A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis
Identifieur interne : 000052 ( Main/Exploration ); précédent : 000051; suivant : 000053A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis
Auteurs : Alessandra Ricciardi [Canada] ; Kittipos Visitsunthorn [Canada] ; John P. Dalton [Canada, Royaume-Uni] ; Momar Ndao [Canada]Source :
- BMC Infectious Diseases [ 1471-2334 ] ; 2016.
Abstract
Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.
Our group has chosen
The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (
The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.
The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12879-016-1444-z
PubMed: 26945988
PubMed Central: 4779570
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A vaccine consisting of <italic>Schistosoma mansoni</italic> cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis</title><author><name sortKey="Ricciardi, Alessandra" sort="Ricciardi, Alessandra" uniqKey="Ricciardi A" first="Alessandra" last="Ricciardi">Alessandra Ricciardi</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff><wicri:noCountry code="subfield">QC Canada</wicri:noCountry></affiliation></author><author><name sortKey="Visitsunthorn, Kittipos" sort="Visitsunthorn, Kittipos" uniqKey="Visitsunthorn K" first="Kittipos" last="Visitsunthorn">Kittipos Visitsunthorn</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Institute of Parasitology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff3">School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast, Northern Ireland</nlm:aff><country>Royaume-Uni</country><placeName><region type="country">Irlande du Nord</region></placeName><wicri:cityArea>School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast</wicri:cityArea></affiliation></author><author><name sortKey="Ndao, Momar" sort="Ndao, Momar" uniqKey="Ndao M" first="Momar" last="Ndao">Momar Ndao</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff><wicri:noCountry code="subfield">QC Canada</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26945988</idno><idno type="pmc">4779570</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779570</idno><idno type="RBID">PMC:4779570</idno><idno type="doi">10.1186/s12879-016-1444-z</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000095</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000095</idno><idno type="wicri:Area/Pmc/Curation">000094</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000094</idno><idno type="wicri:Area/Pmc/Checkpoint">000047</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000047</idno><idno type="wicri:Area/Ncbi/Merge">000441</idno><idno type="wicri:Area/Ncbi/Curation">000441</idno><idno type="wicri:Area/Ncbi/Checkpoint">000441</idno><idno type="wicri:Area/Main/Merge">000052</idno><idno type="wicri:Area/Main/Curation">000052</idno><idno type="wicri:Area/Main/Exploration">000052</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A vaccine consisting of <italic>Schistosoma mansoni</italic> cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis</title><author><name sortKey="Ricciardi, Alessandra" sort="Ricciardi, Alessandra" uniqKey="Ricciardi A" first="Alessandra" last="Ricciardi">Alessandra Ricciardi</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff><wicri:noCountry code="subfield">QC Canada</wicri:noCountry></affiliation></author><author><name sortKey="Visitsunthorn, Kittipos" sort="Visitsunthorn, Kittipos" uniqKey="Visitsunthorn K" first="Kittipos" last="Visitsunthorn">Kittipos Visitsunthorn</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Institute of Parasitology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff3">School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast, Northern Ireland</nlm:aff><country>Royaume-Uni</country><placeName><region type="country">Irlande du Nord</region></placeName><wicri:cityArea>School of Biological Sciences, Medical Biology Centre (MBC) Queen’s University Belfast, Belfast</wicri:cityArea></affiliation></author><author><name sortKey="Ndao, Momar" sort="Ndao, Momar" uniqKey="Ndao M" first="Momar" last="Ndao">Momar Ndao</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Department of Microbiology & Immunology, McGill University, Montreal, QC Canada</nlm:aff><orgName type="university">Université McGill</orgName><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation><affiliation><nlm:aff id="Aff4">National Reference Center for Parasitology, Research Institute of the McGill University Health Center, Montreal, QC Canada</nlm:aff><wicri:noCountry code="subfield">QC Canada</wicri:noCountry></affiliation></author></analytic><series><title level="j">BMC Infectious Diseases</title><idno type="eISSN">1471-2334</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.</p></sec><sec><title>Method</title><p>Our group has chosen <italic>Schistosoma mansoni</italic> (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels.</p></sec><sec><title>Results</title><p>The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (<italic>P</italic> = 0.0002, <italic>P</italic> < 0.0001, <italic>P</italic> = 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls.</p></sec><sec><title>Conclusion</title><p>The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chitsulo, L" uniqKey="Chitsulo L">L Chitsulo</name></author><author><name sortKey="Engels, D" uniqKey="Engels D">D Engels</name></author><author><name sortKey="Montresor, A" uniqKey="Montresor A">A Montresor</name></author><author><name sortKey="Saviolo, L" uniqKey="Saviolo L">L Saviolo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gryseels, B" uniqKey="Gryseels B">B Gryseels</name></author><author><name sortKey="Polman, K" uniqKey="Polman K">K Polman</name></author><author><name sortKey="Clerinx, J" uniqKey="Clerinx 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Hotez</name></author><author><name sortKey="Loukas, A" uniqKey="Loukas A">A Loukas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="El Ridi, R" uniqKey="El Ridi R">R El Ridi</name></author><author><name sortKey="Tallima, H" uniqKey="Tallima H">H Tallima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tallima, H" uniqKey="Tallima H">H Tallima</name></author><author><name sortKey="Salah, M" uniqKey="Salah M">M Salah</name></author><author><name sortKey="Guirguis, Fr" uniqKey="Guirguis F">FR Guirguis</name></author><author><name sortKey="El Ridi, R" uniqKey="El Ridi R">R El Ridi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Comin, F" uniqKey="Comin F">F Comin</name></author><author><name sortKey="Speziali, E" uniqKey="Speziali E">E Speziali</name></author><author><name sortKey="Correa Oliveira, R" uniqKey="Correa Oliveira R">R Correa-Oliveira</name></author><author><name sortKey="Faria, Am" uniqKey="Faria A">AM Faria</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li></country><region><li>Irlande du Nord</li><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="Canada"><region name="Québec"><name sortKey="Ricciardi, Alessandra" sort="Ricciardi, Alessandra" uniqKey="Ricciardi A" first="Alessandra" last="Ricciardi">Alessandra Ricciardi</name></region><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name><name sortKey="Ndao, Momar" sort="Ndao, Momar" uniqKey="Ndao M" first="Momar" last="Ndao">Momar Ndao</name><name sortKey="Visitsunthorn, Kittipos" sort="Visitsunthorn, Kittipos" uniqKey="Visitsunthorn K" first="Kittipos" last="Visitsunthorn">Kittipos Visitsunthorn</name></country><country name="Royaume-Uni"><region name="Irlande du Nord"><name sortKey="Dalton, John P" sort="Dalton, John P" uniqKey="Dalton J" first="John P." last="Dalton">John P. Dalton</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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