Dataset Information

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

ABSTRACT:

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.

Trial registration

Controlled-Trials.com ISRCTN71619711.

SUBMITTER: Palacpac NM

PROVIDER: S-EPMC3665850 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

Palacpac Nirianne Marie Q NM Ntege Edward E Yeka Adoke A Balikagala Betty B Suzuki Nahoko N Shirai Hiroki H Yagi Masanori M Ito Kazuya K Fukushima Wakaba W Hirota Yoshio Y Nsereko Christopher C Okada Takuya T Kanoi Bernard N BN Tetsutani Kohhei K Arisue Nobuko N Itagaki Sawako S Tougan Takahiro T Ishii Ken J KJ Ueda Shigeharu S Egwang Thomas G TG Horii Toshihiro T

PloS one 20130528 5

<h4>Background</h4>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.<h4>Methods</h4>We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Control ...[more]

PMID: 23724021

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Dataset Information

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

Background

Methods

Results

Conclusion

Trial registration

Publications

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

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