Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity

A more sensitive surveillance tool is needed to identify Plasmodium vivax infections for treatment and to accelerate malaria elimination efforts. To address this challenge, our laboratory has developed an eight-antigen panel that detects total IgG as serological markers of P. vivax exposure within t...

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Main Authors: Yanie Tayipto, Jason Rosado, Dionicia Gamboa, Michael T. White, Benson Kiniboro, Julie Healer, D. Herbert Opi, James G. Beeson, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Leanne Robinson, Ivo Mueller, Rhea J. Longley
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.950909/full
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author Yanie Tayipto
Yanie Tayipto
Jason Rosado
Dionicia Gamboa
Michael T. White
Benson Kiniboro
Julie Healer
D. Herbert Opi
D. Herbert Opi
D. Herbert Opi
James G. Beeson
James G. Beeson
James G. Beeson
James G. Beeson
Eizo Takashima
Takafumi Tsuboi
Matthias Harbers
Matthias Harbers
Leanne Robinson
Leanne Robinson
Ivo Mueller
Ivo Mueller
Rhea J. Longley
Rhea J. Longley
author_facet Yanie Tayipto
Yanie Tayipto
Jason Rosado
Dionicia Gamboa
Michael T. White
Benson Kiniboro
Julie Healer
D. Herbert Opi
D. Herbert Opi
D. Herbert Opi
James G. Beeson
James G. Beeson
James G. Beeson
James G. Beeson
Eizo Takashima
Takafumi Tsuboi
Matthias Harbers
Matthias Harbers
Leanne Robinson
Leanne Robinson
Ivo Mueller
Ivo Mueller
Rhea J. Longley
Rhea J. Longley
author_sort Yanie Tayipto
collection DOAJ
description A more sensitive surveillance tool is needed to identify Plasmodium vivax infections for treatment and to accelerate malaria elimination efforts. To address this challenge, our laboratory has developed an eight-antigen panel that detects total IgG as serological markers of P. vivax exposure within the prior 9 months. The value of these markers has been established for use in areas with low transmission. In moderate–high transmission areas, there is evidence that total IgG is more long-lived than in areas with low transmission, resulting in poorer performance of these markers in these settings. Antibodies that are shorter-lived may be better markers of recent infection for use in moderate–high transmission areas. Using a multiplex assay, the antibody temporal kinetics of total IgG, IgG1, IgG3, and IgM against 29 P. vivax antigens were measured over 36 weeks following asymptomatic P. vivax infection in Papua New Guinean children (n = 31), from an area with moderate–high transmission intensity. IgG3 declined faster to background than total IgG, IgG1, and IgM. Based on these kinetics, IgG3 performance was then assessed for classifying recent exposure in a cohort of Peruvian individuals (n = 590; age 3–85 years) from an area of moderate transmission intensity. Using antibody responses against individual antigens, the highest performance of IgG3 in classifying recent P. vivax infections in the prior 9 months was to one of the Pv-fam-a proteins assessed (PVX_125728) (AUC = 0.764). Surprisingly, total IgG was overall a better marker of recent P. vivax infection, with the highest individual classification performance to RBP2b1986-2653 (PVX_094255) (AUC = 0.838). To understand the acquisition of IgG3 in this Peruvian cohort, relevant epidemiological factors were explored using a regression model. IgG3 levels were positively associated with increasing age, living in an area with (relatively) higher transmission intensity, and having three or more PCR-detected blood-stage P. vivax infections within the prior 13 months. Overall, we found that IgG3 did not have high accuracy for detecting recent exposure to P. vivax in the Peruvian cohort, with our data suggesting that this is due to the high levels of prior exposure required to acquire high IgG3 antibody levels.
