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T cell epitope regions of the P. falciparum MSP1-33 critically influence immune responses and in vitro efficacy of MSP1-42 vaccines
The C-terminal 42 kDa fragments of the P. falciparum Merozoite Surface Protein 1, MSP1-42 is a leading malaria vaccine candidate. MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave...
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Published in: | PloS one 2011-09, Vol.6 (9), p.e24782-e24782 |
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description | The C-terminal 42 kDa fragments of the P. falciparum Merozoite Surface Protein 1, MSP1-42 is a leading malaria vaccine candidate. MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave in vivo evidence that T cell epitope regions of MSP1-33 provide functional help in inducing anti-MSP1-19 antibodies. Eleven truncated MSP1-33 segments were expressed in tandem with MSP1-19, and immunogenicity was evaluated in Swiss Webster mice and New Zealand White rabbits. Analyses of anti-MSP1-19 antibody responses revealed striking differences in these segments' helper function despite that they all possess T cell epitopes. Only a few fragments induced a generalized response (100%) in outbred mice. These were comparable to or surpassed the responses observed with the full length MSP1-42. In rabbits, only a subset of truncated antigens induced potent parasite growth inhibitory antibodies. Notably, two constructs were more efficacious than MSP1-42, with one containing only conserved T cell epitopes. Moreover, another T cell epitope region induced high titers of non-inhibitory antibodies and they interfered with the inhibitory activities of anti-MSP1-42 antibodies. In mice, this region also induced a skewed TH2 cellular response. This is the first demonstration that T cell epitope regions of MSP1-33 positively or negatively influenced antibody responses. Differential recognition of these regions by humans may play critical roles in vaccine induced and/or natural immunity to MSP1-42. This study provides the rational basis to re-engineer more efficacious MSP1-42 vaccines by selective inclusion and exclusion of MSP1-33 specific T cell epitopes. |
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MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave in vivo evidence that T cell epitope regions of MSP1-33 provide functional help in inducing anti-MSP1-19 antibodies. Eleven truncated MSP1-33 segments were expressed in tandem with MSP1-19, and immunogenicity was evaluated in Swiss Webster mice and New Zealand White rabbits. Analyses of anti-MSP1-19 antibody responses revealed striking differences in these segments' helper function despite that they all possess T cell epitopes. Only a few fragments induced a generalized response (100%) in outbred mice. These were comparable to or surpassed the responses observed with the full length MSP1-42. In rabbits, only a subset of truncated antigens induced potent parasite growth inhibitory antibodies. Notably, two constructs were more efficacious than MSP1-42, with one containing only conserved T cell epitopes. Moreover, another T cell epitope region induced high titers of non-inhibitory antibodies and they interfered with the inhibitory activities of anti-MSP1-42 antibodies. In mice, this region also induced a skewed TH2 cellular response. This is the first demonstration that T cell epitope regions of MSP1-33 positively or negatively influenced antibody responses. Differential recognition of these regions by humans may play critical roles in vaccine induced and/or natural immunity to MSP1-42. This study provides the rational basis to re-engineer more efficacious MSP1-42 vaccines by selective inclusion and exclusion of MSP1-33 specific T cell epitopes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0024782</identifier><identifier>PMID: 21931852</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies ; Antibody response ; Antigenic determinants ; Antigens ; Biology ; Cell Line ; Clinical trials ; Drug therapy ; Effectiveness ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Epitopes, T-Lymphocyte - immunology ; Female ; Fragmentation ; Fragments ; Helper cells ; Humans ; Immune response ; Immunity ; Immunogenicity ; Immunoglobulins ; Infections ; Laboratory animals ; Lymphocytes ; Lymphocytes T ; Malaria ; Malaria vaccines ; Medicine ; Merozoite surface protein 1 ; Merozoite Surface Protein 1 - immunology ; Mice ; Molecular Sequence Data ; Parasites ; Pharmacology ; Plasmodium falciparum ; Plasmodium falciparum - immunology ; Proteins ; Rabbits ; Segments ; Sequence Homology, Amino Acid ; T cells ; Vaccines ; Vector-borne diseases</subject><ispartof>PloS one, 2011-09, Vol.6 (9), p.e24782-e24782</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Pusic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Pusic et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-ed03c01ce7732d7202374c7e826d575d96c2033edc9557b54c5845fb26f09c453</citedby><cites>FETCH-LOGICAL-c691t-ed03c01ce7732d7202374c7e826d575d96c2033edc9557b54c5845fb26f09c453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1308799702/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1308799702?pq-origsite=primo$$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/21931852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Doolan, Denise L.</contributor><creatorcontrib>Pusic, Kae M</creatorcontrib><creatorcontrib>Hashimoto, Caryn N</creatorcontrib><creatorcontrib>Lehrer, Axel</creatorcontrib><creatorcontrib>Aniya, Charmaine</creatorcontrib><creatorcontrib>Clements, David E</creatorcontrib><creatorcontrib>Hui, George S</creatorcontrib><title>T cell epitope regions of the P. falciparum MSP1-33 critically influence immune responses and in vitro efficacy of MSP1-42 vaccines</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The C-terminal 42 kDa fragments of the P. falciparum Merozoite Surface Protein 1, MSP1-42 is a leading malaria vaccine candidate. MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave in vivo evidence that T cell epitope regions of MSP1-33 provide functional help in inducing anti-MSP1-19 antibodies. Eleven truncated MSP1-33 segments were expressed in tandem with MSP1-19, and immunogenicity was evaluated in Swiss Webster mice and New Zealand White rabbits. Analyses of anti-MSP1-19 antibody responses revealed striking differences in these segments' helper function despite that they all possess T cell epitopes. Only a few fragments induced a generalized response (100%) in outbred mice. These were comparable to or surpassed the responses observed with the full length MSP1-42. In rabbits, only a subset of truncated antigens induced potent parasite growth inhibitory antibodies. Notably, two constructs were more efficacious than MSP1-42, with one containing only conserved T cell epitopes. Moreover, another T cell epitope region induced high titers of non-inhibitory antibodies and they interfered with the inhibitory activities of anti-MSP1-42 antibodies. In mice, this region also induced a skewed TH2 cellular response. This is the first demonstration that T cell epitope regions of MSP1-33 positively or negatively influenced antibody responses. Differential recognition of these regions by humans may play critical roles in vaccine induced and/or natural immunity to MSP1-42. This study provides the rational basis to re-engineer more efficacious MSP1-42 vaccines by selective inclusion and exclusion of MSP1-33 specific T cell epitopes.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibody response</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Biology</subject><subject>Cell Line</subject><subject>Clinical trials</subject><subject>Drug therapy</subject><subject>Effectiveness</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Fragmentation</subject><subject>Fragments</subject><subject>Helper cells</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Immunogenicity</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Laboratory animals</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Malaria</subject><subject>Malaria vaccines</subject><subject>Medicine</subject><subject>Merozoite surface protein 1</subject><subject>Merozoite Surface Protein 1 - immunology</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Parasites</subject><subject>Pharmacology</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - immunology</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Segments</subject><subject>Sequence Homology, Amino Acid</subject><subject>T