SrasV1, Istex, Corpus, bibRecord, 000085

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

Identifieur interne : 000085 ( Istex/Corpus ); précédent : 000084; suivant : 000086

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

Auteurs : Naomi Takasuka ; Hideki Fujii ; Yoshimasa Takahashi ; Masataka Kasai ; Shigeru Morikawa ; Shigeyuki Itamura ; Koji Ishii ; Masahiro Sakaguchi ; Kazuo Ohnishi ; Masamichi Ohshima ; Shu-Ichi Hashimoto ; Takato Odagiri ; Masato Tashiro ; Hiroshi Yoshikura ; Toshitada Takemori ; Yasuko Tsunetsugu-Yokota

Source :

International Immunology [ 0953-8178 ] ; 2004.

RBID : ISTEX:506B90F83AAF56295C5A0D6DAC109CB6DB03EC54

Abstract

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.

Url:

https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/fulltext.pdf

DOI: 10.1093/intimm/dxh143

Links to Exploration step

ISTEX:506B90F83AAF56295C5A0D6DAC109CB6DB03EC54

Le document en format XML

<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
<author><name sortKey="Takasuka, Naomi" sort="Takasuka, Naomi" uniqKey="Takasuka N" first="Naomi" last="Takasuka">Naomi Takasuka</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Fujii, Hideki" sort="Fujii, Hideki" uniqKey="Fujii H" first="Hideki" last="Fujii">Hideki Fujii</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Takahashi, Yoshimasa" sort="Takahashi, Yoshimasa" uniqKey="Takahashi Y" first="Yoshimasa" last="Takahashi">Yoshimasa Takahashi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kasai, Masataka" sort="Kasai, Masataka" uniqKey="Kasai M" first="Masataka" last="Kasai">Masataka Kasai</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Morikawa, Shigeru" sort="Morikawa, Shigeru" uniqKey="Morikawa S" first="Shigeru" last="Morikawa">Shigeru Morikawa</name>
<affiliation><mods:affiliation>First,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Itamura, Shigeyuki" sort="Itamura, Shigeyuki" uniqKey="Itamura S" first="Shigeyuki" last="Itamura">Shigeyuki Itamura</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ishii, Koji" sort="Ishii, Koji" uniqKey="Ishii K" first="Koji" last="Ishii">Koji Ishii</name>
<affiliation><mods:affiliation>Second and</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sakaguchi, Masahiro" sort="Sakaguchi, Masahiro" uniqKey="Sakaguchi M" first="Masahiro" last="Sakaguchi">Masahiro Sakaguchi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ohnishi, Kazuo" sort="Ohnishi, Kazuo" uniqKey="Ohnishi K" first="Kazuo" last="Ohnishi">Kazuo Ohnishi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ohshima, Masamichi" sort="Ohshima, Masamichi" uniqKey="Ohshima M" first="Masamichi" last="Ohshima">Masamichi Ohshima</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hashimoto, Shu Ichi" sort="Hashimoto, Shu Ichi" uniqKey="Hashimoto S" first="Shu-Ichi" last="Hashimoto">Shu-Ichi Hashimoto</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Odagiri, Takato" sort="Odagiri, Takato" uniqKey="Odagiri T" first="Takato" last="Odagiri">Takato Odagiri</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Yoshikura, Hiroshi" sort="Yoshikura, Hiroshi" uniqKey="Yoshikura H" first="Hiroshi" last="Yoshikura">Hiroshi Yoshikura</name>
<affiliation><mods:affiliation>National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Takemori, Toshitada" sort="Takemori, Toshitada" uniqKey="Takemori T" first="Toshitada" last="Takemori">Toshitada Takemori</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tsunetsugu Yokota, Yasuko" sort="Tsunetsugu Yokota, Yasuko" uniqKey="Tsunetsugu Yokota Y" first="Yasuko" last="Tsunetsugu-Yokota">Yasuko Tsunetsugu-Yokota</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:506B90F83AAF56295C5A0D6DAC109CB6DB03EC54</idno>
<date when="2004" year="2004">2004</date>
<idno type="doi">10.1093/intimm/dxh143</idno>
<idno type="url">https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000085</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000085</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main">A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
<author><name sortKey="Takasuka, Naomi" sort="Takasuka, Naomi" uniqKey="Takasuka N" first="Naomi" last="Takasuka">Naomi Takasuka</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Fujii, Hideki" sort="Fujii, Hideki" uniqKey="Fujii H" first="Hideki" last="Fujii">Hideki Fujii</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Takahashi, Yoshimasa" sort="Takahashi, Yoshimasa" uniqKey="Takahashi Y" first="Yoshimasa" last="Takahashi">Yoshimasa Takahashi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kasai, Masataka" sort="Kasai, Masataka" uniqKey="Kasai M" first="Masataka" last="Kasai">Masataka Kasai</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Morikawa, Shigeru" sort="Morikawa, Shigeru" uniqKey="Morikawa S" first="Shigeru" last="Morikawa">Shigeru Morikawa</name>
<affiliation><mods:affiliation>First,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Itamura, Shigeyuki" sort="Itamura, Shigeyuki" uniqKey="Itamura S" first="Shigeyuki" last="Itamura">Shigeyuki Itamura</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ishii, Koji" sort="Ishii, Koji" uniqKey="Ishii K" first="Koji" last="Ishii">Koji Ishii</name>
<affiliation><mods:affiliation>Second and</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sakaguchi, Masahiro" sort="Sakaguchi, Masahiro" uniqKey="Sakaguchi M" first="Masahiro" last="Sakaguchi">Masahiro Sakaguchi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ohnishi, Kazuo" sort="Ohnishi, Kazuo" uniqKey="Ohnishi K" first="Kazuo" last="Ohnishi">Kazuo Ohnishi</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ohshima, Masamichi" sort="Ohshima, Masamichi" uniqKey="Ohshima M" first="Masamichi" last="Ohshima">Masamichi Ohshima</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hashimoto, Shu Ichi" sort="Hashimoto, Shu Ichi" uniqKey="Hashimoto S" first="Shu-Ichi" last="Hashimoto">Shu-Ichi Hashimoto</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Odagiri, Takato" sort="Odagiri, Takato" uniqKey="Odagiri T" first="Takato" last="Odagiri">Takato Odagiri</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name>
