A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice
Identifieur interne : 000085 ( Istex/Corpus ); précédent : 000084; suivant : 000086A 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-YokotaSource :
- International Immunology [ 0953-8178 ] ; 2004.
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:
DOI: 10.1093/intimm/dxh143
Links to Exploration step
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<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>
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<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>
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<author xml:id="author-0003"><persName><surname>Kasai</surname>
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<author xml:id="author-0004"><persName><surname>Morikawa</surname>
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<given-names>Naomi</given-names>
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<xref rid="AFF1">
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<given-names>Shigeru</given-names>
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<given-names>Shigeyuki</given-names>
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<xref rid="AFF4">
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<xref rid="AFF1">
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<xref rid="AFF4">
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<xref rid="AFF4">
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<name type="personal"><namePart type="given">Shigeyuki</namePart>
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<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>
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<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
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<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>
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<identifier type="ISSN">0953-8178</identifier>
<identifier type="eISSN">1460-2377</identifier>
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<identifier type="PublisherID-hwp">intimm</identifier>
<identifier type="PublisherID-nlm-ta">Int Immunol</identifier>
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