Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay

Memory B cells (MBCs) are believed to be important for the maintenance of immunity to malaria, and these cells need to be explored in the context of different parasite antigens and their breadth and kinetics after natural infections. However, frequencies of antigen-specific MBCs are low in periphera...

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Main Authors: Peter Jahnmatz, Christopher Sundling, Victor Yman, Linnea Widman, Muhammad Asghar, Klara Sondén, Christine Stenström, Christian Smedman, Francis Ndungu, Niklas Ahlborg, Anna Färnert
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.619398/full
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author Peter Jahnmatz
Peter Jahnmatz
Christopher Sundling
Christopher Sundling
Victor Yman
Linnea Widman
Muhammad Asghar
Muhammad Asghar
Klara Sondén
Klara Sondén
Christine Stenström
Christian Smedman
Francis Ndungu
Francis Ndungu
Niklas Ahlborg
Niklas Ahlborg
Anna Färnert
Anna Färnert
author_facet Peter Jahnmatz
Peter Jahnmatz
Christopher Sundling
Christopher Sundling
Victor Yman
Linnea Widman
Muhammad Asghar
Muhammad Asghar
Klara Sondén
Klara Sondén
Christine Stenström
Christian Smedman
Francis Ndungu
Francis Ndungu
Niklas Ahlborg
Niklas Ahlborg
Anna Färnert
Anna Färnert
author_sort Peter Jahnmatz
collection DOAJ
description Memory B cells (MBCs) are believed to be important for the maintenance of immunity to malaria, and these cells need to be explored in the context of different parasite antigens and their breadth and kinetics after natural infections. However, frequencies of antigen-specific MBCs are low in peripheral blood, limiting the number of antigens that can be studied, especially when small blood volumes are available. Here, we developed a multiplexed reversed B-cell FluoroSpot assay capable of simultaneously detecting MBCs specific for the four Plasmodium falciparum blood-stage antigens, MSP-119, MSP-2, MSP-3 and AMA-1. We used the assay to study the kinetics of the MBC response after an acute episode of malaria and up to one year following treatment in travelers returning to Sweden from sub-Saharan Africa. We show that the FluoroSpot assay can detect MBCs to all four merozoite antigens in the same well, and that the breadth and kinetics varied between individuals. We further found that individuals experiencing a primary infection could mount and maintain parasite-specific MBCs to a similar extent as previously exposed adults, already after a single infection. We conclude that the multiplexed B-cell FluoroSpot is a powerful tool for assessing antigen-specific MBC responses to several antigens simultaneously, and that the kinetics of MBC responses against merozoite surface antigens differ over the course of one year. These findings contribute to the understanding of acquisition and maintenance of immune responses to malaria.
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spelling doaj.art-30aa72b264714114ac722d04144f08c52022-12-21T22:36:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.619398619398Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot AssayPeter Jahnmatz0Peter Jahnmatz1Christopher Sundling2Christopher Sundling3Victor Yman4Linnea Widman5Muhammad Asghar6Muhammad Asghar7Klara Sondén8Klara Sondén9Christine Stenström10Christian Smedman11Francis Ndungu12Francis Ndungu13Niklas Ahlborg14Niklas Ahlborg15Anna Färnert16Anna Färnert17Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenMabtech AB, Nacka Strand, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenDepartment of Infectious Diseases, Karolinska University Hospital, Stockholm, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenDivision of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenDepartment of Infectious Diseases, Karolinska University Hospital, Stockholm, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenDepartment of Infectious Diseases, Karolinska University Hospital, Stockholm, SwedenDepartment of Clinical Microbiology, Karolinska University Hospital, Stockholm, SwedenMabtech AB, Nacka Strand, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenKenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi, KenyaMabtech AB, Nacka Strand, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Stockholm, SwedenDepartment of Infectious Diseases, Karolinska University Hospital, Stockholm, SwedenMemory B cells (MBCs) are believed to be important for the maintenance of immunity to malaria, and these cells need to be explored in the context of different parasite antigens and their breadth and kinetics after natural infections. However, frequencies of antigen-specific MBCs are low in peripheral blood, limiting the number of antigens that can be studied, especially when small blood volumes are available. Here, we developed a multiplexed reversed B-cell FluoroSpot assay capable of simultaneously detecting MBCs specific for the four Plasmodium falciparum blood-stage antigens, MSP-119, MSP-2, MSP-3 and AMA-1. We used the assay to study the kinetics of the MBC response after an acute episode of malaria and up to one year following treatment in travelers returning to Sweden from sub-Saharan Africa. We show that the FluoroSpot assay can detect MBCs to all four merozoite antigens in the same well, and that the breadth and kinetics varied between individuals. We further found that individuals experiencing a primary infection could mount and maintain parasite-specific MBCs to a similar extent as previously exposed adults, already after a single infection. We conclude that the multiplexed B-cell FluoroSpot is a powerful tool for assessing antigen-specific MBC responses to several antigens simultaneously, and that the kinetics of MBC responses against merozoite surface antigens differ over the course of one year. These findings contribute to the understanding of acquisition and maintenance of immune responses to malaria.https://www.frontiersin.org/articles/10.3389/fimmu.2020.619398/fullantibodymemory B-cellFluoroSpotP. falciparum malariarecombinant proteins
spellingShingle Peter Jahnmatz
Peter Jahnmatz
Christopher Sundling
Christopher Sundling
Victor Yman
Linnea Widman
Muhammad Asghar
Muhammad Asghar
Klara Sondén
Klara Sondén
Christine Stenström
Christian Smedman
Francis Ndungu
Francis Ndungu
Niklas Ahlborg
Niklas Ahlborg
Anna Färnert
Anna Färnert
Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
Frontiers in Immunology
antibody
memory B-cell
FluoroSpot
P. falciparum malaria
recombinant proteins
title Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
title_full Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
title_fullStr Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
title_full_unstemmed Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
title_short Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay
title_sort memory b cell responses against merozoite antigens after acute plasmodium falciparum malaria assessed over one year using a novel multiplexed fluorospot assay
topic antibody
memory B-cell
FluoroSpot
P. falciparum malaria
recombinant proteins
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.619398/full
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