Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine
Identifieur interne : 001056 ( Main/Exploration ); précédent : 001055; suivant : 001057Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine
Auteurs : Carolien E. Van De Sandt [Pays-Bas] ; Joost H. C. M. Kreijtz [Pays-Bas] ; Martina M. Geelhoed-Mieras [Pays-Bas] ; Stella E. Vogelzang-Van Trierum [Pays-Bas] ; Nella J. Nieuwkoop [Pays-Bas] ; David A. M. C. Van De Vijver [Pays-Bas] ; Ron A. M. Fouchier [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Bror Morein [Suède] ; Guus F. Rimmelzwaan [Pays-Bas]Source :
- Vaccine [ 0264-410X ] ; 2014.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Vaccination, Vaccin.
English descriptors
- KwdEn :
Abstract
Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8+ T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses.
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine</title><author><name sortKey="Van De Sandt, Carolien E" sort="Van De Sandt, Carolien E" uniqKey="Van De Sandt C" first="Carolien E." last="Van De Sandt">Carolien E. Van De Sandt</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Kreijtz, Joost H C M" sort="Kreijtz, Joost H C M" uniqKey="Kreijtz J" first="Joost H. C. M." last="Kreijtz">Joost H. C. M. Kreijtz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Geelhoed Mieras, Martina M" sort="Geelhoed Mieras, Martina M" uniqKey="Geelhoed Mieras M" first="Martina M." last="Geelhoed-Mieras">Martina M. 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Vogelzang-Van Trierum</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Nieuwkoop, Nella J" sort="Nieuwkoop, Nella J" uniqKey="Nieuwkoop N" first="Nella J." last="Nieuwkoop">Nella J. Nieuwkoop</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van De Vijver, David A M C" sort="Van De Vijver, David A M C" uniqKey="Van De Vijver D" first="David A. M. C." last="Van De Vijver">David A. M. C. Van De Vijver</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>ViroClinics Biosciences BV, Marconistraat 16</s1><s2>3029 AK Rotterdam</s2><s3>NLD</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3029 AK Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Morein, Bror" sort="Morein, Bror" uniqKey="Morein B" first="Bror" last="Morein">Bror Morein</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Infectious Diseases Department of Medical Sciences, Uppsala University, MoreinX, Dag Hammarskjoldsvag 34 A</s1><s2>751 83 Uppsala</s2><s3>SWE</s3><sZ>9 aut.</sZ></inist:fA14><country>Suède</country><wicri:noRegion>751 83 Uppsala</wicri:noRegion><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>ViroClinics Biosciences BV, Marconistraat 16</s1><s2>3029 AK Rotterdam</s2><s3>NLD</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3029 AK Rotterdam</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0250693</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0250693 INIST</idno><idno type="RBID">Pascal:14-0250693</idno><idno type="wicri:Area/PascalFrancis/Corpus">000028</idno><idno type="wicri:Area/PascalFrancis/Curation">001D91</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000064</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000064</idno><idno type="wicri:doubleKey">0264-410X:2014:Van De Sandt C:novel:g:dt</idno><idno type="wicri:Area/Main/Merge">001065</idno><idno type="wicri:Area/Main/Curation">001056</idno><idno type="wicri:Area/Main/Exploration">001056</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine</title><author><name sortKey="Van De Sandt, Carolien E" sort="Van De Sandt, Carolien E" uniqKey="Van De Sandt C" first="Carolien E." last="Van De Sandt">Carolien E. Van De Sandt</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Kreijtz, Joost H C M" sort="Kreijtz, Joost H C M" uniqKey="Kreijtz J" first="Joost H. C. M." last="Kreijtz">Joost H. C. M. Kreijtz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Geelhoed Mieras, Martina M" sort="Geelhoed Mieras, Martina M" uniqKey="Geelhoed Mieras M" first="Martina M." last="Geelhoed-Mieras">Martina M. Geelhoed-Mieras</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Vogelzang Van Trierum, Stella E" sort="Vogelzang Van Trierum, Stella E" uniqKey="Vogelzang Van Trierum S" first="Stella E." last="Vogelzang-Van Trierum">Stella E. Vogelzang-Van Trierum</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Nieuwkoop, Nella J" sort="Nieuwkoop, Nella J" uniqKey="Nieuwkoop N" first="Nella J." last="Nieuwkoop">Nella J. Nieuwkoop</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van De Vijver, David A M C" sort="Van De Vijver, David A M C" uniqKey="Van De Vijver D" first="David A. M. C." last="Van De Vijver">David A. M. C. Van De Vijver</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>ViroClinics Biosciences BV, Marconistraat 16</s1><s2>3029 AK Rotterdam</s2><s3>NLD</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3029 AK Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Morein, Bror" sort="Morein, Bror" uniqKey="Morein B" first="Bror" last="Morein">Bror Morein</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Infectious Diseases Department of Medical Sciences, Uppsala University, MoreinX, Dag Hammarskjoldsvag 34 A</s1><s2>751 83 Uppsala</s2><s3>SWE</s3><sZ>9 aut.</sZ></inist:fA14><country>Suède</country><wicri:noRegion>751 83 Uppsala</wicri:noRegion><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Viroscience, Erasmus MC, PO Box 2040</s1><s2>3000 CA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3000 CA Rotterdam</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>ViroClinics Biosciences BV, Marconistraat 16</s1><s2>3029 AK Rotterdam</s2><s3>NLD</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3029 AK Rotterdam</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cellular immunity</term><term>Immunological adjuvant</term><term>Inactivated strain</term><term>Influenza</term><term>T-Lymphocyte</term><term>Vaccination</term><term>Vaccine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Adjuvant immunologique</term><term>Immunité cellulaire</term><term>Vaccination</term><term>Souche inactivée</term><term>Vaccin</term><term>Lymphocyte T</term><term>Grippe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccination</term><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8<sup>+</sup> T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>Suède</li></country><region><li>East Middle Sweden</li><li>Svealand</li></region><settlement><li>Uppsala</li></settlement><orgName><li>Université d'Uppsala</li></orgName></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Van De Sandt, Carolien E" sort="Van De Sandt, Carolien E" uniqKey="Van De Sandt C" first="Carolien E." last="Van De Sandt">Carolien E. Van De Sandt</name></noRegion><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><name sortKey="Geelhoed Mieras, Martina M" sort="Geelhoed Mieras, Martina M" uniqKey="Geelhoed Mieras M" first="Martina M." last="Geelhoed-Mieras">Martina M. Geelhoed-Mieras</name><name sortKey="Kreijtz, Joost H C M" sort="Kreijtz, Joost H C M" uniqKey="Kreijtz J" first="Joost H. C. M." last="Kreijtz">Joost H. C. M. Kreijtz</name><name sortKey="Nieuwkoop, Nella J" sort="Nieuwkoop, Nella J" uniqKey="Nieuwkoop N" first="Nella J." last="Nieuwkoop">Nella J. Nieuwkoop</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><name sortKey="Van De Vijver, David A M C" sort="Van De Vijver, David A M C" uniqKey="Van De Vijver D" first="David A. M. C." last="Van De Vijver">David A. M. C. Van De Vijver</name><name sortKey="Vogelzang Van Trierum, Stella E" sort="Vogelzang Van Trierum, Stella E" uniqKey="Vogelzang Van Trierum S" first="Stella E." last="Vogelzang-Van Trierum">Stella E. Vogelzang-Van Trierum</name></country><country name="Suède"><region name="Svealand"><name sortKey="Morein, Bror" sort="Morein, Bror" uniqKey="Morein B" first="Bror" last="Morein">Bror Morein</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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