Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax

Zeyrek, Fadile Yıldız; Palacpac, Nirianne; Yüksel, Fehmi; Yagi, Mamiko; Honjo, Kaori; Fujita, Yukiko; Arisue, Nobuko; Takeo, Satoru; Tanabe, Kazuyuki; Horii, Toshihiro; Tsuboi, Takafumi; Ishii, Ken J.; Coban, Cevayir

doi:10.1371/journal.pone.0028126

Cited by 26 publications

(31 citation statements)

References 44 publications

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“…A single cross-sectional study investigating the association between anti- Pv SERA4 responses and P. vivax infection showed that both IgG and IgM responders had higher odds of P. vivax detected by light microscopy compared with non-responders (OR = 1.80, 95% CI 0.84 to 3.86, Figure 8 and OR = 2.50, 95% CI 1.39 to 4.49, respectively) [39]. …”

Section: Resultsmentioning

confidence: 99%

“…This may explain, in part, the differences observed, because in both studies, time of residence in the malaria-endemic area was positively correlated with the anti- Pv MSP-9 response [24,26]. Differential effects according to transmission were also anecdotally observed: one study by Yidez-Zeyrek et al in Turkey [39] showed greater magnitudes of effect with IgM than with IgG responses ( Pv MSP-1 19 and Pv SERA4), indicating that individuals living in this P. vivax -endemic area had limited exposure to P. vivax . Interestingly, the ability of IgG to serve as a marker of exposure in this study was more than twice that of estimates from areas of higher P. vivax transmission (in Brazil and PNG), highlighting the potential for transmission intensity to influence results.…”

Section: Discussionmentioning

confidence: 99%

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Immunological markers of Plasmodium vivaxexposure and immunity: a systematic review and meta-analysis

Cutts

Powell

Agius

et al. 2014

BMC Med

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BackgroundIdentifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations.MethodsWe performed a systematic review with meta-analysis of population-based, cross-sectional, case–control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria.ResultsThe majority of studies were published in South America (all from Brazil) and the rest from geographically diverse areas in the Asia-Pacific region. Considerable heterogeneity in estimates was observed, but IgG responses to PvCSP, PvMSP-119, PvMSP-9RIRII, and PvAMA1 were associated with increased odds of P. vivax infection in geographically diverse populations. Potential sources of heterogeneity included study design, different transmission intensities and transmigrant populations. Protective associations were observed for antibodies to PvMSP-119, PvMSP-1NT, PvMSP-3α and PvMSP-9NT antigens, but only in single geographical locations.ConclusionsThis systematic review revealed several antigen-specific antibodies that were associated with active infection and protective immunity, which may be useful biomarkers. However, more studies are needed on additional antigens, particularly cohort studies to increase the body of evidence for protective immunity. More studies representing diverse geographical regions encompassing varying P. vivax endemicities are needed to validate the generalizability of the findings and to provide a solid evidence base for the use of P. vivax antigens in vaccines and serosurveillance tools.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0150-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunological markers of Plasmodium vivaxexposure and immunity: a systematic review and meta-analysis

Cutts

Powell

Agius

et al. 2014

BMC Med

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“…Both IgG1 and IgG3 subclasses are cytophilic, T-cell dependent, and bind strongly to Fcγ, mediating phagocyte activation and complement fixation [ 30 , 31 ], and predominance of IgG1 and/or IgG3, in variable ratios, is common for several P . vivax [ 32 – 34 ] and P . falciparum merozoite proteins [ 35 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children

França

Gruszczyk

et al. 2016

PLoS Negl Trop Dis

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BackgroundMajor gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity.Methodology/Principal findingsWe assessed the binding specificity of five members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2-P2 and a non-binding fragment of PvRBP2c) to normocytes or reticulocytes. PvRBP2b was identified as the only reticulocyte-specific binder (P<0.001), whereas the others preferentially bound to normocytes (PvRBP1a/b P≤0.034), or showed comparable binding to both (PvRBP2a/2-P2, P = 0.38). Furthermore, we measured levels of total and IgG subclasses 1, 2, 3 and 4 to the six PvRBPs in a cohort of young Papua New Guinean children, and assessed their relationship with prospective risk of P. vivax malaria. Children had substantial, highly correlated (rho = 0.49–0.82, P<0.001) antibody levels to all six PvRBPs, with dominant IgG1 and IgG3 subclasses. Both total IgG (Incidence Rate Ratio [IRR] 0.63–0.73, P = 0.008–0.041) and IgG1 (IRR 0.56–0.69, P = 0.001–0.035) to PvRBP2b and PvRBP1a were strongly associated with reduced risk of vivax-malaria, independently of age and exposure.Conclusion/SignificanceThese results demonstrate a diversity of erythrocyte-binding phenotypes of PvRBPs, indicating binding to both reticulocyte-specific and normocyte-specific ligands. Our findings provide further insights into the naturally acquired immunity to P. vivax and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in P. vivax invasion and functional validation of the role of anti-PvRBP antibodies in clinical immunity against P. vivax are now required to confirm the potential of the reticulocyte-binding PvRBP2b and PvRBP1a as vaccine candidate antigens.

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“…Antibodies to PvAMA1 are also associated with P. vivax exposure (Yildiz Zeyrek et al. 2011 ; Fowkes et al. 2012 ), and antibodies to PvAMA1 have been shown to inhibit merozoite invasion in vitro (Vicentin et al.…”

Section: Introductionmentioning

confidence: 99%

“…PvSERA4, which is the most dominantly expressed member of the P. vivax SERA multigene family with an expression profile similar to PfSERA5, has also been shown to stimulate antibody responses (Yildiz Zeyrek et al. 2011 ), but no evidence for functional or protective responses is reported. Antibodies from naturally exposed individuals recognize P. vivax merozoite surface antigens representing polymorphic (PvMSP1 N-terminus, PvMSP3α Block I and II repeats, PvMSP5) and conserved regions (PvMSP1 19 , the extreme N- and C-terminal ends of PvMSP3α and PvMSP10) (Pasay et al.…”

Section: Introductionmentioning

confidence: 99%

Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

Beeson¹,

Drew²,

Boyle³

et al. 2016

FEMS Microbiology Reviews

305

277

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Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities.

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Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax

Cited by 26 publications

References 44 publications

Immunological markers of Plasmodium vivaxexposure and immunity: a systematic review and meta-analysis

Immunological markers of Plasmodium vivaxexposure and immunity: a systematic review and meta-analysis

Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children

Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

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