<affiliation><mods:affiliation>Third Departments of Virology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Yoshikura, Hiroshi" sort="Yoshikura, Hiroshi" uniqKey="Yoshikura H" first="Hiroshi" last="Yoshikura">Hiroshi Yoshikura</name>
<affiliation><mods:affiliation>National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Takemori, Toshitada" sort="Takemori, Toshitada" uniqKey="Takemori T" first="Toshitada" last="Takemori">Toshitada Takemori</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Tsunetsugu Yokota, Yasuko" sort="Tsunetsugu Yokota, Yasuko" uniqKey="Tsunetsugu Yokota Y" first="Yasuko" last="Tsunetsugu-Yokota">Yasuko Tsunetsugu-Yokota</name>
<affiliation><mods:affiliation>Department of Immunology,</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">International Immunology</title>
<title level="j" type="abbrev">Int. Immunol.</title>
<idno type="ISSN">0953-8178</idno>
<idno type="eISSN">1460-2377</idno>
<imprint><publisher>Oxford University Press</publisher>
<date type="e-published">2004</date>
<date type="published">2004</date>
<biblScope unit="vol">16</biblScope>
<biblScope unit="issue">10</biblScope>
<biblScope unit="page" from="1423">1423</biblScope>
<biblScope unit="page" to="1430">1430</biblScope>
</imprint>
<idno type="ISSN">0953-8178</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0953-8178</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.</div>
</front>
</TEI>
<istex><corpusName>oup</corpusName>
<keywords><teeft><json:string>virion</json:string>
<json:string>coronavirus</json:string>
<json:string>sars</json:string>
<json:string>adjuvant</json:string>
<json:string>immune</json:string>
<json:string>vaccine</json:string>
<json:string>neutralizing</json:string>
<json:string>alum</json:string>
<json:string>igg1</json:string>
<json:string>subcutaneously</json:string>
<json:string>node</json:string>
<json:string>immunogenicity</json:string>
<json:string>coronaviruses</json:string>
<json:string>cytokine</json:string>
<json:string>elisa</json:string>
<json:string>humoral</json:string>
<json:string>vaccinated</json:string>
<json:string>subcutaneous</json:string>
<json:string>virology</json:string>
<json:string>lysates</json:string>
<json:string>high level</json:string>
<json:string>lymph node</json:string>
<json:string>neutralizing activity</json:string>
<json:string>severe acute respiratory syndrome</json:string>
<json:string>bone marrow</json:string>
<json:string>vaccination</json:string>
<json:string>regional lymph node</json:string>
<json:string>novel coronavirus</json:string>
<json:string>alum adjuvant</json:string>
<json:string>neutralizing antibody</json:string>
<json:string>cellular immune response</json:string>
<json:string>immune serum</json:string>
<json:string>subcutaneous injection</json:string>
<json:string>mouse</json:string>
<json:string>mouse inoculated</json:string>
<json:string>animal coronavirus infection</json:string>
<json:string>vaccine candidate</json:string>
<json:string>sars vaccine</json:string>
<json:string>cellular immunity</json:string>
<json:string>igg1 plasma cell</json:string>
<json:string>control mouse</json:string>
<json:string>detection limit</json:string>
<json:string>serum antibody</json:string>
<json:string>nucleocapsid protein</json:string>
<json:string>plasma cell</json:string>
<json:string>immune response</json:string>
<json:string>cytopathic effect</json:string>
<json:string>vaccinia virus</json:string>
<json:string>human coronaviruses</json:string>
<json:string>lymph</json:string>
<json:string>other coronaviruses</json:string>
<json:string>structural protein</json:string>
<json:string>level similar</json:string>
<json:string>antibody production</json:string>
<json:string>culture supernatant</json:string>
<json:string>packard instrument</json:string>
<json:string>memory cell</json:string>
<json:string>parenteral administration</json:string>
<json:string>vaccinated mouse</json:string>
<json:string>monoclonal antibody</json:string>
<json:string>clinical manifestation</json:string>
<json:string>coating antigen</json:string>
<json:string>angiotensinconverting enzyme</json:string>
<json:string>subcutaneously vaccinated mouse</json:string>
<json:string>same dose</json:string>
<json:string>time point</json:string>
<json:string>representative result</json:string>
<json:string>independent experiment</json:string>
<json:string>individual mouse</json:string>
<json:string>aluminum hydroxide</json:string>
<json:string>microtiter plate</json:string>
<json:string>many country</json:string>
<json:string>cell lysates</json:string>
<json:string>cytokine production</json:string>
<json:string>southern biotechnology</json:string>
<json:string>vaccine formula</json:string>
<json:string>subcutaneous vaccination</json:string>
<json:string>separate experiment</json:string>
<json:string>elisa plate</json:string>
<json:string>virus protein</json:string>
<json:string>unit value</json:string>
<json:string>elispot assay</json:string>
<json:string>virionimmunized mouse</json:string>
<json:string>mouse vaccinated</json:string>
<json:string>single cell suspension</json:string>
<json:string>susceptible mouse</json:string>
<json:string>vaccination protocol</json:string>
<json:string>sars coronavirus</json:string>
<json:string>chick embryo</json:string>
</teeft>
</keywords>
<author><json:item><name>Naomi Takasuka</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Hideki Fujii</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Yoshimasa Takahashi</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Masataka Kasai</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Shigeru Morikawa</name>
<affiliations><json:string>First,</json:string>
</affiliations>
</json:item>
<json:item><name>Shigeyuki Itamura</name>
<affiliations><json:string>Third Departments of Virology,</json:string>
</affiliations>
</json:item>
<json:item><name>Koji Ishii</name>
<affiliations><json:string>Second and</json:string>
</affiliations>
</json:item>
<json:item><name>Masahiro Sakaguchi</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Kazuo Ohnishi</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Masamichi Ohshima</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Shu-ichi Hashimoto</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Takato Odagiri</name>
<affiliations><json:string>Third Departments of Virology,</json:string>
