Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants
Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine for...
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doaj-88b258c5464845de9d2f43aeadbc40d12021-03-16T15:23:55ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-03-011110.3389/fcimb.2021.616230616230Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide VariantsAna Caroline Barbosa França0Kátia Sanches Françoso1Rodolfo Ferreira Marques2Gustavo H. G. Trossini3Renan A. Gomes4Marinete M. Póvoa5Maristela G. Cunha6Eduardo L. V. Silveira7Irene S. Soares8Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilInstituto Evandro Chagas, Ananindeua, BrazilInstituto de Ciências Biológicas, Universidade Federal do Pará, Belém, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, BrazilMalaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria.https://www.frontiersin.org/articles/10.3389/fcimb.2021.616230/fullmalariaPlasmodium vivaxapical membrane antigen 1polymorphismvaccine |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Caroline Barbosa França Kátia Sanches Françoso Rodolfo Ferreira Marques Gustavo H. G. Trossini Renan A. Gomes Marinete M. Póvoa Maristela G. Cunha Eduardo L. V. Silveira Irene S. Soares |
spellingShingle |
Ana Caroline Barbosa França Kátia Sanches Françoso Rodolfo Ferreira Marques Gustavo H. G. Trossini Renan A. Gomes Marinete M. Póvoa Maristela G. Cunha Eduardo L. V. Silveira Irene S. Soares Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants Frontiers in Cellular and Infection Microbiology malaria Plasmodium vivax apical membrane antigen 1 polymorphism vaccine |
author_facet |
Ana Caroline Barbosa França Kátia Sanches Françoso Rodolfo Ferreira Marques Gustavo H. G. Trossini Renan A. Gomes Marinete M. Póvoa Maristela G. Cunha Eduardo L. V. Silveira Irene S. Soares |
author_sort |
Ana Caroline Barbosa França |
title |
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants |
title_short |
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants |
title_full |
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants |
title_fullStr |
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants |
title_full_unstemmed |
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants |
title_sort |
antibodies against the plasmodium vivax apical membrane antigen 1 from the belem strain share common epitopes among other worldwide variants |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2021-03-01 |
description |
Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria. |
topic |
malaria Plasmodium vivax apical membrane antigen 1 polymorphism vaccine |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2021.616230/full |
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