cells</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1tv0zAUxyMEYqPwDRBYQgLx0OJLEtsvSNPEpdLQJjZ4tVznpPWUxMFOKvrMF8dps6lBe0B5cOTzO_9z80mSlwQvCOPkw63rfaOrResaWGBMUy7oo-SUSEbnOcXs8dH_SfIshFuMMyby_GlyQqOFiIyeJn9ukIGqQtDazrWAPKytawJyJeo2gK4WqNSVsa32fY2-XV-ROWPIeNtZo6tqh2xTVj00BpCt674ZBELMKEBAuimiGW1t5x2CsoweZjcI72VSirbaGNtAeJ48iUECvBjPWfLj86eb86_zi8svy_Ozi7nJJenmUGBmMDHAOaMFp5gynhoOguZFxrNC5iaWyqAwMsv4KktNJtKsXNG8xNKkGZslrw-6beWCGvsXFGFYcCl51JslywNROH2rWm9r7XfKaav2F86vlfax9AqUWIGWIGUhyzRNaSkIE4KtuABDy4LJqPVxjNav6pgUNJ3X1UR0amnsRq3dVjHCKRVDuu9GAe9-9RA6VdswDEs34PqghGSMMLlP-80_5MPFjdRax_zj4FwMawZNdZbyXAhMqIjU4gEqfgXU1sS3Vtp4P3F4P3GITAe_u7XuQ1DL6-__z17-nLJvj9gN6KrbBFf13fA-p2B6AI13IXgo73tMsBpW5a4balgVNa5KdHt1PJ97p7vdYH8BprsM0A</recordid><startdate>20110913</startdate><enddate>20110913</enddate><creator>Pusic, Kae M</creator><creator>Hashimoto, Caryn N</creator><creator>Lehrer, Axel</creator><creator>Aniya, Charmaine</creator><creator>Clements, David E</creator><creator>Hui, George S</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110913</creationdate><title>T cell epitope regions of the P. falciparum MSP1-33 critically influence immune responses and in vitro efficacy of MSP1-42 vaccines</title><author>Pusic, Kae M ; Hashimoto, Caryn N ; Lehrer, Axel ; Aniya, Charmaine ; Clements, David E ; Hui, George S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-ed03c01ce7732d7202374c7e826d575d96c2033edc9557b54c5845fb26f09c453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibody response</topic><topic>Antigenic determinants</topic><topic>Antigens</topic><topic>Biology</topic><topic>Cell Line</topic><topic>Clinical trials</topic><topic>Drug therapy</topic><topic>Effectiveness</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte - 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MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave in vivo evidence that T cell epitope regions of MSP1-33 provide functional help in inducing anti-MSP1-19 antibodies. Eleven truncated MSP1-33 segments were expressed in tandem with MSP1-19, and immunogenicity was evaluated in Swiss Webster mice and New Zealand White rabbits. Analyses of anti-MSP1-19 antibody responses revealed striking differences in these segments' helper function despite that they all possess T cell epitopes. Only a few fragments induced a generalized response (100%) in outbred mice. These were comparable to or surpassed the responses observed with the full length MSP1-42. In rabbits, only a subset of truncated antigens induced potent parasite growth inhibitory antibodies. Notably, two constructs were more efficacious than MSP1-42, with one containing only conserved T cell epitopes. Moreover, another T cell epitope region induced high titers of non-inhibitory antibodies and they interfered with the inhibitory activities of anti-MSP1-42 antibodies. In mice, this region also induced a skewed TH2 cellular response. This is the first demonstration that T cell epitope regions of MSP1-33 positively or negatively influenced antibody responses. Differential recognition of these regions by humans may play critical roles in vaccine induced and/or natural immunity to MSP1-42. This study provides the rational basis to re-engineer more efficacious MSP1-42 vaccines by selective inclusion and exclusion of MSP1-33 specific T cell epitopes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21931852</pmid><doi>10.1371/journal.pone.0024782</doi><tpages>e24782</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Antibodies Antibody response Antigenic determinants Antigens Biology Cell Line Clinical trials Drug therapy Effectiveness Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Epitopes Epitopes, T-Lymphocyte - immunology Female Fragmentation Fragments Helper cells Humans Immune response Immunity Immunogenicity Immunoglobulins Infections Laboratory animals Lymphocytes Lymphocytes T Malaria Malaria vaccines Medicine Merozoite surface protein 1 Merozoite Surface Protein 1 - immunology Mice Molecular Sequence Data Parasites Pharmacology Plasmodium falciparum Plasmodium falciparum - immunology Proteins Rabbits Segments Sequence Homology, Amino Acid T cells Vaccines Vector-borne diseases |
title | T cell epitope regions of the P. falciparum MSP1-33 critically influence immune responses and in vitro efficacy of MSP1-42 vaccines |
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