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Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens
No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induc...
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Published in: | PLoS pathogens 2012-11, Vol.8 (11), p.e1002991-e1002991 |
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creator | Williams, Andrew R Douglas, Alexander D Miura, Kazutoyo Illingworth, Joseph J Choudhary, Prateek Murungi, Linda M Furze, Julie M Diouf, Ababacar Miotto, Olivo Crosnier, Cécile Wright, Gavin J Kwiatkowski, Dominic P Fairhurst, Rick M Long, Carole A Draper, Simon J |
description | No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines. |
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We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1002991</identifier><identifier>PMID: 23144611</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antibodies, Monoclonal, Murine-Derived - immunology ; Antibodies, Protozoan - immunology ; Antigens ; Antigens, Protozoan - immunology ; Biology ; Carrier Proteins - immunology ; Erythrocytes ; Erythrocytes - immunology ; Erythrocytes - parasitology ; Health aspects ; Humans ; Malaria ; Malaria Vaccines - immunology ; Malaria, Falciparum - immunology ; Malaria, Falciparum - prevention & control ; Medicine ; Merozoites - immunology ; Mice ; Parasites ; Physiological aspects ; Plasmodium falciparum ; Plasmodium falciparum - immunology ; Proteins ; Protozoan Proteins - immunology ; Vaccines ; Viral antibodies</subject><ispartof>PLoS pathogens, 2012-11, Vol.8 (11), p.e1002991-e1002991</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Williams AR, Douglas AD, Miura K, Illingworth JJ, Choudhary P, et al. (2012) Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens. PLoS Pathog 8(11): e1002991. doi:10.1371/journal.ppat.1002991</rights><rights>2012</rights><rights>2012 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Williams AR, Douglas AD, Miura K, Illingworth JJ, Choudhary P, et al. (2012) Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens. PLoS Pathog 8(11): e1002991. doi:10.1371/journal.ppat.1002991</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c727t-6fa0584f07cc07d5425bded7009c3099eb5a3cc9bcc7232985a95bc6b5fc2ca63</citedby><cites>FETCH-LOGICAL-c727t-6fa0584f07cc07d5425bded7009c3099eb5a3cc9bcc7232985a95bc6b5fc2ca63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289112674/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289112674?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23144611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Riley, Eleanor M.</contributor><creatorcontrib>Williams, Andrew R</creatorcontrib><creatorcontrib>Douglas, Alexander D</creatorcontrib><creatorcontrib>Miura, Kazutoyo</creatorcontrib><creatorcontrib>Illingworth, Joseph J</creatorcontrib><creatorcontrib>Choudhary, Prateek</creatorcontrib><creatorcontrib>Murungi, Linda M</creatorcontrib><creatorcontrib>Furze, Julie M</creatorcontrib><creatorcontrib>Diouf, Ababacar</creatorcontrib><creatorcontrib>Miotto, Olivo</creatorcontrib><creatorcontrib>Crosnier, Cécile</creatorcontrib><creatorcontrib>Wright, Gavin J</creatorcontrib><creatorcontrib>Kwiatkowski, Dominic P</creatorcontrib><creatorcontrib>Fairhurst, Rick M</creatorcontrib><creatorcontrib>Long, Carole A</creatorcontrib><creatorcontrib>Draper, Simon J</creatorcontrib><title>Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal, Murine-Derived - immunology</subject><subject>Antibodies, Protozoan - immunology</subject><subject>Antigens</subject><subject>Antigens, Protozoan - immunology</subject><subject>Biology</subject><subject>Carrier Proteins - immunology</subject><subject>Erythrocytes</subject><subject>Erythrocytes - immunology</subject><subject>Erythrocytes - parasitology</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Malaria</subject><subject>Malaria