Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice
•PGA+CWP100 is an experimental vaccine against sporotrichosis.•PGA+CWP100 induced high titers of opsonizing IgG2a.•PGA+CWP100 increased the ex vivo release of IL-12, IFN-γ and IL-4.•PGA+CWP100 induced protective antibodies against S. brasiliensis.•PGA+CWP100 was safer than CWP100 formulated with alu...
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| Veröffentlicht in: | Vaccine 2017-08, Vol.35 (34), p.4430-4436 |
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| creator | Portuondo, Deivys Leandro Batista-Duharte, Alexander Ferreira, Lucas Souza de Andrade, Cleverton Roberto Quinello, Camila Téllez-Martínez, Damiana de Aguiar Loesch, Maria Luiza Carlos, Iracilda Zeppone |
| description | •PGA+CWP100 is an experimental vaccine against sporotrichosis.•PGA+CWP100 induced high titers of opsonizing IgG2a.•PGA+CWP100 increased the ex vivo release of IL-12, IFN-γ and IL-4.•PGA+CWP100 induced protective antibodies against S. brasiliensis.•PGA+CWP100 was safer than CWP100 formulated with alum as adjuvant.•PGA adjuvant was safer than AH, alone or in formulation with the antigen.
Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine. |
| doi_str_mv | 10.1016/j.vaccine.2017.05.046 |
| format | Article |
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Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2017.05.046</identifier><identifier>PMID: 28687406</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvant ; Adjuvants ; Adjuvants, Immunologic - toxicity ; Aluminum ; Aluminum hydroxide ; Aluminum Hydroxide - immunology ; Aluminum Hydroxide - toxicity ; Animals ; Antibodies, Fungal - biosynthesis ; Antibodies, Fungal - blood ; Antibodies, Fungal - immunology ; Antigens ; Assaying ; Brazil ; Cell walls ; Cytotoxicity ; Enzyme-linked immunosorbent assay ; Formulations ; Fungal infections ; Fungal Vaccines - administration & dosage ; Fungal Vaccines - adverse effects ; Fungal Vaccines - chemistry ; Fungal Vaccines - immunology ; Fungi ; Immunity, Cellular ; Immunization ; Immunogenicity ; Immunogenicity, Vaccine ; Immunoglobulin G ; Inoculation ; Interferon ; Interleukin 12 ; Interleukin 17 ; Interleukin 4 ; Interleukin-17 - immunology ; Liver ; Lymphocytes T ; Macrophages ; Mice ; Mice, Inbred BALB C ; Montanide™ Pet Gel A ; Mycosis ; Opsonophagocytosis ; Peritoneum ; Phagocytes ; Phagocytosis ; Proteins ; Spleen ; Splenocytes ; Sporothrix - immunology ; Sporothrix brasiliensis ; Sporothrix schenckii ; Sporotrichosis ; Sporotrichosis - immunology ; Sporotrichosis - prevention & control ; Th1-Th2 Balance ; Toxicity ; Vaccination ; Vaccine ; Vaccines ; Yeasts ; Zoonoses</subject><ispartof>Vaccine, 2017-08, Vol.35 (34), p.4430-4436</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Aug 3, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-226b7e06e6548e15782cb5adace2123248a412d02c6568c4572db3ada82781253</citedby><cites>FETCH-LOGICAL-c506t-226b7e06e6548e15782cb5adace2123248a412d02c6568c4572db3ada82781253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1922874311?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004,64394,64398,72478</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28687406$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Portuondo, Deivys Leandro</creatorcontrib><creatorcontrib>Batista-Duharte, Alexander</creatorcontrib><creatorcontrib>Ferreira, Lucas Souza</creatorcontrib><creatorcontrib>de Andrade, Cleverton Roberto</creatorcontrib><creatorcontrib>Quinello, Camila</creatorcontrib><creatorcontrib>Téllez-Martínez, Damiana</creatorcontrib><creatorcontrib>de Aguiar Loesch, Maria Luiza</creatorcontrib><creatorcontrib>Carlos, Iracilda Zeppone</creatorcontrib><title>Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•PGA+CWP100 is an experimental vaccine against sporotrichosis.•PGA+CWP100 induced high titers of opsonizing IgG2a.•PGA+CWP100 increased the ex vivo release of IL-12, IFN-γ and IL-4.•PGA+CWP100 induced protective antibodies against S. brasiliensis.•PGA+CWP100 was safer than CWP100 formulated with alum as adjuvant.•PGA adjuvant was safer than AH, alone or in formulation with the antigen.
Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine.</description><subject>Adjuvant</subject><subject>Adjuvants</subject><subject>Adjuvants, Immunologic - toxicity</subject><subject>Aluminum</subject><subject>Aluminum hydroxide</subject><subject>Aluminum Hydroxide - immunology</subject><subject>Aluminum Hydroxide - toxicity</subject><subject>Animals</subject><subject>Antibodies, Fungal - biosynthesis</subject><subject>Antibodies, Fungal - blood</subject><subject>Antibodies, Fungal - immunology</subject><subject>Antigens</subject><subject>Assaying</subject><subject>Brazil</subject><subject>Cell walls</subject><subject>Cytotoxicity</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Formulations</subject><subject>Fungal infections</subject><subject>Fungal Vaccines - administration & dosage</subject><subject>Fungal Vaccines - adverse effects</subject><subject>Fungal Vaccines - chemistry</subject><subject>Fungal Vaccines - immunology</subject><subject>Fungi</subject><subject>Immunity, Cellular</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunogenicity, Vaccine</subject><subject>Immunoglobulin G</subject><subject>Inoculation</subject><subject>Interferon</subject><subject>Interleukin 12</subject><subject>Interleukin 17</subject><subject>Interleukin 4</subject><subject>Interleukin-17 - immunology</subject><subject>Liver</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Montanide™ Pet Gel A</subject><subject>Mycosis</subject><subject>Opsonophagocytosis</subject><subject>Peritoneum</subject><subject>Phagocytes</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Spleen</subject><subject>Splenocytes</subject><subject>Sporothrix - immunology</subject><subject>Sporothrix brasiliensis</subject><subject>Sporothrix schenckii</subject><subject>Sporotrichosis</subject><subject>Sporotrichosis - immunology</subject><subject>Sporotrichosis - prevention & control</subject><subject>Th1-Th2 Balance</subject><subject>Toxicity</subject><subject>Vaccination</subject><subject>Vaccine</subject><subject>Vaccines</subject><subject>Yeasts</subject><subject>Zoonoses</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFUc2O0zAQjhCILQuPABqJc4LtxE72hFYVLEiLQAIkbpZrT7ZTGrvYTtneeRLEk_EkeNXCldMcvj_N91XVU84azrh6sWn2xlry2AjG-4bJhnXqXrXgQ9_WQvLhfrVgQnV1x9mXs-pRShvGmGz5xcPqTAxq6DumFtWvZZh2JppMewQcR7LGHsB4BznckqV8gDBC_h7gFAe2gORMxgTmxpBPGT7uQgx5HekWkl2jt1-JYE7kbwAprzHCu-Cz8eTw94-f8AEzXOEWLiFEMNt5Ij9PsD64WCIdgnGbeW98TkAeJrL4uHowmm3CJ6d7Xn1-_erT8k19_f7q7fLyuraSqVwLoVY9MoVKdgNy2Q_CrqRxxqLgohXdYDouHBNWSTXYTvbCrdqCD6IfuJDtefX86LuL4duMKetNmKMvkZpfCFEqazkvLHlk2RhSijjqXaTJxIPmTN9tozf6VJa-20Yzqcs2Rffs5D6vJnT_VH_HKISXRwKWH_eEUSdLpU10FNFm7QL9J-IPMwSmOw</recordid><startdate>20170803</startdate><enddate>20170803</enddate><creator>Portuondo, 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efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice</title><author>Portuondo, Deivys Leandro ; Batista-Duharte, Alexander ; Ferreira, Lucas Souza ; de Andrade, Cleverton Roberto ; Quinello, Camila ; Téllez-Martínez, Damiana ; de Aguiar Loesch, Maria Luiza ; Carlos, Iracilda Zeppone</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-226b7e06e6548e15782cb5adace2123248a412d02c6568c4572db3ada82781253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adjuvant</topic><topic>Adjuvants</topic><topic>Adjuvants, Immunologic - toxicity</topic><topic>Aluminum</topic><topic>Aluminum hydroxide</topic><topic>Aluminum Hydroxide - immunology</topic><topic>Aluminum Hydroxide - toxicity</topic><topic>Animals</topic><topic>Antibodies, Fungal - biosynthesis</topic><topic>Antibodies, Fungal - 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A</topic><topic>Mycosis</topic><topic>Opsonophagocytosis</topic><topic>Peritoneum</topic><topic>Phagocytes</topic><topic>Phagocytosis</topic><topic>Proteins</topic><topic>Spleen</topic><topic>Splenocytes</topic><topic>Sporothrix - immunology</topic><topic>Sporothrix brasiliensis</topic><topic>Sporothrix schenckii</topic><topic>Sporotrichosis</topic><topic>Sporotrichosis - immunology</topic><topic>Sporotrichosis - prevention & control</topic><topic>Th1-Th2 Balance</topic><topic>Toxicity</topic><topic>Vaccination</topic><topic>Vaccine</topic><topic>Vaccines</topic><topic>Yeasts</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Portuondo, Deivys Leandro</creatorcontrib><creatorcontrib>Batista-Duharte, Alexander</creatorcontrib><creatorcontrib>Ferreira, Lucas Souza</creatorcontrib><creatorcontrib>de Andrade, Cleverton Roberto</creatorcontrib><creatorcontrib>Quinello, Camila</creatorcontrib><creatorcontrib>Téllez-Martínez, 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mice</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2017-08-03</date><risdate>2017</risdate><volume>35</volume><issue>34</issue><spage>4430</spage><epage>4436</epage><pages>4430-4436</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•PGA+CWP100 is an experimental vaccine against sporotrichosis.•PGA+CWP100 induced high titers of opsonizing IgG2a.•PGA+CWP100 increased the ex vivo release of IL-12, IFN-γ and IL-4.•PGA+CWP100 induced protective antibodies against S. brasiliensis.•PGA+CWP100 was safer than CWP100 formulated with alum as adjuvant.•PGA adjuvant was safer than AH, alone or in formulation with the antigen.
