IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice
The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under...
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| Veröffentlicht in: | PloS one 2014-10, Vol.9 (10), p.e111020-e111020 |
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| creator | Schwenk, Robert DeBot, Margot Porter, Michael Nikki, Jennifer Rein, Lisa Spaccapelo, Roberta Crisanti, Andrea Wightman, Paul D Ockenhouse, Christian F Dutta, Sheetij |
| description | The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans. |
| doi_str_mv | 10.1371/journal.pone.0111020 |
| format | Article |
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Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0111020</identifier><identifier>PMID: 25343487</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alum ; Aluminum sulfate ; Animals ; Antibodies ; Antibodies, Monoclonal - immunology ; Antibodies, Protozoan - immunology ; Antibody response ; Antigens ; Antigens, Protozoan - immunology ; B cells ; B-Lymphocytes - immunology ; B7-2 Antigen - metabolism ; Biology and Life Sciences ; Circumsporozoite protein ; Cyclic GMP ; D antigen ; Dendritic cells ; Dose-Response Relationship, Immunologic ; Drug delivery systems ; E coli ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; Formulations ; Genetic engineering ; House mouse ; Immune system ; Immunity ; Immunogenicity ; Immunoglobulin G ; Immunoglobulin G - immunology ; Immunoglobulins ; Infections ; Ligands ; Lipid A ; Lipids ; Lymphocytes T ; Malaria ; Malaria Vaccines - immunology ; Malaria, Falciparum - immunology ; Malaria, Falciparum - prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Oncorhynchus mykiss ; Parasites ; Parasitic diseases ; Pattern recognition ; Plasmodium ; Plasmodium falciparum ; Plasmodium falciparum - immunology ; Proteins ; Protozoan Proteins - immunology ; Signal transduction ; Sporozoites - immunology ; T cells ; TLR4 protein ; TLR7 protein ; Toll-like receptors ; Toll-Like Receptors - agonists ; Transgenic mice ; Tropical diseases ; Vaccination ; Vaccines ; Vector-borne diseases</subject><ispartof>PloS one, 2014-10, Vol.9 (10), p.e111020-e111020</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5f8ec7ffce38f8f9edf0fa6ac54e711dff73c441dcaad881943f96e27a24bb843</citedby><cites>FETCH-LOGICAL-c692t-5f8ec7ffce38f8f9edf0fa6ac54e711dff73c441dcaad881943f96e27a24bb843</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/PMC4208815/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208815/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25343487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tetteh, Kevin KA</contributor><creatorcontrib>Schwenk, Robert</creatorcontrib><creatorcontrib>DeBot, Margot</creatorcontrib><creatorcontrib>Porter, Michael</creatorcontrib><creatorcontrib>Nikki, Jennifer</creatorcontrib><creatorcontrib>Rein, Lisa</creatorcontrib><creatorcontrib>Spaccapelo, Roberta</creatorcontrib><creatorcontrib>Crisanti, Andrea</creatorcontrib><creatorcontrib>Wightman, Paul D</creatorcontrib><creatorcontrib>Ockenhouse, Christian F</creatorcontrib><creatorcontrib>Dutta, Sheetij</creatorcontrib><title>IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.</description><subject>Alum</subject><subject>Aluminum sulfate</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Protozoan - immunology</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Antigens, Protozoan - immunology</subject><subject>B cells</subject><subject>B-Lymphocytes - immunology</subject><subject>B7-2 Antigen - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Circumsporozoite protein</subject><subject>Cyclic GMP</subject><subject>D antigen</subject><subject>Dendritic cells</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Drug delivery systems</subject><subject>E coli</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Escherichia coli</subject><subject>Formulations</subject><subject>Genetic engineering</subject><subject>House mouse</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Ligands</subject><subject>Lipid A</subject><subject>Lipids</subject><subject>Lymphocytes T</subject><subject>Malaria</subject><subject>Malaria Vaccines - immunology</subject><subject>Malaria, Falciparum - immunology</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Oncorhynchus mykiss</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Pattern recognition</subject><subject>Plasmodium</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - immunology</subject><subject>Proteins</subject><subject>Protozoan Proteins - immunology</subject><subject>Signal transduction</subject><subject>Sporozoites - immunology</subject><subject>T cells</subject><subject>TLR4 protein</subject><subject>TLR7 protein</subject><subject>Toll-like receptors</subject><subject>Toll-Like Receptors - agonists</subject><subject>Transgenic mice</subject><subject>Tropical