Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon

Antibodies have an essential role in the acquired immune response against blood stage P. falciparum infection. Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodie...

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Veröffentlicht in:BMC infectious diseases 2013-12, Vol.13 (1), p.608-608, Article 608
Hauptverfasser: Medeiros, Márcia M, Fotoran, Wesley L, dalla Martha, Rosimeire C, Katsuragawa, Tony H, Pereira da Silva, Luiz Hildebrando, Wunderlich, Gerhard
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container_title BMC infectious diseases
container_volume 13
creator Medeiros, Márcia M
Fotoran, Wesley L
dalla Martha, Rosimeire C
Katsuragawa, Tony H
Pereira da Silva, Luiz Hildebrando
Wunderlich, Gerhard
description Antibodies have an essential role in the acquired immune response against blood stage P. falciparum infection. Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens. Specific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulating P. falciparum field isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients' plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas. 11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2(DF=1) = 9.26/p = 0.0047) and MSP5 (X2(DF=1) = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2(DF=1) = 6.41/p = 0.0206, Fisher's exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5, p 
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Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens. Specific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulating P. falciparum field isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients' plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas. 11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2(DF=1) = 9.26/p = 0.0047) and MSP5 (X2(DF=1) = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2(DF=1) = 6.41/p = 0.0206, Fisher's exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5, p &lt; 0.03), MSP5 (U = 212, p &lt; 0.004), MSP9 (U = 189.5, p &lt; 0.002) and EBA175 (U = 197, p &lt; 0.014, Mann-Whitney's U test). IgG1 and IgG3 were predominant for all antigens, but some patients also presented with IgG2 and IgG4. The recognition of MSP5 (OR = 0.112, IC95% = 0.021-0.585) and MSP9 (OR = 0.125, IC95% = 0.030-0.529, cross tab analysis) predicted 8.9 and 8 times less chances, respectively, to present symptoms. Higher antibody levels against MSP5 and EBA175 were associated by odds ratios of 9.4 (IC95% = 1.29-69.25) and 5.7 (IC95% = 1.12-29.62, logistic regression), respectively, with an asymptomatic status. Merozoite antigens were targets of cytophilic antibodies and antibodies against MSP5, MSP9 and EBA175 were independently associated with decreased symptoms.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/1471-2334-13-608</identifier><identifier>PMID: 24373342</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Antibodies ; Antibodies, Protozoan - blood ; Antibodies, Protozoan - immunology ; Antigen-antibody reactions ; Antigens ; Antigens, Protozoan - blood ; Antigens, Protozoan - immunology ; Blood ; Brazil ; Care and treatment ; Cross Protection ; Enzyme-Linked Immunosorbent Assay ; Erythrocytes ; Female ; Health aspects ; Humans ; Immune response ; Immunoglobulin G ; Ligands ; Malaria ; Malaria, Falciparum - blood ; Malaria, Falciparum - immunology ; Malaria, Falciparum - parasitology ; Malaria, Falciparum - prevention &amp; control ; Male ; Membrane Proteins - blood ; Membrane Proteins - immunology ; Middle Aged ; Mortality ; Parasites ; Plasmodium falciparum ; Plasmodium falciparum - genetics ; Plasmodium falciparum - immunology ; Plasmodium falciparum - isolation &amp; purification ; Proteins ; Protozoan Proteins - blood ; Protozoan Proteins - immunology ; Risk factors ; Vaccines ; Viral antibodies</subject><ispartof>BMC infectious diseases, 2013-12, Vol.13 (1), p.608-608, Article 608</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Medeiros et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Medeiros et al.; licensee BioMed Central Ltd. 2013 Medeiros et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b652t-a525f666228e2ba772d9d6a67ecd458df303b23ed0be87e8882e46a7ac0e9ed73</citedby><cites>FETCH-LOGICAL-b652t-a525f666228e2ba772d9d6a67ecd458df303b23ed0be87e8882e46a7ac0e9ed73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880555/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880555/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24373342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Medeiros, Márcia M</creatorcontrib><creatorcontrib>Fotoran, Wesley L</creatorcontrib><creatorcontrib>dalla Martha, Rosimeire C</creatorcontrib><creatorcontrib>Katsuragawa, Tony H</creatorcontrib><creatorcontrib>Pereira da Silva, Luiz Hildebrando</creatorcontrib><creatorcontrib>Wunderlich, Gerhard</creatorcontrib><title>Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>Antibodies have an essential role in the acquired immune response against blood stage P. falciparum infection. Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens. Specific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulating P. falciparum field isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients' plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas. 11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2(DF=1) = 9.26/p = 0.0047) and MSP5 (X2(DF=1) = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2(DF=1) = 6.41/p = 0.0206, Fisher's exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5, p &lt; 0.03), MSP5 (U = 212, p &lt; 0.004), MSP9 (U = 189.5, p &lt; 0.002) and EBA175 (U = 197, p &lt; 0.014, Mann-Whitney's U test). IgG1 and IgG3 were predominant for all antigens, but some patients also presented with IgG2 and IgG4. The recognition of MSP5 (OR = 0.112, IC95% = 0.021-0.585) and MSP9 (OR = 0.125, IC95% = 0.030-0.529, cross tab analysis) predicted 8.9 and 8 times less chances, respectively, to present symptoms. Higher antibody levels against MSP5 and EBA175 were associated by odds ratios of 9.4 (IC95% = 1.29-69.25) and 5.7 (IC95% = 1.12-29.62, logistic regression), respectively, with an asymptomatic status. Merozoite antigens were targets of cytophilic antibodies and antibodies against MSP5, MSP9 and EBA175 were independently associated with decreased symptoms.</description><subject>Antibodies</subject><subject>Antibodies, Protozoan - blood</subject><subject>Antibodies, Protozoan - immunology</subject><subject>Antigen-antibody reactions</subject><subject>Antigens</subject><subject>Antigens, Protozoan - blood</subject><subject>Antigens, Protozoan - immunology</subject><subject>Blood</subject><subject>Brazil</subject><subject>Care and treatment</subject><subject>Cross Protection</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunoglobulin G</subject><subject>Ligands</subject><subject>Malaria</subject><subject>Malaria, Falciparum - blood</subject><subject>Malaria, Falciparum - immunology</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Malaria, Falciparum - prevention &amp; control</subject><subject>Male</subject><subject>Membrane Proteins - blood</subject><subject>Membrane Proteins - immunology</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Parasites</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - genetics</subject><subject>Plasmodium falciparum - immunology</subject><subject>Plasmodium falciparum - isolation &amp; purification</subject><subject>Proteins</subject><subject>Protozoan Proteins - blood</subject><subject>Protozoan Proteins - immunology</subject><subject>Risk factors</subject><subject>Vaccines</subject><subject>Viral antibodies</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNk11rFDEUhgdRbK3eeyUBbxScmo-ZJHMjbJeqhWqLVW9DJnN2mzKTrElG7P4Sf64Zt9auVCiBJJw875uTc0hRPCV4nxDJX5NKkJIyVpWElRzLe8Xudej-jf1O8SjGC4yJkLR5WOzQiokcprvFz486jUH3SLtkW99dogBx5V0ElDw67XUcfGfHAS10b-xKh7wdIPi1twl-i5bgIvpwdlq_muYmxzp0eDAjokY2Ih2jN1Yn6CY_01tnTb5tFXwCk6x3yDqUzgEdBL22vdUOzQa99u5x8SBfGeHJ1bpXfHl7-Hn-vjw-eXc0nx2XLa9pKnVN6wXnnFIJtNVC0K7puOYCTFfVslswzFrKoMMtSAFSSgoV10IbDA10gu0Vbza-q7EdoDPgUi6HWgU76HCpvLZq-8TZc7X03xWTEtd1nQ3mG4PW-v8YbJ8YP6ipM2rqjCJM5cZllxdXaQT_bYSY1GCjgb7XDvwYs6Ch-ZE1FndBMW8Ekzyjz_9BL_wYXK7nlEFFMOeE_KWWugdl3cLnPM1kqmY1q3J6uJmo_VuoPDoYrPEOFjbHtwQvtwSZSfAjLfUYozo6-3R39uTrNos3rAk-xgCL61oTrKZvcVt1n91s8rXgzz9gvwBX4AZZ</recordid><startdate>20131228</startdate><enddate>20131228</enddate><creator>Medeiros, Márcia M</creator><creator>Fotoran, Wesley L</creator><creator>dalla Martha, Rosimeire C</creator><creator>Katsuragawa, Tony H</creator><creator>Pereira da Silva, Luiz Hildebrando</creator><creator>Wunderlich, Gerhard</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T2</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope></search><sort><creationdate>20131228</creationdate><title>Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon</title><author>Medeiros, Márcia M ; 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Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens. Specific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulating P. falciparum field isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients' plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas. 11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2(DF=1) = 9.26/p = 0.0047) and MSP5 (X2(DF=1) = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2(DF=1) = 6.41/p = 0.0206, Fisher's exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5, p &lt; 0.03), MSP5 (U = 212, p &lt; 0.004), MSP9 (U = 189.5, p &lt; 0.002) and EBA175 (U = 197, p &lt; 0.014, Mann-Whitney's U test). IgG1 and IgG3 were predominant for all antigens, but some patients also presented with IgG2 and IgG4. The recognition of MSP5 (OR = 0.112, IC95% = 0.021-0.585) and MSP9 (OR = 0.125, IC95% = 0.030-0.529, cross tab analysis) predicted 8.9 and 8 times less chances, respectively, to present symptoms. Higher antibody levels against MSP5 and EBA175 were associated by odds ratios of 9.4 (IC95% = 1.29-69.25) and 5.7 (IC95% = 1.12-29.62, logistic regression), respectively, with an asymptomatic status. Merozoite antigens were targets of cytophilic antibodies and antibodies against MSP5, MSP9 and EBA175 were independently associated with decreased symptoms.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24373342</pmid><doi>10.1186/1471-2334-13-608</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Antibodies
Antibodies, Protozoan - blood
Antibodies, Protozoan - immunology
Antigen-antibody reactions
Antigens
Antigens, Protozoan - blood
Antigens, Protozoan - immunology
Blood
Brazil
Care and treatment
Cross Protection
Enzyme-Linked Immunosorbent Assay
Erythrocytes
Female
Health aspects
Humans
Immune response
Immunoglobulin G
Ligands
Malaria
Malaria, Falciparum - blood
Malaria, Falciparum - immunology
Malaria, Falciparum - parasitology
Malaria, Falciparum - prevention & control
Male
Membrane Proteins - blood
Membrane Proteins - immunology
Middle Aged
Mortality
Parasites
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Plasmodium falciparum - isolation & purification
Proteins
Protozoan Proteins - blood
Protozoan Proteins - immunology
Risk factors
Vaccines
Viral antibodies
title Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon
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