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spelling doaj.art-ad39105bc8c14650936d186f0c4b5dbc2022-12-22T02:44:38ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-08-011210.3389/fcimb.2022.950909950909Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensityYanie Tayipto0Yanie Tayipto1Jason Rosado2Dionicia Gamboa3Michael T. White4Benson Kiniboro5Julie Healer6D. Herbert Opi7D. Herbert Opi8D. Herbert Opi9James G. Beeson10James G. Beeson11James G. Beeson12James G. Beeson13Eizo Takashima14Takafumi Tsuboi15Matthias Harbers16Matthias Harbers17Leanne Robinson18Leanne Robinson19Ivo Mueller20Ivo Mueller21Rhea J. Longley22Rhea J. Longley23Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, VIC, AustraliaUnité Malaria: Parasites et Hôtes, Département Parasites et Insectes Vecteurs, Institut Pasteur, Paris, FranceLaboratorio International Centers of Excellence for Malaria Research (ICEMR)-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, PeruUnité Malaria: Parasites et Hôtes, Département Parasites et Insectes Vecteurs, Institut Pasteur, Paris, FranceVector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New GuineaPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaLife Sciences, Burnet Institute, Melbourne, VIC, AustraliaDepartment of Immunology and Pathology, Monash University, Melbourne, VIC, AustraliaDepartment of Medicine, The Doherty Institute, The University of Melbourne, Melbourne, VIC, AustraliaLife Sciences, Burnet Institute, Melbourne, VIC, AustraliaDepartment of Immunology and Pathology, Monash University, Melbourne, VIC, AustraliaDepartment of Medicine, The Doherty Institute, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Microbiology and Central Clinical School, Monash University, Clayton, VIC, Australia0Proteo-Science Center, Ehime University, Matsuyama, Japan0Proteo-Science Center, Ehime University, Matsuyama, Japan1CellFree Sciences Co., Ltd., Yokohama, Japan2RIKEN Centre for Integrative Medical Sciences, Yokohama, JapanPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaLife Sciences, Burnet Institute, Melbourne, VIC, AustraliaPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, VIC, AustraliaPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, VIC, AustraliaA more sensitive surveillance tool is needed to identify Plasmodium vivax infections for treatment and to accelerate malaria elimination efforts. To address this challenge, our laboratory has developed an eight-antigen panel that detects total IgG as serological markers of P. vivax exposure within the prior 9 months. The value of these markers has been established for use in areas with low transmission. In moderate–high transmission areas, there is evidence that total IgG is more long-lived than in areas with low transmission, resulting in poorer performance of these markers in these settings. Antibodies that are shorter-lived may be better markers of recent infection for use in moderate–high transmission areas. Using a multiplex assay, the antibody temporal kinetics of total IgG, IgG1, IgG3, and IgM against 29 P. vivax antigens were measured over 36 weeks following asymptomatic P. vivax infection in Papua New Guinean children (n = 31), from an area with moderate–high transmission intensity. IgG3 declined faster to background than total IgG, IgG1, and IgM. Based on these kinetics, IgG3 performance was then assessed for classifying recent exposure in a cohort of Peruvian individuals (n = 590; age 3–85 years) from an area of moderate transmission intensity. Using antibody responses against individual antigens, the highest performance of IgG3 in classifying recent P. vivax infections in the prior 9 months was to one of the Pv-fam-a proteins assessed (PVX_125728) (AUC = 0.764). Surprisingly, total IgG was overall a better marker of recent P. vivax infection, with the highest individual classification performance to RBP2b1986-2653 (PVX_094255) (AUC = 0.838). To understand the acquisition of IgG3 in this Peruvian cohort, relevant epidemiological factors were explored using a regression model. IgG3 levels were positively associated with increasing age, living in an area with (relatively) higher transmission intensity, and having three or more PCR-detected blood-stage P. vivax infections within the prior 13 months. Overall, we found that IgG3 did not have high accuracy for detecting recent exposure to P. vivax in the Peruvian cohort, with our data suggesting that this is due to the high levels of prior exposure required to acquire high IgG3 antibody levels.https://www.frontiersin.org/articles/10.3389/fcimb.2022.950909/fullmalariaPlasmodium vivaxmultiplex assaysurveillancemalaria eliminationantibody
spellingShingle Yanie Tayipto
Yanie Tayipto
Jason Rosado
Dionicia Gamboa
Michael T. White
Benson Kiniboro
Julie Healer
D. Herbert Opi
D. Herbert Opi
D. Herbert Opi
James G. Beeson
James G. Beeson
James G. Beeson
James G. Beeson
Eizo Takashima
Takafumi Tsuboi
Matthias Harbers
Matthias Harbers
Leanne Robinson
Leanne Robinson
Ivo Mueller
Ivo Mueller
Rhea J. Longley
Rhea J. Longley
Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
Frontiers in Cellular and Infection Microbiology
malaria
Plasmodium vivax
multiplex assay
surveillance
malaria elimination
antibody
title Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
title_full Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
title_fullStr Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
title_full_unstemmed Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
title_short Assessment of IgG3 as a serological exposure marker for Plasmodium vivax in areas with moderate–high malaria transmission intensity
title_sort assessment of igg3 as a serological exposure marker for plasmodium vivax in areas with moderate high malaria transmission intensity
topic malaria
Plasmodium vivax
multiplex assay
surveillance
malaria elimination
antibody
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.950909/full
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