</affiliations>
</json:item>
<json:item><name>Masato Tashiro</name>
<affiliations><json:string>Third Departments of Virology,</json:string>
</affiliations>
</json:item>
<json:item><name>Hiroshi Yoshikura</name>
<affiliations><json:string>National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</json:string>
</affiliations>
</json:item>
<json:item><name>Toshitada Takemori</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
<json:item><name>Yasuko Tsunetsugu-Yokota</name>
<affiliations><json:string>Department of Immunology,</json:string>
</affiliations>
</json:item>
</author>
<subject><json:item><lang><json:string>eng</json:string>
</lang>
<value>alum</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>cellular immunity</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>neutralizing antibody</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>parenteral administration</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>vaccination</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>ACE2    angiotensin-converting enzyme 2</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>ASC    antibody-secreting cell</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>E    envelope</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>M    membrane</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>N    nucleocapsid protein</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>SARS    severe acute respiratory syndrome</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>SARS-CoV    SARS-associated coronavirus</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>S    spike protein</value>
</json:item>
</subject>
<arkIstex>ark:/67375/HXZ-PDNM495K-Q</arkIstex>
<language><json:string>eng</json:string>
</language>
<originalGenre><json:string>other</json:string>
</originalGenre>
<abstract>The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.</abstract>
<qualityIndicators><score>7.724</score>
<pdfWordCount>5161</pdfWordCount>
<pdfCharCount>32185</pdfCharCount>
<pdfVersion>1.3</pdfVersion>
<pdfPageCount>8</pdfPageCount>
<pdfPageSize>612 x 794 pts</pdfPageSize>
<pdfWordsPerPage>645</pdfWordsPerPage>
<pdfText>true</pdfText>
<refBibsNative>true</refBibsNative>
<abstractWordCount>227</abstractWordCount>
<abstractCharCount>1510</abstractCharCount>
<keywordCount>13</keywordCount>
</qualityIndicators>
<title>A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
<pmid><json:string>15314040</json:string>
</pmid>
<genre><json:string>other</json:string>
</genre>
<host><title>International Immunology</title>
<language><json:string>unknown</json:string>
</language>
<issn><json:string>0953-8178</json:string>
</issn>
<eissn><json:string>1460-2377</json:string>
</eissn>
<publisherId><json:string>intimm</json:string>
</publisherId>
<volume>16</volume>
<issue>10</issue>
<pages><first>1423</first>
<last>1430</last>
</pages>
<genre><json:string>journal</json:string>
</genre>
</host>
<namedEntities><unitex><date><json:string>1-23-1</json:string>
<json:string>2004-08-16</json:string>
<json:string>2002</json:string>
</date>
<geogName></geogName>
<orgName><json:string>Packard Instruments</json:string>
<json:string>Department of Immunology</json:string>
<json:string>National Institute of Infectious Diseases, Toyama</json:string>
<json:string>Southern Biotechnology</json:string>
<json:string>Southern Biotechnology, Birmingham</json:string>
<json:string>Jackson Immuno Research, West Grove, PA</json:string>
<json:string>Nippon SLC Inc.</json:string>
<json:string>Department of Microbiology, The University of Hong Kong</json:string>
<json:string>Japan Keywords</json:string>
<json:string>Dynatech</json:string>
<json:string>Ministry of Public Health</json:string>
<json:string>Labor of Japan</json:string>
</orgName>
<orgName_funder><json:string>Ministry of Public Health</json:string>
<json:string>Labor of Japan</json:string>
</orgName_funder>
<orgName_provider></orgName_provider>
<persName><json:string>Ms R. Ishida</json:string>
<json:string>Y. Kaburagi</json:string>
<json:string>J.S.M. Peiris</json:string>
<json:string>Costa Mesa</json:string>
<json:string>Y. Tsunetsugu-Yokota</json:string>
<json:string>Kazuo Ohnishi</json:string>
<json:string>K. Sugamura</json:string>
<json:string>Y. Kimishima</json:string>
</persName>
<placeName><json:string>Bedford</json:string>
<json:string>Meriden</json:string>
<json:string>Rochester</json:string>
<json:string>Germany</json:string>
<json:string>Chantily</json:string>
<json:string>NY</json:string>
<json:string>Shizuoka</json:string>
<json:string>VA</json:string>
<json:string>Immunogenicity</json:string>
<json:string>San Jose</json:string>
<json:string>China</json:string>
<json:string>Japan</json:string>
<json:string>CT</json:string>
<json:string>San Francisco</json:string>
<json:string>Puri</json:string>
<json:string>Tokyo</json:string>
<json:string>CA</json:string>
<json:string>MA</json:string>
<json:string>Bergisch Gladbach</json:string>
</placeName>
<ref_url></ref_url>
<ref_bibl><json:string>Xiao et al.</json:string>
<json:string>March 2003</json:string>
</ref_bibl>
<bibl></bibl>
</unitex>
</namedEntities>
<ark><json:string>ark:/67375/HXZ-PDNM495K-Q</json:string>
</ark>
<categories><wos><json:string>1 - science</json:string>
<json:string>2 - immunology</json:string>
</wos>
<scienceMetrix><json:string>1 - health sciences</json:string>
<json:string>2 - clinical medicine</json:string>
<json:string>3 - immunology</json:string>
</scienceMetrix>
<scopus><json:string>1 - Life Sciences</json:string>
<json:string>2 - Immunology and Microbiology</json:string>
<json:string>3 - Immunology</json:string>
<json:string>1 - Health Sciences</json:string>
<json:string>2 - Medicine</json:string>
<json:string>3 - General Medicine</json:string>
</scopus>
<inist><json:string>1 - sciences appliquees, technologies et medecines</json:string>
<json:string>2 - sciences biologiques et medicales</json:string>
<json:string>3 - sciences biologiques fondamentales et appliquees. psychologie</json:string>
<json:string>4 - invertebres</json:string>
</inist>
</categories>
<publicationDate>2004</publicationDate>
<copyrightDate>2004</copyrightDate>
<doi><json:string>10.1093/intimm/dxh143</json:string>