Sporotrichosis is an important zoonosis in Brazil and the most frequent subcutaneous mycosis in Latin America, caused by different Sporothrix species. Currently, there is no effective vaccine available to prevent this disease. In this study, the efficacy and toxicity of the adjuvant Montanide™ Pet Gel A (PGA) formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and compared with that of aluminum hydroxide (AH). Balb/c mice received two subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the phagocytic index, as well as the ex vivo release of IFN-γ, IL-4, and IL-17 by splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of the vaccine formulations was evaluated in vitro and by histopathological analysis of the inoculation site. Both adjuvanted vaccine formulations increased anti-ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in response to PGA+CWP100, probably contributing to the increase in S. schenckii yeast phagocytosis by macrophages in the opsonophagocytosis assay when using serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro, caused less local toxicity and led to a similar reduction in fungal load in the liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared with AH+CWP100. These results suggest that PGA may be an effective and safe adjuvant for a future sporotrichosis vaccine.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28687406</pmid><doi>10.1016/j.vaccine.2017.05.046</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0264-410X |
| ispartof | Vaccine, 2017-08, Vol.35 (34), p.4430-4436 |
| issn | 0264-410X 1873-2518 |
| language | eng |
| recordid | cdi_proquest_journals_1922874311 |
| source | MEDLINE; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Adjuvant Adjuvants Adjuvants, Immunologic - toxicity Aluminum Aluminum hydroxide Aluminum Hydroxide - immunology Aluminum Hydroxide - toxicity Animals Antibodies, Fungal - biosynthesis Antibodies, Fungal - blood Antibodies, Fungal - immunology Antigens Assaying Brazil Cell walls Cytotoxicity Enzyme-linked immunosorbent assay Formulations Fungal infections Fungal Vaccines - administration & dosage Fungal Vaccines - adverse effects Fungal Vaccines - chemistry Fungal Vaccines - immunology Fungi Immunity, Cellular Immunization Immunogenicity Immunogenicity, Vaccine Immunoglobulin G Inoculation Interferon Interleukin 12 Interleukin 17 Interleukin 4 Interleukin-17 - immunology Liver Lymphocytes T Macrophages Mice Mice, Inbred BALB C Montanide™ Pet Gel A Mycosis Opsonophagocytosis Peritoneum Phagocytes Phagocytosis Proteins Spleen Splenocytes Sporothrix - immunology Sporothrix brasiliensis Sporothrix schenckii Sporotrichosis Sporotrichosis - immunology Sporotrichosis - prevention & control Th1-Th2 Balance Toxicity Vaccination Vaccine Vaccines Yeasts Zoonoses |
| title | Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-02T14%3A54%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparative%20efficacy%20and%20toxicity%20of%20two%20vaccine%20candidates%20against%20Sporothrix%20schenckii%20using%20either%20Montanide%E2%84%A2%20Pet%20Gel%20A%20or%20aluminum%20hydroxide%20adjuvants%20in%20mice&rft.jtitle=Vaccine&rft.au=Portuondo,%20Deivys%20Leandro&rft.date=2017-08-03&rft.volume=35&rft.issue=34&rft.spage=4430&rft.epage=4436&rft.pages=4430-4436&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2017.05.046&rft_dat=%3Cproquest_cross%3E1922874311%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1922874311&rft_id=info:pmid/28687406&rft_els_id=S0264410X17306825&rfr_iscdi=true |