Abstract
BackgroundA Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe.The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12–24 months living in malaria endemic area of Burkina Faso.MethodsThe study was a double-blind, randomized, controlled, dose escalation phase Ib trial, designed to assess the safety, reactogenicity and immunogenicity of three doses of either 15 or 30 µg of MSP3-LSP adsorbed on aluminum hydroxide in 45 children 12 to 24 months of age randomized into three equal groups. Each group received 3 vaccine doses (on days 0, 28 and 56) of either 15 µg of MSP3-LSP, 30 µg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were visited at home daily for the 6 days following each vaccination to solicit symptoms which might be related to vaccination. Serious adverse events occurring during the study period (1 year) were recorded. Antibody responses to MSP3-LSP were measured on days 0, 28, 56 and 84.ResultsAll 45 enrolled children received three MSP3 vaccine doses. No serious adverse events were reported. Most of the adverse events reported were mild to moderate in severity. The only reported local symptoms with grade 3 severity were swelling and induration, with an apparently dose related response. All grade 3 adverse events resolved without any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti-MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly the isotypes involved in the monocyte-dependent mechanism of P. falciparum parasite-killing.ConclusionOur results support the promise of MSP3-LSP as a malaria vaccine candidate, both in terms of tolerability and of immunogenicity. Further assessment of the efficacy of this vaccine is recommended.Trial RegistrationClinicalTrials.gov NCT00452088
Highlights
The burden of malaria remains high in sub-Saharan countries despite the extensive deployment of existing control tools, such as insecticide-treated materials, intermittent preventive treatment, and artemisinin-based combination therapy (ACT) [1]
The protection afforded by passive transfer of IgG from African adults into infected Thai children identified the cooperation of IgG with blood monocytes as a main defense mechanism in human beings in an antibody dependent, cellular inhibitory fashion (ADCI)
The monocyte-dependent mechanism implies that only the cytophilic classes of IgG, namely IgG1and IgG3, are important in mediating the effects, and epidemiological studies have confirmed that protection is associated with such cytophilic responses against merozoite surface protein 3 (MSP3) [2,3,4,5]
Summary
The burden of malaria remains high in sub-Saharan countries despite the extensive deployment of existing control tools, such as insecticide-treated materials, intermittent preventive treatment, and artemisinin-based combination therapy (ACT) [1]. The protection afforded by passive transfer of IgG from African adults into infected Thai children identified the cooperation of IgG with blood monocytes as a main defense mechanism in human beings in an antibody dependent, cellular inhibitory fashion (ADCI). The monocyte-dependent mechanism implies that only the cytophilic classes of IgG, namely IgG1and IgG3, are important in mediating the effects, and epidemiological studies have confirmed that protection is associated with such cytophilic responses against MSP3 [2,3,4,5]. A Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe. The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12– 24 months living in malaria endemic area of Burkina Faso
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