</doi>
<id>506B90F83AAF56295C5A0D6DAC109CB6DB03EC54</id>
<score>1</score>
<fulltext><json:item><extension>pdf</extension>
<original>true</original>
<mimetype>application/pdf</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/fulltext.pdf</uri>
</json:item>
<json:item><extension>zip</extension>
<original>false</original>
<mimetype>application/zip</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/bundle.zip</uri>
</json:item>
<istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
</titleStmt>
<publicationStmt><authority>ISTEX</authority>
<publisher>Oxford University Press</publisher>
<availability><licence>© 2004 The Japanese Society for Immunology</licence>
</availability>
<date type="published">2004</date>
<date type="Copyright" when="2004">2004</date>
</publicationStmt>
<notesStmt><note type="content-type" source="other" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note>
<note type="publication-type" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note>
</notesStmt>
<sourceDesc><biblStruct type="other"><analytic><title level="a" type="main">A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
<author xml:id="author-0000"><persName><surname>Takasuka</surname>
<forename type="first">Naomi</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0001"><persName><surname>Fujii</surname>
<forename type="first">Hideki</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0002"><persName><surname>Takahashi</surname>
<forename type="first">Yoshimasa</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0003"><persName><surname>Kasai</surname>
<forename type="first">Masataka</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0004"><persName><surname>Morikawa</surname>
<forename type="first">Shigeru</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0005"><persName><surname>Itamura</surname>
<forename type="first">Shigeyuki</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0006"><persName><surname>Ishii</surname>
<forename type="first">Koji</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0007"><persName><surname>Sakaguchi</surname>
<forename type="first">Masahiro</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0008"><persName><surname>Ohnishi</surname>
<forename type="first">Kazuo</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0009"><persName><surname>Ohshima</surname>
<forename type="first">Masamichi</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0010"><persName><surname>Hashimoto</surname>
<forename type="first">Shu-ichi</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0011"><persName><surname>Odagiri</surname>
<forename type="first">Takato</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0012"><persName><surname>Tashiro</surname>
<forename type="first">Masato</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0013"><persName><surname>Yoshikura</surname>
<forename type="first">Hiroshi</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0014"><persName><surname>Takemori</surname>
<forename type="first">Toshitada</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<author xml:id="author-0015"><persName><surname>Tsunetsugu-Yokota</surname>
<forename type="first">Yasuko</forename>
</persName>
<affiliation role="corresp">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</affiliation>
</author>
<idno type="istex">506B90F83AAF56295C5A0D6DAC109CB6DB03EC54</idno>
<idno type="ark">ark:/67375/HXZ-PDNM495K-Q</idno>
<idno type="other">dxh143</idno>
<idno type="DOI">10.1093/intimm/dxh143</idno>
</analytic>
<monogr><title level="j" type="main">International Immunology</title>
<title level="j" type="abbrev">Int. Immunol.</title>
<idno type="hwp">intimm</idno>
<idno type="nlm-ta">Int Immunol</idno>
<idno type="publisher-id">intimm</idno>
<idno type="pISSN">0953-8178</idno>
<idno type="eISSN">1460-2377</idno>
<imprint><publisher>Oxford University Press</publisher>
<date type="e-published">2004</date>
<date type="published">2004</date>
<biblScope unit="vol">16</biblScope>
<biblScope unit="issue">10</biblScope>
<biblScope unit="page" from="1423">1423</biblScope>
<biblScope unit="page" to="1430">1430</biblScope>
</imprint>
</monogr>
</biblStruct>
</sourceDesc>
</fileDesc>
<encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef>
<appInfo><application ident="pub2tei" version="1.0.41" when="2020-04-06"><label>pub2TEI-ISTEX</label>
<desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
                        <ref target="http://www.tei-c.org/">We use TEI</ref>
</desc>
</application>
</appInfo>
</encodingDesc>
<profileDesc><abstract xml:lang="en"><p>The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion <hi rend="italic">in vitro</hi>
. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.</p>
</abstract>
<textClass ana="subject"><keywords scheme="heading"><term>ORIGINAL RESEARCH PAPERS</term>
</keywords>
</textClass>
<textClass ana="keyword"><keywords scheme="KWD" xml:lang="en"><term>alum</term>
<term>cellular immunity</term>
<term>neutralizing antibody</term>
<term>parenteral administration</term>
<term>vaccination</term>
</keywords>
</textClass>
<textClass ana="keyword"><keywords scheme="ABR" xml:lang="en"><term>ACE2    angiotensin-converting enzyme 2</term>
<term>ASC    antibody-secreting cell</term>
<term>E    envelope</term>
<term>M    membrane</term>
<term>N    nucleocapsid protein</term>
<term>SARS    severe acute respiratory syndrome</term>
<term>SARS-CoV    SARS-associated coronavirus</term>
<term>S    spike protein</term>
</keywords>
</textClass>
<langUsage><language ident="en"></language>
</langUsage>
</profileDesc>
<revisionDesc><change when="2020-04-06" who="#istex" xml:id="pub2tei">formatting</change>
</revisionDesc>
</teiHeader>
</istex:fulltextTEI>
<json:item><extension>txt</extension>
<original>false</original>
<mimetype>text/plain</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/fulltext.txt</uri>
</json:item>
</fulltext>
<metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration>
<istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType>
<istex:document><article xml:lang="en" article-type="other"><front><journal-meta><journal-id journal-id-type="hwp">intimm</journal-id>
<journal-id journal-id-type="nlm-ta">Int Immunol</journal-id>

