Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Wellcome Open Research ◽

10.12688/wellcomeopenres.15919.2 ◽

2021 ◽

Vol 5 ◽

pp. 136

Author(s):

Tony I. Isebe ◽

Joel L. Bargul ◽

Bonface M. Gichuki ◽

James M. Njunge ◽

James Tuju ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Negative Correlation ◽

The Gambia ◽

Antibody Responses ◽

Transmission Intensity ◽

Parasite Development ◽

Malaria Transmission Intensity ◽

Transmission Region ◽

Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in Gambia, compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses indicate negative correlation between antibody levels and malaria transmission intensity for Pf3D7_1102500 and Pf3D7_1401600. We report a correlation in antibody responses between schizont and gametocyte extract, but this is not statistically significant (cor=0.102, p=0.2851, CI=95%) and, Pf3D7_0532400 (cor=0.11, p=0.249, CI=95%) and Pf3D7_1401600 (cor=0.02, p=0.7968, CI=95%). We report a negative correlation in antibody responses between schizont and Pf3D7_1102500 (cor=-0.008, p=0.9348, CI=95%). There is a correlation between gametocyte extract and Pf3D7_1401600 (cor=-0.0402, p=0.6735, CI=95%), Pf3D7_1102500 (cor=0.0758, p=0.4271, CI=95%) and Pf3D7_0532400 (cor=0.155, p=0.1028, CI=95%). Acquisition of anti-PHIST antibodies correlates with exposure to malaria for Pf3D7_0532400 (p=0.009) but not Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels which do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore their potential as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Evaluation of malaria transmission intensity using antibody responses to Plasmodium falciparum merozoite surface protein-119 after vector control in western Kenya

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00277 ◽

2013 ◽

Vol 4 ◽

Author(s):

Awandu Shehu ◽

Gicheru Michael ◽

Kariuki Simon

Keyword(s):

Plasmodium Falciparum ◽

Vector Control ◽

Malaria Transmission ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Antibody Responses ◽

Transmission Intensity ◽

Western Kenya ◽

Malaria Transmission Intensity ◽

Falciparum Merozoite

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Estimating malaria transmission intensity from Plasmodium falciparum serological data using antibody density models

Malaria Journal ◽

10.1186/s12936-016-1121-0 ◽

2016 ◽

Vol 15 (1) ◽

Cited By ~ 22

Author(s):

Emilie Pothin ◽

Neil M. Ferguson ◽

Chris J. Drakeley ◽

Azra C. Ghani

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Transmission Intensity ◽

Malaria Transmission Intensity ◽

Serological Data

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Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.15-0710 ◽

2016 ◽

Vol 95 (3) ◽

pp. 580-587 ◽

Cited By ~ 2

Author(s):

Natalie M. Bowman ◽

Chandy C. John ◽

Ann M. Moormann ◽

Jonathan J. Juliano ◽

John Vulule ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Immune Responses ◽

Malaria Transmission ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Transmission Intensity ◽

Malaria Transmission Intensity ◽

Merozoite Surface Protein 1 ◽

Falciparum Merozoite

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The Diversity, Multiplicity of Infection and Population Structure of P. falciparum Parasites Circulating in Asymptomatic Carriers Living in High and Low Malaria Transmission Settings of Ghana

Genes ◽

10.3390/genes10060434 ◽

2019 ◽

Vol 10 (6) ◽

pp. 434 ◽

Cited By ~ 8

Author(s):

Zakaria Abukari ◽

Ruth Okonu ◽

Samuel B. Nyarko ◽

Aminata C. Lo ◽

Cheikh C. Dieng ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Population Structure ◽

Malaria Transmission ◽

Parasite Prevalence ◽

Transmission Intensity ◽

Multiplicity Of Infection ◽

Malaria Transmission Intensity ◽

Ms Analysis ◽

Greater Accra Region ◽

Low Malaria Transmission

Background: Diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. This study utilized 12 polymorphic microsatellite (MS) markers and the Msp2 marker to examine diversity, multiplicity of infection (MOI) as well as the population structure of parasites circulating in two sites separated by about 92 km and with varying malaria transmission intensities within the Greater Accra Region of Ghana. Methods: The diversity and MOI of P. falciparum parasites in 160 non-symptomatic volunteers living in Obom (high malaria transmission intensity) and Asutsuare (low malaria transmission intensity) aged between 8 and 60 years was determined using Msp2 genotyping and microsatellite analysis. Results: The prevalence of asymptomatic P. falciparum carriers as well as the parasite density of infections was significantly higher in Obom than in Asutsuare. Samples from Asutsuare and Obom were 100% and 65% clonal, respectively, by Msp2 genotyping but decreased to 50% and 5%, respectively, when determined by MS analysis. The genetic composition of parasites from Obom and Asutsuare were highly distinct, with parasites from Obom being more diverse than those from Asutsuare. Conclusion: Plasmodium falciparum parasites circulating in Obom are genetically more diverse and distinct from those circulating in Asutsuare. The MOI in samples from both Obom and Asutsuare increased when assessed by MS analysis relative to MSP2 genotyping. The TA40 and TA87 loci are useful markers for estimating MOI in high and low parasite prevalence settings.

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Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration

BMC Medicine ◽

10.1186/s12916-020-01785-6 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Lindsey Wu ◽

Julia Mwesigwa ◽

Muna Affara ◽

Mamadou Bah ◽

Simon Correa ◽

...

Keyword(s):

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

West Coast ◽

Malaria Infection ◽

The Gambia ◽

Antibody Responses ◽

The West ◽

Conversion Rates ◽

Antibody Levels

Abstract Background As The Gambia aims to achieve malaria elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. Methods Within a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis. Results Seasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 years in two transmission settings—the West Coast and Upper River Regions (4.32% and 31.30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1–15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings from the Malaria Transmission Dynamics Study, where individuals infected before the implementation of MDA had two-fold higher odds of re-infection post-MDA. Conclusions Serological markers can serve dual functions as indicators of malaria exposure and incidence. By monitoring age-specific sero-prevalence, the magnitude of age-stratified antibody levels, or identifying groups of individuals with above-average antibody responses, these antigens have the potential to complement conventional malaria surveillance tools. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to reliably measure transmission across endemic settings.

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