Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model
Identifieur interne : 001234 ( Main/Curation ); précédent : 001233; suivant : 001235Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model
Auteurs : Luther A. Bartelt [États-Unis] ; David T. Bolick [États-Unis] ; Glynis L. Kolling [États-Unis] ; James K. Roche [États-Unis] ; Edna I. Zaenker [États-Unis] ; Ana M. Lara [États-Unis] ; Francisco Jose Noronha [États-Unis] ; Carrie A. Cowardin [États-Unis] ; John H. Moore [États-Unis] ; Jerrold R. Turner [États-Unis] ; Cirle A. Warren [États-Unis] ; Gregory A. Buck [États-Unis] ; Richard L. Guerrant [États-Unis]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Abstract
Url:
DOI: 10.1371/journal.pntd.0004820
PubMed: 27467505
PubMed Central: 4965189
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PMC:4965189Le document en format XML
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Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model</title>
<author><name sortKey="Bartelt, Luther A" sort="Bartelt, Luther A" uniqKey="Bartelt L" first="Luther A." last="Bartelt">Luther A. Bartelt</name>
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</nlm:aff>
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<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
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<author><name sortKey="Bolick, David T" sort="Bolick, David T" uniqKey="Bolick D" first="David T." last="Bolick">David T. Bolick</name>
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</nlm:aff>
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</placeName>
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<author><name sortKey="Kolling, Glynis L" sort="Kolling, Glynis L" uniqKey="Kolling G" first="Glynis L." last="Kolling">Glynis L. Kolling</name>
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</nlm:aff>
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</placeName>
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<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Departments of Pathology and Medicine—Gastroenterology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Cryptosporidium</italic>
Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model</title>
<author><name sortKey="Bartelt, Luther A" sort="Bartelt, Luther A" uniqKey="Bartelt L" first="Luther A." last="Bartelt">Luther A. Bartelt</name>
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</nlm:aff>
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<wicri:regionArea>Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
</affiliation>
</author>
<author><name sortKey="Bolick, David T" sort="Bolick, David T" uniqKey="Bolick D" first="David T." last="Bolick">David T. Bolick</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kolling, Glynis L" sort="Kolling, Glynis L" uniqKey="Kolling G" first="Glynis L." last="Kolling">Glynis L. Kolling</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
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<author><name sortKey="Roche, James K" sort="Roche, James K" uniqKey="Roche J" first="James K." last="Roche">James K. Roche</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zaenker, Edna I" sort="Zaenker, Edna I" uniqKey="Zaenker E" first="Edna I." last="Zaenker">Edna I. Zaenker</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lara, Ana M" sort="Lara, Ana M" uniqKey="Lara A" first="Ana M." last="Lara">Ana M. Lara</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Molecular Biology and Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Molecular Biology and Genetics, Virginia Commonwealth University, Richmond, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Noronha, Francisco Jose" sort="Noronha, Francisco Jose" uniqKey="Noronha F" first="Francisco Jose" last="Noronha">Francisco Jose Noronha</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cowardin, Carrie A" sort="Cowardin, Carrie A" uniqKey="Cowardin C" first="Carrie A." last="Cowardin">Carrie A. Cowardin</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Moore, John H" sort="Moore, John H" uniqKey="Moore J" first="John H." last="Moore">John H. Moore</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Turner, Jerrold R" sort="Turner, Jerrold R" uniqKey="Turner J" first="Jerrold R." last="Turner">Jerrold R. Turner</name>
<affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, The University of Chicago, Chicago, Illinois</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Departments of Pathology and Medicine—Gastroenterology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Pathology and Medicine—Gastroenterology, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Warren, Cirle A" sort="Warren, Cirle A" uniqKey="Warren C" first="Cirle A." last="Warren">Cirle A. Warren</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Buck, Gregory A" sort="Buck, Gregory A" uniqKey="Buck G" first="Gregory A." last="Buck">Gregory A. Buck</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Molecular Biology and Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Molecular Biology and Genetics, Virginia Commonwealth University, Richmond, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guerrant, Richard L" sort="Guerrant, Richard L" uniqKey="Guerrant R" first="Richard L." last="Guerrant">Richard L. Guerrant</name>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia</wicri:regionArea>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p><italic>Cryptosporidium</italic>
is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of <italic>C</italic>
. <italic>parvum</italic>
oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to <italic>C</italic>
. <italic>parvum</italic>
challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to <italic>Cryptosporidium</italic>
, priming with <italic>C</italic>
. <italic>parvum</italic>
(10<sup>6</sup>
oocysts) provides robust protective immunity against re-challenge despite ongoing PM. <italic>C</italic>
. <italic>parvum</italic>
priming restores mucosal Th1-type effectors (CD3<sup>+</sup>
CD8<sup>+</sup>
CD103<sup>+</sup>
T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with <italic>Cryptosporidium</italic>
antigens expressed in the <italic>S</italic>
. Typhi vector 908<italic>htr</italic>
, however, do not enhance Th1-type responses to <italic>C</italic>
. <italic>parvum</italic>
challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated <italic>S</italic>
. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate <italic>C</italic>
. <italic>parvum</italic>
severity during PM, but neither as effectively as viable <italic>C</italic>
. <italic>parvum</italic>
priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to <italic>C</italic>
. <italic>parvum</italic>
, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically <italic>C</italic>
. <italic>parvum</italic>
priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of <italic>Cryptosporidium</italic>
immunity and future vaccine strategies in malnourished children.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Black, Re" uniqKey="Black R">RE Black</name>
</author>
<author><name sortKey="Victora, Cg" uniqKey="Victora C">CG Victora</name>
</author>
<author><name sortKey="Walker, Sp" uniqKey="Walker S">SP Walker</name>
</author>
<author><name sortKey="Bhutta, Za" uniqKey="Bhutta Z">ZA Bhutta</name>
</author>
<author><name sortKey="Christian, P" uniqKey="Christian P">P Christian</name>
</author>
<author><name sortKey="De Onis, M" uniqKey="De Onis M">M de Onis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rytter, Mjh" uniqKey="Rytter M">MJH Rytter</name>
</author>
<author><name sortKey="Kolte, L" uniqKey="Kolte L">L Kolte</name>
</author>
<author><name sortKey="Briend, A" uniqKey="Briend A">A Briend</name>
</author>
<author><name sortKey="Friis, H" uniqKey="Friis H">H Friis</name>
</author>
<author><name sortKey="Christensen, Vb" uniqKey="Christensen V">VB Christensen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Haque, R" uniqKey="Haque R">R Haque</name>
</author>
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