<journal-id journal-id-type="publisher-id">intimm</journal-id>
<journal-title>International Immunology</journal-title>
<abbrev-journal-title abbrev-type="publisher">Int. Immunol.</abbrev-journal-title>
<issn pub-type="ppub">0953-8178</issn>
<issn pub-type="epub">1460-2377</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="other">dxh143</article-id>
<article-id pub-id-type="doi">10.1093/intimm/dxh143</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>ORIGINAL RESEARCH PAPERS</subject>
</subj-group>
</article-categories>
<title-group><article-title>A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</article-title>
</title-group>
<contrib-group>

      <contrib contrib-type="author"><name><surname>Takasuka</surname>
<given-names>Naomi</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Fujii</surname>
<given-names>Hideki</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Takahashi</surname>
<given-names>Yoshimasa</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Kasai</surname>
<given-names>Masataka</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Morikawa</surname>
<given-names>Shigeru</given-names>
</name>

        

        

      

      <xref rid="AFF2">

        <sup>2</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Itamura</surname>
<given-names>Shigeyuki</given-names>
</name>

        

        

      

      <xref rid="AFF4">

        <sup>4</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Ishii</surname>
<given-names>Koji</given-names>
</name>

        

        

      

      <xref rid="AFF3">

        <sup>3</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Sakaguchi</surname>
<given-names>Masahiro</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Ohnishi</surname>
<given-names>Kazuo</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Ohshima</surname>
<given-names>Masamichi</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Hashimoto</surname>
<given-names>Shu-ichi</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Odagiri</surname>
<given-names>Takato</given-names>
</name>

        

        

      

      <xref rid="AFF4">

        <sup>4</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Tashiro</surname>
<given-names>Masato</given-names>
</name>

        

        

      

      <xref rid="AFF4">

        <sup>4</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Yoshikura</surname>
<given-names>Hiroshi</given-names>
</name>

        

        

      

      <xref rid="AFF5">

        <sup>5</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Takemori</surname>
<given-names>Toshitada</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      </contrib>
<contrib contrib-type="author"><name><surname>Tsunetsugu-Yokota</surname>
<given-names>Yasuko</given-names>
</name>

        

        

      

      <xref rid="AFF1">

        <sup>1</sup>

      </xref>

      

      

    </contrib>
<aff><target target-type="aff" id="AFF1"></target>
<label>1</label>
Department of Immunology, <target target-type="aff" id="AFF2"></target>
<label>2</label>
First, <target target-type="aff" id="AFF3"></target>
<label>3</label>
Second and <target target-type="aff" id="AFF4"></target>
<label>4</label>
Third Departments of Virology, <target target-type="aff" id="AFF5"></target>
<label>5</label>
National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</aff>
</contrib-group>
<author-notes><corresp><italic>Correspondence to</italic>
: Y. Tsunetsugu-Yokota; E-mail: <ext-link xlink:href="yyokota@nih.go.jp" ext-link-type="email">yyokota@nih.go.jp</ext-link>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>16</day>
<month>8</month>
<year>2004</year>
</pub-date>
<pub-date pub-type="ppub"><month>10</month>
<year>2004</year>
</pub-date>
<volume>16</volume>
<issue>10</issue>
<fpage>1423</fpage>
<lpage>1430</lpage>
<history><date date-type="accepted"><day>15</day>
<month>7</month>
<year>2004</year>
</date>
<date date-type="received"><day>6</day>
<month>5</month>
<year>2004</year>
</date>
</history>
<permissions><copyright-statement>© 2004 The Japanese Society for Immunology</copyright-statement>
<copyright-year>2004</copyright-year>
</permissions>
<abstract xml:lang="en">

      <p>The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion <italic>in vitro</italic>
. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.</p>

    </abstract>
<kwd-group kwd-group-type="KWD" xml:lang="en">

      <kwd>alum</kwd>

      <kwd>cellular immunity</kwd>

      <kwd>neutralizing antibody</kwd>

      <kwd>parenteral administration</kwd>

      <kwd>vaccination</kwd>

    </kwd-group>
<kwd-group kwd-group-type="ABR" xml:lang="en">

      <kwd>ACE2    angiotensin-converting enzyme 2</kwd>

      <kwd>ASC    antibody-secreting cell</kwd>

      <kwd>E    envelope</kwd>

      <kwd>M    membrane</kwd>

      <kwd>N    nucleocapsid protein</kwd>

      <kwd>SARS    severe acute respiratory syndrome</kwd>

      <kwd>SARS-CoV    SARS-associated coronavirus</kwd>

      <kwd>S    spike protein</kwd>

    </kwd-group>
<custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name>
<meta-value>1423</meta-value>
</custom-meta>
<custom-meta><meta-name>hwp-legacy-dochead</meta-name>
<meta-value>Original Research Paper</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>

  

  

  

  

    

    

    

    

    

    

    

    

    

  

  

  

    

    

  