Vaccines - immunology</subject><subject>Malaria, Falciparum - immunology</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Medicine</subject><subject>Merozoites - immunology</subject><subject>Mice</subject><subject>Parasites</subject><subject>Physiological aspects</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - immunology</subject><subject>Proteins</subject><subject>Protozoan Proteins - immunology</subject><subject>Vaccines</subject><subject>Viral antibodies</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqVk81u1DAQgCMEomXhDRBE4gKHXfybrDkgVVWhK1VQFThbE8fJeknsxXYqlrfgjXHYtOqiXlAOscbffOMZabLsOUYLTEv8duMGb6FbbLcQFxghIgR-kB1jzum8pCV7eOd8lD0JYYMQwxQXj7MjQjFjBcbH2e8zuwarjG3zqnPqO9Q6d01-2UHoXW2GPm-gU2YLPh2138W1d2oXdW7sNQTj7LscQtAhjAbl-spYiCkcRgvYaKpk0SGHFowNMb9srs55uqhzF9fa57327pczSTjCrbbhafYolQz62fSfZd8-nH09PZ9ffP64Oj25mKuSlHFeNID4kjWoVAqVNWeEV7WuS4SEokgIXXGgSolKJZ4SseQgeKWKijeKKCjoLHu59247F-Q0zSAxWQqMSVGyRKz2RO1gI7fe9OB30oGRfwPOtxJ8NKrTEnMKgHFTa1UxyquKCVzgNMxGFUKrZXK9n6oNVa9rpW300B1ID2-sWcvWXUvKBGWpg1n2ehJ492PQIcreBKW7Dqx2Q3o35lgQJghP6Kt_0Pu7m6gWUgPGNi7VVaNUnlBMMCqWRCRqcQ-Vvlr3RjmrG5PiBwlvDhISE_XP2MIQglx9ufoP9tMhy_as8i4Er5vb2WEkx4W4aVKOCyGnhUhpL-7O_TbpZgPoH916Cno</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>Williams, Andrew R</creator><creator>Douglas, Alexander D</creator><creator>Miura, Kazutoyo</creator><creator>Illingworth, Joseph J</creator><creator>Choudhary, Prateek</creator><creator>Murungi, Linda M</creator><creator>Furze, Julie M</creator><creator>Diouf, Ababacar</creator><creator>Miotto, Olivo</creator><creator>Crosnier, Cécile</creator><creator>Wright, Gavin J</creator><creator>Kwiatkowski, Dominic P</creator><creator>Fairhurst, Rick M</creator><creator>Long, Carole A</creator><creator>Draper, Simon J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121101</creationdate><title>Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens</title><author>Williams, Andrew R ; Douglas, Alexander D ; Miura, Kazutoyo ; Illingworth, Joseph J ; Choudhary, Prateek ; Murungi, Linda M ; Furze, Julie M ; Diouf, Ababacar ; Miotto, Olivo ; Crosnier, Cécile ; Wright, Gavin J ; Kwiatkowski, Dominic P ; Fairhurst, Rick M ; Long, Carole A ; Draper, Simon J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c727t-6fa0584f07cc07d5425bded7009c3099eb5a3cc9bcc7232985a95bc6b5fc2ca63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal, Murine-Derived - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williams, Andrew R</au><au>Douglas, Alexander D</au><au>Miura, Kazutoyo</au><au>Illingworth, Joseph J</au><au>Choudhary, Prateek</au><au>Murungi, Linda M</au><au>Furze, Julie M</au><au>Diouf, Ababacar</au><au>Miotto, Olivo</au><au>Crosnier, Cécile</au><au>Wright, Gavin J</au><au>Kwiatkowski, Dominic P</au><au>Fairhurst, Rick M</au><au>Long, Carole A</au><au>Draper, Simon J</au><au>Riley, Eleanor M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>8</volume><issue>11</issue><spage>e1002991</spage><epage>e1002991</epage><pages>e1002991-e1002991</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23144611</pmid><doi>10.1371/journal.ppat.1002991</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies Antibodies, Monoclonal, Murine-Derived - immunology Antibodies, Protozoan - immunology Antigens Antigens, Protozoan - immunology Biology Carrier Proteins - immunology Erythrocytes Erythrocytes - immunology Erythrocytes - parasitology Health aspects Humans Malaria Malaria Vaccines - immunology Malaria, Falciparum - immunology Malaria, Falciparum - prevention & control Medicine Merozoites - immunology Mice Parasites Physiological aspects Plasmodium falciparum Plasmodium falciparum - immunology Proteins Protozoan Proteins - immunology Vaccines Viral antibodies |
title | Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens |
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