The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques—implications for recombinant vaccine design
Identifieur interne : 002674 ( Main/Exploration ); précédent : 002673; suivant : 002675The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques—implications for recombinant vaccine design
Auteurs : Philip A. Mudd [États-Unis] ; Shari M. Piaskowski [États-Unis] ; Patricia C. Costa Neves [Brésil] ; Richard Rudersdorf [États-Unis] ; Holly L. Kolar [États-Unis] ; Christopher M. Eernisse [États-Unis] ; Kim L. Weisgrau [États-Unis] ; Marlon G. Veloso De Santana [Brésil] ; Nancy A. Wilson [États-Unis] ; Myrna C. Bonaldo [Brésil] ; Ricardo Galler [Brésil] ; Eva G. Rakasz [États-Unis] ; David I. Watkins [États-Unis]Source :
- Immunogenetics [ 0093-7711 ] ; 2010-09-01.
Descripteurs français
- Wicri :
- topic : Vaccin.
English descriptors
Abstract
Abstract: The yellow fever vaccine 17D (YF17D) is one of the most effective vaccines. Its wide use and favorable safety profile make it a prime candidate for recombinant vaccines. It is believed that neutralizing antibodies account for a large measure of the protection afforded to YF17D-vaccinated individuals, however cytotoxic T lymphocyte (CTL) responses have been described in the setting of YF17D vaccination. YF17D is an ssRNA flavivirus that is translated as a full-length polyprotein, several domains of which pass into the lumen of the endoplasmic reticulum (ER). The processing and presentation machinery for MHC class I-restricted CTL responses favor cytoplasmic peptides that are transported into the ER by the transporter associated with antigen presentation proteins. In order to inform recombinant vaccine design, we sought to determine if YF17D-induced CTL responses preferentially targeted viral domains that remain within the cytoplasm. We performed whole YF17D proteome mapping of CTL responses in six Indian rhesus macaques vaccinated with YF17D using overlapping YF17D peptides. We found that the ER luminal E protein was the most immunogenic viral protein followed closely by the cytoplasmic NS3 and NS5 proteins. These results suggest that antigen processing and presentation in this model system is not preferentially affected by the subcellular location of the viral proteins that are the source of CTL epitopes. The data also suggest potential immunogenic regions of YF17D that could serve as the focus of recombinant T cell vaccine development.
Url:
DOI: 10.1007/s00251-010-0461-0
Affiliations:
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Rakasz</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><wicri:noRegion>WI</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI</wicri:regionArea><wicri:noRegion>WI</wicri:noRegion></affiliation></author><author><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><wicri:noRegion>WI</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI</wicri:regionArea><wicri:noRegion>WI</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Immunogenetics</title><title level="j" type="abbrev">Immunogenetics</title><idno type="ISSN">0093-7711</idno><idno type="eISSN">1432-1211</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2010-09-01">2010-09-01</date><biblScope unit="volume">62</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="593">593</biblScope><biblScope unit="page" to="600">600</biblScope></imprint><idno type="ISSN">0093-7711</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0093-7711</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cytotoxic T lymphocyte</term><term>Indian rhesus macaque</term><term>Vaccine</term><term>Yellow fever 17D</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The yellow fever vaccine 17D (YF17D) is one of the most effective vaccines. Its wide use and favorable safety profile make it a prime candidate for recombinant vaccines. It is believed that neutralizing antibodies account for a large measure of the protection afforded to YF17D-vaccinated individuals, however cytotoxic T lymphocyte (CTL) responses have been described in the setting of YF17D vaccination. YF17D is an ssRNA flavivirus that is translated as a full-length polyprotein, several domains of which pass into the lumen of the endoplasmic reticulum (ER). The processing and presentation machinery for MHC class I-restricted CTL responses favor cytoplasmic peptides that are transported into the ER by the transporter associated with antigen presentation proteins. In order to inform recombinant vaccine design, we sought to determine if YF17D-induced CTL responses preferentially targeted viral domains that remain within the cytoplasm. We performed whole YF17D proteome mapping of CTL responses in six Indian rhesus macaques vaccinated with YF17D using overlapping YF17D peptides. We found that the ER luminal E protein was the most immunogenic viral protein followed closely by the cytoplasmic NS3 and NS5 proteins. These results suggest that antigen processing and presentation in this model system is not preferentially affected by the subcellular location of the viral proteins that are the source of CTL epitopes. The data also suggest potential immunogenic regions of YF17D that could serve as the focus of recombinant T cell vaccine development.</div></front></TEI><affiliations><list><country><li>Brésil</li><li>États-Unis</li></country><region><li>État de Rio de Janeiro</li></region><settlement><li>Rio de Janeiro</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Mudd, Philip A" sort="Mudd, Philip A" uniqKey="Mudd P" first="Philip A." last="Mudd">Philip A. Mudd</name></noRegion><name sortKey="Eernisse, Christopher M" sort="Eernisse, Christopher M" uniqKey="Eernisse C" first="Christopher M." last="Eernisse">Christopher M. Eernisse</name><name sortKey="Kolar, Holly L" sort="Kolar, Holly L" uniqKey="Kolar H" first="Holly L." last="Kolar">Holly L. Kolar</name><name sortKey="Piaskowski, Shari M" sort="Piaskowski, Shari M" uniqKey="Piaskowski S" first="Shari M." last="Piaskowski">Shari M. Piaskowski</name><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name><name sortKey="Rudersdorf, Richard" sort="Rudersdorf, Richard" uniqKey="Rudersdorf R" first="Richard" last="Rudersdorf">Richard Rudersdorf</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Weisgrau, Kim L" sort="Weisgrau, Kim L" uniqKey="Weisgrau K" first="Kim L." last="Weisgrau">Kim L. Weisgrau</name><name sortKey="Wilson, Nancy A" sort="Wilson, Nancy A" uniqKey="Wilson N" first="Nancy A." last="Wilson">Nancy A. Wilson</name></country><country name="Brésil"><region name="État de Rio de Janeiro"><name sortKey="Neves, Patricia C Costa" sort="Neves, Patricia C Costa" uniqKey="Neves P" first="Patricia C. Costa" last="Neves">Patricia C. Costa Neves</name></region><name sortKey="Bonaldo, Myrna C" sort="Bonaldo, Myrna C" uniqKey="Bonaldo M" first="Myrna C." last="Bonaldo">Myrna C. Bonaldo</name><name sortKey="De Santana, Marlon G Veloso" sort="De Santana, Marlon G Veloso" uniqKey="De Santana M" first="Marlon G. Veloso" last="De Santana">Marlon G. Veloso De Santana</name><name sortKey="Galler, Ricardo" sort="Galler, Ricardo" uniqKey="Galler R" first="Ricardo" last="Galler">Ricardo Galler</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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