</article>
</istex:document>
</istex:metadataXml>
<mods version="3.6"><titleInfo lang="en"><title>A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
</titleInfo>
<titleInfo type="alternative" lang="en" contentType="CDATA"><title>A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice</title>
</titleInfo>
<name type="personal"><namePart type="given">Naomi</namePart>
<namePart type="family">Takasuka</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Hideki</namePart>
<namePart type="family">Fujii</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yoshimasa</namePart>
<namePart type="family">Takahashi</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Masataka</namePart>
<namePart type="family">Kasai</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Shigeru</namePart>
<namePart type="family">Morikawa</namePart>
<affiliation>First,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Shigeyuki</namePart>
<namePart type="family">Itamura</namePart>
<affiliation>Third Departments of Virology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Koji</namePart>
<namePart type="family">Ishii</namePart>
<affiliation>Second and</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Masahiro</namePart>
<namePart type="family">Sakaguchi</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Kazuo</namePart>
<namePart type="family">Ohnishi</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Masamichi</namePart>
<namePart type="family">Ohshima</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Shu-ichi</namePart>
<namePart type="family">Hashimoto</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Takato</namePart>
<namePart type="family">Odagiri</namePart>
<affiliation>Third Departments of Virology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Masato</namePart>
<namePart type="family">Tashiro</namePart>
<affiliation>Third Departments of Virology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Hiroshi</namePart>
<namePart type="family">Yoshikura</namePart>
<affiliation>National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Toshitada</namePart>
<namePart type="family">Takemori</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yasuko</namePart>
<namePart type="family">Tsunetsugu-Yokota</namePart>
<affiliation>Department of Immunology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<typeOfResource>text</typeOfResource>
<genre type="other" displayLabel="other" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-7474895G-0">other</genre>
<originInfo><publisher>Oxford University Press</publisher>
<dateIssued encoding="w3cdtf">2004-10</dateIssued>
<dateCreated encoding="w3cdtf">2004-07-15</dateCreated>
<copyrightDate encoding="w3cdtf">2004</copyrightDate>
</originInfo>
<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
</language>
<abstract lang="en">The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-γ and TNF-α) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.</abstract>
<note type="author-notes">Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota@nih.go.jp</note>
<subject lang="en"><genre>KWD</genre>
<topic>alum</topic>
<topic>cellular immunity</topic>
<topic>neutralizing antibody</topic>
<topic>parenteral administration</topic>
<topic>vaccination</topic>
</subject>
<subject lang="en"><genre>ABR</genre>
<topic>ACE2    angiotensin-converting enzyme 2</topic>
<topic>ASC    antibody-secreting cell</topic>
<topic>E    envelope</topic>
<topic>M    membrane</topic>
<topic>N    nucleocapsid protein</topic>
<topic>SARS    severe acute respiratory syndrome</topic>
<topic>SARS-CoV    SARS-associated coronavirus</topic>
<topic>S    spike protein</topic>
</subject>
<relatedItem type="host"><titleInfo><title>International Immunology</title>
</titleInfo>
<titleInfo type="abbreviated"><title>Int. Immunol.</title>
</titleInfo>
<genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre>
<identifier type="ISSN">0953-8178</identifier>
<identifier type="eISSN">1460-2377</identifier>
<identifier type="PublisherID">intimm</identifier>
<identifier type="PublisherID-hwp">intimm</identifier>
<identifier type="PublisherID-nlm-ta">Int Immunol</identifier>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>16</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>10</number>
</detail>
<extent unit="pages"><start>1423</start>
<end>1430</end>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB1"><titleInfo><title>N. Engl. J. Med.</title>
</titleInfo>
<note>Drosten, C., Gunther, S., Preiser, W. et al. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348:1967.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>348</number>
</detail>
<extent unit="pages"><start>1967</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB2"><titleInfo><title>N. Engl. J. Med.</title>
</titleInfo>
<note>Ksiazek, T. G., Erdman, D., Goldsmith, C. S. et al. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348:1953.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>348</number>
</detail>
<extent unit="pages"><start>1953</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB3"><titleInfo><title>Science</title>
</titleInfo>
<note>Marra, M. A., Jones, S. J., Astell, C. R. et al. 2003. The genome sequence of the SARS-associated coronavirus. Science 300:1399.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>300</number>
</detail>
<extent unit="pages"><start>1399</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB4"><titleInfo><title>Science</title>
</titleInfo>
<note>Rota, P. A., Oberste, M. S., Monroe, S. S. et al. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>300</number>
</detail>
<extent unit="pages"><start>1394</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB5"><titleInfo><title>Science</title>
</titleInfo>
<note>Holmes, K. V. and Enjuanes, L. 2003. Virology. The SARS coronavirus: a postgenomic era. Science 300:1377.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>300</number>
</detail>
<extent unit="pages"><start>1377</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB6"><titleInfo><title>Clin. Diagn. Lab. Immunol.</title>
</titleInfo>
<note>Liu, X., Shi, Y., Li, P., Li, L., Yi, Y., Ma, Q. and Cao, C. 2004. Profile of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)-associated coronavirus in probable SARS patients. Clin. Diagn. Lab. Immunol. 11:227.</note>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>11</number>
