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Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3? and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

ABSTRACT: BACKGROUND:Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3? (PvMSP3?) is a target of acquired immunity and a potential vaccine candidate. METHODS:Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3?, were measured by means of enzyme-linked immunosorbent assay. RESULTS:The seroprevalence of complement-fixing antibodies was highest against the PvMSP3? central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3?. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28. CONCLUSION:Our study demonstrates that PvMSP3? antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

SUBMITTER: Oyong DA

PROVIDER: S-EPMC6834073 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3α and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

Oyong Damian A DA Wilson Danny W DW Barber Bridget E BE William Timothy T Jiang Jianlin J Galinski Mary R MR Fowkes Freya J I FJI Grigg Matthew J MJ Beeson James G JG Anstey Nicholas M NM Boyle Michelle J MJ

The Journal of infectious diseases 20191101 12

<h4>Background</h4>Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.<h4>Methods</h4>Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Comp ...[more]

PMID: 31419296

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Project description:BackgroundPlasmodium vivax is the most widely distributed human malaria parasite and accounts for approximately the same number of malaria cases as Plasmodium falciparum in India. Compared with P. falciparum, P. vivax is difficult to eradicate because of its tendency to cause relapses, which impacts treatment and control strategies. The genetic diversity of these parasites, particularly of the merozoite surface protein-3 alpha (msp-3α) gene, can be used to help develop a potential vaccine. The present study aimed to investigate the genetic diversity of P. vivax using the highly polymorphic antigen gene msp-3α and to assess the suitability of using this gene for population genetic studies of P. vivax isolates and was carried out in 2004-06. No recent study has been reported for MSP 3α in the recent decade in India. Limited reports are available on the genetic diversity of the P. vivax population in India; hence, this report aimed to improve the understanding of the molecular epidemiology of the parasite by studying the P. vivax msp-3α (Pvmsp-3α) marker from P. vivax field isolates from India.MethodsField isolates were collected from different sites distributed across eight states in India. A total of 182 blood samples were analysed by a nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using the HhaI and AluI restriction enzymes to determine genetic msp-3α variation among clinical P. vivax isolates.ResultsBased on the length variants of the PCR products of Pvmsp-3α gene, three allele sizes, Type A (1.8 kb), Type B (1.5 kb) and Type C (1.2 kb) were detected among the 182 samples. Type A PCR amplicon was more predominant (75.4 %) in the samples compared with the Type B (14.3 %) and Type C (10.0 %) polymorphisms. Among all of the samples analysed, 8.2 % were mixed infections detected by PCR alone. Restriction fragment length polymorphism (RFLP) analysis involving the restriction enzymes AluI and HhaI generated fragment sizes that were highly polymorphic and revealed substantial diversity at the nucleotide level.ConclusionsThe present study is the first extensive study in India using the Pvmsp-3α marker. The results indicated that Pvmps-3α, a polymorphic genetic marker of P. vivax, exhibited considerable variability in infection prevalence in field isolates from India. Additionally, the mean multiplicity of infection observed at all of the study sites indicated that P. vivax is highly diverse in nature in India, and Pvmsp-3α is likely an effective and promising epidemiological marker.

Project description:BackgroundAlthough a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium vivax merozoite surface antigen 180 (PvMSA180, PVX_094920), a novel P. vivax antigenic protein.MethodsThe target gene was amplified as four overlapping domains (D1, D2, D3 and D4) to enable expression of the recombinant protein using cell-free and bacterial expression systems. The recombinant PvMSA180 proteins were used in protein microarrays to evaluate the humoral immune response of 72 vivax-infected patients and 24 vivax-naïve individuals. Antibodies produced in mice against the PvMSA180-D1 and -D4 domains were used to assess the subcellular localization of schizont-stage parasites with immunofluorescence assays. A total of 51 pvmsa180 sequences from 12 countries (41 sequences from PlasmoDB and 6 generated in this study) were used to determine the genetic diversity and genealogical relationships with DNAsp and NETWORK software packages, respectively.ResultsPvMSA180 consists of 1603 amino acids with a predicted molecular mass of 182 kDa, and has a signal peptide at the amino-terminus. A total of 70.8% of patients (51/72) showed a specific antibody response to at least one of the PvMSA180 domains, and 20.8% (15/72) exhibited a robust antibody response to at least three of the domains. These findings suggest that PvMSA180 is targeted by the humoral immune response during natural infection with P. vivax. Immunofluorescence analysis demonstrated that PvMSA180 is localized on the merozoite surface of schizont-stage parasites, and pvmsa180 sequences originating from various geographic regions worldwide showed low genetic diversity. Twenty-two haplotypes were found, and haplotype 6 (Hap_6, 77%) of pvmsa180 was detected in isolates from six countries.ConclusionsA novel P. vivax surface protein, PvMSA180, was characterized in this study. Most of P. vivax-infected patients had specific antibodies against particular antigenic domains, indicating that this protein is immunogenic in naturally exposed populations. Genetic analysis of worldwide isolates showed that pvmsa180 is less polymorphic than other well-known candidates and that some haplotypes are common to several countries. However, additional studies with a larger sample size are necessary to evaluate the antibody responses in geographically separated populations, and to identify the function of PvMSA180 during parasite invasion.

Project description:BACKGROUND: Malaria caused by Plasmodium vivax is a major public health problem worldwide that affects 70-80 million people in the Middle East, Asia, Western Pacific, South America and the Caribbean. Despite its epidemiological importance, few antigens from this parasite species have been characterized to date compared to Plasmodium falciparum, due in part to the difficulties of maintaining an in vitro culture of P. vivax. This study describes the identification of the P. falciparum thrombospondin-related apical merozoite protein homologue in P. vivax (PvTRAMP) and examines its potential to be further evaluated as vaccine candidate. METHODS: The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of P. vivax. Genes adjacent to pvtramp were identified in silico to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in P. falciparum and Plasmodium knowlesi. The pvtramp gene was amplified from cDNA of P. vivax schizont stages, cloned and expressed in Escherichia coli. Anti-PvTRAMP antisera was obtained by inoculating rabbits with PvTRAMP B cell epitopes produced as synthetic peptides in order to assess its recognition in parasite lysates by Western blot and in intact parasites by indirect immunofluorescence. The recognition of recombinant PvTRAMP by sera from P. vivax-infected individuals living in endemic areas was also assessed by ELISA. RESULTS: The PfTRAMP homologue in P. vivax, here denoted as PvTRAMP, is a 340-amino-acid long antigen encoded by a single exon that could have a potential role in cytoadherence, as indicated by the presence of a thrombospondin structural homology repeat (TSR) domain. According to its transcription and expression profile, PvTRAMP is initially located at the parasite's apical end and later on the parasite surface. Recombinant PvTRAMP is recognized by sera from infected patients, therefore, indicating that it is targeted by the immune system during a natural infection with P. vivax. CONCLUSIONS: The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the Aotus animal model.

Dataset Information

Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3? and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

Publications

Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3α and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

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