacpac, Nirianne M. Q.; Ito, Kazuya.; Oishi, Yuko.; Itagaki, Sawako.; Balikagala, Betty.; Ntege, Edward H.; Yeka, Adoke.; Kanoi, Bernard N.; Katuro, Osbert.
    The malaria vaccine BK-SE36 is a recombinant protein (SE36) based on the Honduras 1 serine repeat antigen-5 of Plasmodium falciparum, adsorbed to aluminium hydroxide gel. The phase Ib trial in Uganda demonstrated the safety and immunogenicity of BK-SE36. Ancillary analysis in the follow-up study of 6–20 year-old volunteers suggest significant differences in time to first episodes of clinical malaria in vaccinees compared to placebo/control group. Here, we aimed to get further insights into the association of anti-SE36 antibody titres and natural P. falciparum infection. Children who received BK-SE36 and whose antibody titres against SE36 increased by ≥1.92-fold after vaccination were categorised as responders. Most responders did not have or only had a single episode of natural P. falciparum infection. Notably, responders who did not experience infection had relatively high anti-SE36 antibody titres post-second vaccination compared to those who were infected. The anti-SE36 antibody titres of the responders who experienced malaria were boosted after infection and they had lower risk of reinfection. These findings show that anti-SE36 antibody titres induced by BK-SE36 vaccination offered protection against malaria. The vaccine is now being evaluated in a phase Ib trial in children less than 5 years old.
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    PublicationOpen Access
    Phase 1b Randomized Trial and Follow-Up Study in Uganda of the Blood-Stage Malaria Vaccine Candidate BK-SE36
    (PLOS ONE, 2013-05-28) Palacpac, Nirianne Marie Q.; Ntege , Edward.; Yeka, Adoke.; Balikagala, Betty.; Suzuki, Nahoko.; Shirai, Hiroki.; Yagi, Masanori.; Ito, Kazuya.; Fukushima, Wakaba.; Hirota, Yoshio.
    Background Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. Methods We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21–40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6–20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130–365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Results Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56–2.43], p = 0.004) and 6–10 year-olds (5.71-fold [95% CI, 2.38–13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24–1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0.24–0.98; p = 0.04). Conclusion BK-SE36 is safe and immunogenic. The promising potential of BK-SE36, observed in the follow-up study, warrants a double-blind phase 1/2b trial in children under 5 years.
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    PublicationOpen Access
    The development of the BK-SE36 malaria vaccine candidate
    (Malaria Journal, 2014-09-22) Palacpac, Nirianne MQ.; Yagi, Masanori.; Ntege, Edward.; Balikagala, Betty.; Yeka, Adoke.; Shirai, Hiroki.; Suzuki, Nahoko.; Okada, Takuya.; Kanoi, Bernard.; Nobuko, Arisue.
    Complex and widespread with about 90% of the global burden in sub-Saharan Africa, malaria remains a significant health problem. Malaria vaccines have the chance to make significant inroads, with RTS,S vaccine candidate as the most advanced candidate. However, the need for a highly efficacious, long-lasting vaccine is still unmet. Continued support for a repertoire of tools for Plasmodium falciparum is needed. A blood-stage vaccine is desirable to deal with morbidity and mortality secondary to P. falciparum infection, and thus would be a valuable strategy in the fight against malaria. The P. falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate. The processing of SERA5 is believed to mediate parasite egress from the infected red blood cell. Field studies show good correlations of anti-SERA antibodies to malaria protection against blood parasitemia, malaria symptoms and severe disease. A Phase 1a trial demonstrated its safety and immunogenicity in malaria naïve Japanese adults. A Phase 1b trial was conducted in the malaria endemic area of Northern Uganda to assess the vaccine’s safety and immunogenicity. BK-SE36 had an acceptable safety and immunogenicity profile. Post-trial, Stage 2 subjects were age-matched to 50 control individuals to compare malaria episodes 130–365 days post-second vaccination. Log-rank test reveal significant differences in BK-SE36 vaccinees vs control group in time-to-first episodes with parasitemias ≥5,000/μL and those with ≥5,000/μL + fever (protective efficacy for the latter is 72%, P < 0.01). BK-SE36 vaccinees have fewer multiple malaria episodes with high parasitemia. We also observed that the antibody titers against SE36 were boosted after episodes of natural infection. Above results show that BK-SE36 could provide some protection against natural P. falciparum infection until 1 year post-second vaccination.