</detail>
<extent unit="pages"><start>227</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB7"><titleInfo><title>Vaccine</title>
</titleInfo>
<note>De Groot, A. S. 2003. How the SARS vaccine effort can learn from HIV—speeding towards the future, learning from the past. Vaccine 21:4095.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>21</number>
</detail>
<extent unit="pages"><start>4095</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB8"><titleInfo><title>Nature</title>
</titleInfo>
<note>Li, W., Moore, M. J., Vasilieva, N. et al. 2003. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>426</number>
</detail>
<extent unit="pages"><start>450</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB9"><titleInfo><title>Virology</title>
</titleInfo>
<note>Collins, R. A., Knobler, R. L., Powell, H. and Buchmeier, M. J. 1982. Monoclonal antibodies to murine hepatitis virus-4 (strain JHM) define the viral glycoprotein responsible for attachment and cell–cell fusion. Virology 119:358.</note>
<part><date>1982</date>
<detail type="volume"><caption>vol.</caption>
<number>119</number>
</detail>
<extent unit="pages"><start>358</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB10"><titleInfo><title>Virology</title>
</titleInfo>
<note>Fleming, J. O., Stohlman, S. A., Harmon, R. C., Lai, M. M., Frelinger, J. A. and Weiner, L. P. 1983. Antigenic relationship of murine coronaviruses: analysis using monoclonal antibodies to JHM (MHV-4) virus. Virology 131:296.</note>
<part><date>1983</date>
<detail type="volume"><caption>vol.</caption>
<number>131</number>
</detail>
<extent unit="pages"><start>296</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB11"><titleInfo><title>Adv. Exp. Med. Biol.</title>
</titleInfo>
<note>Jackwood, M. W. and Hilt, D. A. 1995. Production and immunogenicity of multiple antigenic peptide (MAP) constructs derived from the S1 glycoprotein of infectious bronchitis virus (IBV). Adv. Exp. Med. Biol. 380:213.</note>
<part><date>1995</date>
<detail type="volume"><caption>vol.</caption>
<number>380</number>
</detail>
<extent unit="pages"><start>213</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB12"><titleInfo><title>Virus Res.</title>
</titleInfo>
<note>Anton, I. M., Gonzalez, S., Bullido, M. J., Corsin, M., Risco, C., Langeveld, J. P. and Enjuanes, L. 1996. Cooperation between transmissible gastroenteritis coronavirus (TGEV) structural proteins in the in vitro induction of virus-specific antibodies. Virus Res. 46:111.</note>
<part><date>1996</date>
<detail type="volume"><caption>vol.</caption>
<number>46</number>
</detail>
<extent unit="pages"><start>111</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB13"><titleInfo><title>Virology</title>
</titleInfo>
<note>Ishii, K., Ueda, Y., Matsuo, K. et al. 2002. Structural analysis of vaccinia virus DIs strain: application as a new replication-deficient viral vector. Virology 302:433.</note>
<part><date>2002</date>
<detail type="volume"><caption>vol.</caption>
<number>302</number>
</detail>
<extent unit="pages"><start>433</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB14"><titleInfo><title>Fields Virology</title>
</titleInfo>
<note>Storch, G. A. 2001. Diagnostic virology. In Knipe, D. M., Howley, P. M., ed., Fields Virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, PA. pp. 493–531.</note>
<part><date>2001</date>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB15"><titleInfo><title>Clin. Exp. Immunol.</title>
</titleInfo>
<note>Benner, R., Hijmans, W. and Haaijman, J. J. 1981. The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. Clin. Exp. Immunol. 46:1.</note>
<part><date>1981</date>
<detail type="volume"><caption>vol.</caption>
<number>46</number>
</detail>
<extent unit="pages"><start>1</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB16"><titleInfo><title>J. Virol.</title>
</titleInfo>
<note>Slifka, M. K., Matloubian, M. and Ahmed, R. 1995. Bone marrow is a major site of long-term antibody production after acute viral infection. J. Virol. 69:1895.</note>
<part><date>1995</date>
<detail type="volume"><caption>vol.</caption>
<number>69</number>
</detail>
<extent unit="pages"><start>1895</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB17"><titleInfo><title>Infect. Immun.</title>
</titleInfo>
<note>Schmidt, O. W. and Kenny, G. E. 1982. Polypeptides and functions of antigens from human coronaviruses 229E and OC43. Infect. Immun. 35:515.</note>
<part><date>1982</date>
<detail type="volume"><caption>vol.</caption>
<number>35</number>
</detail>
<extent unit="pages"><start>515</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB18"><titleInfo><title>Biochem. Biophys. Res. Commun.</title>
</titleInfo>
<note>Xiao, X., Chakraborti, S., Dimitrov, A. S., Gramatikoff, K. and Dimitrov, D. S. 2003. The SARS-CoV S glycoprotein: expression and functional characterization. Biochem. Biophys. Res. Commun. 312:1159.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>312</number>
</detail>
<extent unit="pages"><start>1159</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB19"><titleInfo><title>Nat. Biotechnol.</title>
</titleInfo>
<note>Singh, M. and O'Hagan, D. 1999. Advances in vaccine adjuvants. Nat. Biotechnol. 17:1075.</note>
<part><date>1999</date>
<detail type="volume"><caption>vol.</caption>
<number>17</number>
</detail>
<extent unit="pages"><start>1075</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB20"><titleInfo><title>Vaccine</title>
</titleInfo>
<note>Clements, C. J. and Griffiths, E. 2002. The global impact of vaccines containing aluminium adjuvants. Vaccine 20 (Suppl. 3): S24.</note>
<part><date>2002</date>
<detail type="volume"><caption>vol.</caption>
<number>20</number>
</detail>
<extent unit="pages"><start>S24</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB21"><titleInfo><title>Vaccine</title>
</titleInfo>
<note>HogenEsch, H. 2002. Mechanisms of stimulation of the immune response by aluminum adjuvants. Vaccine 20 (Suppl. 3): S34.</note>
<part><date>2002</date>
<detail type="volume"><caption>vol.</caption>
<number>20</number>
</detail>
<extent unit="pages"><start>S34</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB22"><titleInfo><title>Science</title>
</titleInfo>