diseases</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11vVCEQhk-MxtbqPzBKYmL0Ylc4cL5uTJqN1k2atLHqLZnlDGdpWFiBUz9-iz9Wtt1uuqYXhgvI8Mw78MIUxXNGp4w37N2lH4MDO117h1PKGKMlfVAcso6Xk7qk_OGd9UHxJMZLSive1vXj4qCsuOCibQ6LP_PhpCTgkln43mAkMIBxMREgyhpnFFgyBOiRnFuIq8yMK6LBKrOGkJezi3NyBUoZh9cqAzoCMXplICH5YdKSrINPqJLxbieeAriYUaNIXPvgf3uTabUEa9ENSIwjK6PwafEol4r4bDsfFV8_fvgy-zQ5PTuZz45PJ6ruyjSpdIuq0Vohb3WrO-w11VCDqgQ2jPVaN1wJwXoF0Lct6wTXXY1lA6VYLFrBj4qXN7pr66PcGhslq_NoWF3VmZjfEL2HS7kOZgXhl_Rg5HXAh0FCSEZZlNDWXcW4rjldiGYBreZK61JXZc-rkmPWer-tNi5W2Ct02Q67J7q_48xSDv5KipLm01dZ4M1WIPjvI8YkVyYqtBYc-vH63BmjlaAZffUPev_tttQA-QLGaZ_rqo2oPBasyQ51vM3U9B4qjx7zY-VfqE2O7yW83UvITMKfaYAxRjm_-Pz_7Nm3ffb1HXaJYNMyejtuvljcB8UNqIKPMaDemcyo3DTRrRty00Ry20Q57cXdB9ol3XYN_wsFGxsS</recordid><startdate>20141024</startdate><enddate>20141024</enddate><creator>Schwenk, Robert</creator><creator>DeBot, Margot</creator><creator>Porter, Michael</creator><creator>Nikki, Jennifer</creator><creator>Rein, Lisa</creator><creator>Spaccapelo, Roberta</creator><creator>Crisanti, Andrea</creator><creator>Wightman, Paul D</creator><creator>Ockenhouse, Christian F</creator><creator>Dutta, Sheetij</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>20141024</creationdate><title>IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice</title><author>Schwenk, Robert ; DeBot, Margot ; Porter, Michael ; Nikki, Jennifer ; Rein, Lisa ; Spaccapelo, Roberta ; Crisanti, Andrea ; Wightman, Paul D ; Ockenhouse, Christian F ; Dutta, Sheetij</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5f8ec7ffce38f8f9edf0fa6ac54e711dff73c441dcaad881943f96e27a24bb843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alum</topic><topic>Aluminum sulfate</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - 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immunology</topic><topic>Malaria, Falciparum - immunology</topic><topic>Malaria, Falciparum - prevention & control</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Oncorhynchus mykiss</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Pattern recognition</topic><topic>Plasmodium</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - immunology</topic><topic>Proteins</topic><topic>Protozoan Proteins - immunology</topic><topic>Signal transduction</topic><topic>Sporozoites - immunology</topic><topic>T cells</topic><topic>TLR4 protein</topic><topic>TLR7 protein</topic><topic>Toll-like receptors</topic><topic>Toll-Like Receptors - agonists</topic><topic>Transgenic mice</topic><topic>Tropical diseases</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwenk, Robert</creatorcontrib><creatorcontrib>DeBot, Margot</creatorcontrib><creatorcontrib>Porter, Michael</creatorcontrib><creatorcontrib>Nikki, Jennifer</creatorcontrib><creatorcontrib>Rein, Lisa</creatorcontrib><creatorcontrib>Spaccapelo, Roberta</creatorcontrib><creatorcontrib>Crisanti, Andrea</creatorcontrib><creatorcontrib>Wightman, Paul D</creatorcontrib><creatorcontrib>Ockenhouse, Christian F</creatorcontrib><creatorcontrib>Dutta, Sheetij</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schwenk, Robert</au><au>DeBot, Margot</au><au>Porter, Michael</au><au>Nikki, Jennifer</au><au>Rein, Lisa</au><au>Spaccapelo, Roberta</au><au>Crisanti, Andrea</au><au>Wightman, Paul D</au><au>Ockenhouse, Christian F</au><au>Dutta, Sheetij</au><au>Tetteh, Kevin KA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-10-24</date><risdate>2014</risdate><volume>9</volume><issue>10</issue><spage>e111020</spage><epage>e111020</epage><pages>e111020-e111020</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25343487</pmid><doi>10.1371/journal.pone.0111020</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-10, Vol.9 (10), p.e111020-e111020 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1616171656 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alum Aluminum sulfate Animals Antibodies Antibodies, Monoclonal - immunology Antibodies, Protozoan - immunology Antibody response Antigens Antigens, Protozoan - immunology B cells B-Lymphocytes - immunology B7-2 Antigen - metabolism Biology and Life Sciences Circumsporozoite protein Cyclic GMP D antigen Dendritic cells Dose-Response Relationship, Immunologic Drug delivery systems E coli Enzyme-Linked Immunosorbent Assay Escherichia coli Formulations Genetic engineering House mouse Immune system Immunity Immunogenicity Immunoglobulin G Immunoglobulin G - immunology Immunoglobulins Infections Ligands Lipid A Lipids Lymphocytes T Malaria Malaria Vaccines - immunology Malaria, Falciparum - immunology Malaria, Falciparum - prevention & control Mice Mice, Inbred BALB C Mice, Inbred C57BL Oncorhynchus mykiss Parasites Parasitic diseases Pattern recognition Plasmodium Plasmodium falciparum Plasmodium falciparum - immunology Proteins Protozoan Proteins - immunology Signal transduction Sporozoites - immunology T cells TLR4 protein TLR7 protein Toll-like receptors Toll-Like Receptors - agonists Transgenic mice Tropical diseases Vaccination Vaccines Vector-borne diseases |
| title | IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice |
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