Abstract
BackgroundIdentification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development. Among functional assays, the neutrophil antibody-dependent respiratory burst (ADRB) induced by opsonized Plasmodium falciparum merozoites has been correlated with acquired immunity to clinical malaria in endemic areas, but the target merozoite antigens are unknown. Here, the contribution of antibodies to the conserved C-terminal domain of the P. falciparum merozoite surface protein-1 (PfMSP1p19) in mediating ADRB was investigated in sera from individuals living in two Senegalese villages with differing malaria endemicity.MethodsAnti-PfMSP1p19 antibody levels in sera from 233 villagers were investigated and the involvement of anti-PfMSP1p19 antibodies in ADRB was explored in a subset of samples using (1) isogenic P. falciparum parasite clones expressing P. falciparum or Plasmodium chabaudi MSP1p19; (2) PfMSP1p19-coated plaque ADRB; and, (3) ADRB triggering using sera depleted from PfMSP1p19 antibodies by absorption onto the baculovirus recombinant antigen.ResultsADRB activity correlated with anti-PfMSP1p19 IgG levels (P < 10−3). A substantial contribution of PfMSP1p19 antibody responses to ADRB was confirmed (P < 10−4) in an age-adjusted linear regression model. PfMSP1p19 antibodies accounted for 33.1 % (range 7–54 %) and 33.2 % (range 0–70 %) of ADRB activity evaluated using isogenic merozoites (P < 10−3) and depleted sera (P = 0.0017), respectively. Coating of PfMSP1p19 on plates induced strong ADRB in anti-PfMSP1p19-positive sera.ConclusionThese data show that naturally acquired P. falciparum MSP1p19 antibodies are potent inducers of neutrophil ADRB and support the development of PfMSP1p19-based malaria vaccine using ADRB assay as a functional surrogate for protection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0935-5) contains supplementary material, which is available to authorized users.
Highlights
Identification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development
Prevalence and levels of PfMSP1p19‐binding IgG and their relationship with antibody‐dependent respiratory burst activity in individual sera The prevalence and levels of IgG specific for PfMSP1p19 were first determined in a set of 233 endemic sera, including 119 from Dielmo and 114 from Ndiop
Prevalence of IgG to PfMSP1p19 was high, with 74 and 86 % of responders in the Dielmo and Ndiop cohorts, respectively. Both seropositivity and IgG levels to PfMSP1p19 were higher in Dielmo than Ndiop (P = 0.023 and P = 0.009 by Fisher’s exact test and Mann Withney rank sum test, respectively)
Summary
Identification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development. The neutrophil antibody-dependent respiratory burst (ADRB) induced by opsonized Plasmodium falciparum merozoites has been correlated with acquired immunity to clinical malaria in endemic areas, but the target merozoite antigens are unknown. Antibody-dependent cellular inhibition (ADCI), whereby monocytes activated by antibodycoated merozoites inhibit development of intracellular erythocytic stages has been associated with protection in humans [14]. The respiratory burst activity of human polymorphonuclear neutrophils (PMN) triggered by P. falciparum merozoites and immune IgG from individuals living in endemic areas has been previously characterized and quantified [19]. The antibody-dependent respiratory burst (ADRB) activity significantly correlated with acquired clinical protection, suggesting that the release of extracellular oxygen radicals by activated PMNs may represent a key effector mechanism of naturally acquired immunity to malaria [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