<note>Jordan, M. B., Mills, D. M., Kappler, J., Marrack, P. and Cambier, J. C. 2004. Promotion of B cell immune responses via an alum-induced myeloid cell population. Science 304:1808.</note>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>304</number>
</detail>
<extent unit="pages"><start>1808</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB23"><titleInfo><title>Comp. Immunol. Microbiol. Infect. Dis.</title>
</titleInfo>
<note>Weiss, R. C. and Scott, F. W. 1981. Antibody-mediated enhancement of disease in feline infectious peritonitis: comparisons with dengue hemorrhagic fever. Comp. Immunol. Microbiol. Infect. Dis. 4:175.</note>
<part><date>1981</date>
<detail type="volume"><caption>vol.</caption>
<number>4</number>
</detail>
<extent unit="pages"><start>175</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB24"><titleInfo><title>Adv. Exp. Med. Biol.</title>
</titleInfo>
<note>Wu, G. F., Dandekar, A. A., Pewe, L. and Perlman, S. 2001. The role of CD4 and CD8 T cells in MHV-JHM-induced demyelination. Adv. Exp. Med. Biol. 494:341.</note>
<part><date>2001</date>
<detail type="volume"><caption>vol.</caption>
<number>494</number>
</detail>
<extent unit="pages"><start>341</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB25"><titleInfo><title>J. Immunol.</title>
</titleInfo>
<note>Pope, M., Chung, S. W., Mosmann, T., Leibowitz, J. L., Gorczynski, R. M. and Levy, G. A. 1996. Resistance of naive mice to murine hepatitis virus strain 3 requires development of a Th1, but not a Th2, response, whereas pre-existing antibody partially protects against primary infection. J. Immunol. 156:3342.</note>
<part><date>1996</date>
<detail type="volume"><caption>vol.</caption>
<number>156</number>
</detail>
<extent unit="pages"><start>3342</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB26"><titleInfo><title>Nature</title>
</titleInfo>
<note>Yang, Z. Y., Kong, W. P., Huang, Y., Roberts, A., Murphy, B. R., Subbarao, K. and Nabel, G. J. 2004. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428:561.</note>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>428</number>
</detail>
<extent unit="pages"><start>561</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB27"><titleInfo><title>Vaccine</title>
</titleInfo>
<note>Mazumdar, T., Anam, K. and Ali N. 2004. A mixed Th1/Th2 response elicited by a liposomal formation of Leishmania vaccine instructs Th1 responses and resistance to Leishmania donovani in susceptible BALB/c mice. Vaccine 22:1162.</note>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>22</number>
</detail>
<extent unit="pages"><start>1162</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB28"><titleInfo><title>Vaccine</title>
</titleInfo>
<note>Nicollier-Jamot, B., Ogier, A., Piroth, L., Pothier, P. and Kohli, E. 2004. Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in BALB/c mice induce specific humoral and cellular Th1/Th2-like immune responses. Vaccine 22:1079.</note>
<part><date>2004</date>
<detail type="volume"><caption>vol.</caption>
<number>22</number>
</detail>
<extent unit="pages"><start>1079</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB29"><titleInfo><title>Lancet</title>
</titleInfo>
<note>Gao, W., Tamin, A., Soloff, A., D'Aiuto, L., Nwanegbo, E., Robbins, P. D., Bellini, W. J., Barratt-Boyes, S. and Gambotto, A. 2003. Effects of a SARS-associated coronavirus vaccine in monkeys. Lancet 362:1895.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>362</number>
</detail>
<extent unit="pages"><start>1895</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB30"><titleInfo><title>Can. J. Vet. Res.</title>
</titleInfo>
<note>Takamura, K., Matsumoto, Y. and Shimizu, Y. 2002. Field study of bovine coronavirus vaccine enriched with hemagglutinating antigen for winter dysentery in dairy cows. Can. J. Vet. Res. 66:278.</note>
<part><date>2002</date>
<detail type="volume"><caption>vol.</caption>
<number>66</number>
</detail>
<extent unit="pages"><start>278</start>
</extent>
</part>
</relatedItem>
<relatedItem type="references" displayLabel="BIB31"><titleInfo><title>New Microbiol.</title>
</titleInfo>
<note>Pratelli, A., Tinelli, A., Decaro, N., Cirone, F., Elia, G., Roperto, S., Tempesta, M. and Buonavoglia, C. 2003. Efficacy of an inactivated canine coronavirus vaccine in pups. New Microbiol. 26:151.</note>
<part><date>2003</date>
<detail type="volume"><caption>vol.</caption>
<number>26</number>
</detail>
<extent unit="pages"><start>151</start>
</extent>
</part>
</relatedItem>
<identifier type="istex">506B90F83AAF56295C5A0D6DAC109CB6DB03EC54</identifier>
<identifier type="ark">ark:/67375/HXZ-PDNM495K-Q</identifier>
<identifier type="DOI">10.1093/intimm/dxh143</identifier>
<identifier type="local">dxh143</identifier>
<accessCondition type="use and reproduction" contentType="copyright">© 2004 The Japanese Society for Immunology</accessCondition>
<recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource>
<recordOrigin>Converted from  (version 1.2.10) to MODS version 3.6.</recordOrigin>
<recordCreationDate encoding="w3cdtf">2020-04-17</recordCreationDate>
</recordInfo>
</mods>
<json:item><extension>json</extension>
<original>false</original>
<mimetype>application/json</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/record.json</uri>
</json:item>
</metadata>
<annexes><json:item><extension>gif</extension>
<original>true</original>
<mimetype>image/gif</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/annexes.gif</uri>
</json:item>
<json:item><extension>jpeg</extension>
<original>true</original>
<mimetype>image/jpeg</mimetype>
<uri>https://api.istex.fr/ark:/67375/HXZ-PDNM495K-Q/annexes.jpeg</uri>
</json:item>
</annexes>
<serie></serie>
</istex>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Istex/Corpus

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000085 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000085 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Istex
   |étape=   Corpus
   |type=    RBID
   |clé=     ISTEX:506B90F83AAF56295C5A0D6DAC109CB6DB03EC54
   |texte=   A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice
}}

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

	Serveur d'exploration SRAS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration SRAS

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

Source :

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri