SrasV1, Main, Exploration, bibRecord, 001528

Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

Identifieur interne : 001528 ( Main/Exploration ); précédent : 001527; suivant : 001529

Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

Auteurs : Wen-Hsiang Chen [États-Unis] ; Lanying Du [États-Unis] ; Shivali M. Chag [États-Unis] ; Cuiqing Ma [États-Unis] ; Nancy Tricoche [États-Unis] ; Xinrong Tao [États-Unis] ; Christopher A. Seid [États-Unis] ; Elissa M. Hudspeth [États-Unis] ; Sara Lustigman [États-Unis] ; Chien-Te K. Tseng [États-Unis] ; Maria Elena Bottazzi [États-Unis] ; Peter J. Hotez [États-Unis] ; Bin Zhan [États-Unis] ; Shibo Jiang [République populaire de Chine]

Source :

Human vaccines & immunotherapeutics [ 2164-554X ] ; 2014.

RBID : pubmed:24355931

Descripteurs français

English descriptors

KwdEn :
- Adjuvants, Immunologic (administration & dosage), Alum Compounds (administration & dosage), Animals, Female, Gene Expression, Glycosylation, Mice, Inbred BALB C, Pichia (genetics), Recombinant Proteins (genetics), Recombinant Proteins (immunology), SARS Virus (immunology), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (genetics), Viral Vaccines (immunology).
MESH :
- chemical , administration & dosage : Adjuvants, Immunologic, Alum Compounds, Vaccines, Synthetic, Viral Vaccines.
- genetics : Pichia, Recombinant Proteins, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- chemical , immunology : Recombinant Proteins, SARS Virus, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, Viral Vaccines.
- Animals, Female, Gene Expression, Glycosylation, Mice, Inbred BALB C.

Abstract

Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.

DOI: 10.4161/hv.27464
PubMed: 24355931

Affiliations:

Le document en format XML

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<author><name sortKey="Lustigman, Sara" sort="Lustigman, Sara" uniqKey="Lustigman S" first="Sara" last="Lustigman">Sara Lustigman</name>
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<author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
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<author><name sortKey="Bottazzi, Maria Elena" sort="Bottazzi, Maria Elena" uniqKey="Bottazzi M" first="Maria Elena" last="Bottazzi">Maria Elena Bottazzi</name>
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</placeName>
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</affiliation>
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<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.</title>
<author><name sortKey="Chen, Wen Hsiang" sort="Chen, Wen Hsiang" uniqKey="Chen W" first="Wen-Hsiang" last="Chen">Wen-Hsiang Chen</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
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<placeName><region type="state">Texas</region>
</placeName>
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</placeName>
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</affiliation>
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<author><name sortKey="Tricoche, Nancy" sort="Tricoche, Nancy" uniqKey="Tricoche N" first="Nancy" last="Tricoche">Nancy Tricoche</name>
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<country>États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Lindsley F Kimball Research Institute; New York Blood Center; New York</wicri:cityArea>
</affiliation>
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<author><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology; University of Texas Medical Branch; Galveston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology; University of Texas Medical Branch; Galveston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Seid, Christopher A" sort="Seid, Christopher A" uniqKey="Seid C" first="Christopher A" last="Seid">Christopher A. Seid</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hudspeth, Elissa M" sort="Hudspeth, Elissa M" uniqKey="Hudspeth E" first="Elissa M" last="Hudspeth">Elissa M. Hudspeth</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lustigman, Sara" sort="Lustigman, Sara" uniqKey="Lustigman S" first="Sara" last="Lustigman">Sara Lustigman</name>
<affiliation wicri:level="2"><nlm:affiliation>Lindsley F Kimball Research Institute; New York Blood Center; New York, NY USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Lindsley F Kimball Research Institute; New York Blood Center; New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology; University of Texas Medical Branch; Galveston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology; University of Texas Medical Branch; Galveston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bottazzi, Maria Elena" sort="Bottazzi, Maria Elena" uniqKey="Bottazzi M" first="Maria Elena" last="Bottazzi">Maria Elena Bottazzi</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hotez, Peter J" sort="Hotez, Peter J" uniqKey="Hotez P" first="Peter J" last="Hotez">Peter J. Hotez</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zhan, Bin" sort="Zhan, Bin" uniqKey="Zhan B" first="Bin" last="Zhan">Bin Zhan</name>
<affiliation wicri:level="2"><nlm:affiliation>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston, TX USA.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; National School of Tropical Medicine; Baylor College of Medicine; Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F Kimball Research Institute; New York Blood Center; New York, NY USA; Key Laboratory of Medical Molecular Virology of MOE/MOH; Shanghai Medical College and Institute of Medical Microbiology; Fudan University; Shanghai, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Lindsley F Kimball Research Institute; New York Blood Center; New York, NY USA; Key Laboratory of Medical Molecular Virology of MOE/MOH; Shanghai Medical College and Institute of Medical Microbiology; Fudan University; Shanghai</wicri:regionArea>
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</affiliation>
</author>
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<idno type="eISSN">2164-554X</idno>
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<term>Alum Compounds (administration & dosage)</term>
<term>Animals</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Glycosylation</term>
<term>Mice, Inbred BALB C</term>
<term>Pichia (genetics)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (immunology)</term>
<term>SARS Virus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus (genetics)</term>
<term>Spike Glycoprotein, Coronavirus (immunology)</term>
<term>Vaccines, Synthetic (administration & dosage)</term>
<term>Vaccines, Synthetic (genetics)</term>
<term>Vaccines, Synthetic (immunology)</term>
<term>Viral Vaccines (administration & dosage)</term>
<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adjuvants immunologiques (administration et posologie)</term>
<term>Alun (administration et posologie)</term>
<term>Animaux</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (immunologie)</term>
<term>Glycosylation</term>
<term>Pichia (génétique)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Souris de lignée BALB C</term>
<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins antiviraux (génétique)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins synthétiques (administration et posologie)</term>
<term>Vaccins synthétiques (génétique)</term>
<term>Vaccins synthétiques (immunologie)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adjuvants, Immunologic</term>
<term>Alum Compounds</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Adjuvants immunologiques</term>
<term>Alun</term>
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Pichia</term>
<term>Recombinant Proteins</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
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<term>Protéines recombinantes</term>
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term>
<term>Protéines recombinantes</term>
<term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Recombinant Proteins</term>
<term>SARS Virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Glycosylation</term>
<term>Mice, Inbred BALB C</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Glycosylation</term>
<term>Souris de lignée BALB C</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development. </div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Texas</li>
<li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Texas"><name sortKey="Chen, Wen Hsiang" sort="Chen, Wen Hsiang" uniqKey="Chen W" first="Wen-Hsiang" last="Chen">Wen-Hsiang Chen</name>
</region>
<name sortKey="Bottazzi, Maria Elena" sort="Bottazzi, Maria Elena" uniqKey="Bottazzi M" first="Maria Elena" last="Bottazzi">Maria Elena Bottazzi</name>
<name sortKey="Chag, Shivali M" sort="Chag, Shivali M" uniqKey="Chag S" first="Shivali M" last="Chag">Shivali M. Chag</name>
<name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<name sortKey="Hotez, Peter J" sort="Hotez, Peter J" uniqKey="Hotez P" first="Peter J" last="Hotez">Peter J. Hotez</name>
<name sortKey="Hudspeth, Elissa M" sort="Hudspeth, Elissa M" uniqKey="Hudspeth E" first="Elissa M" last="Hudspeth">Elissa M. Hudspeth</name>
<name sortKey="Lustigman, Sara" sort="Lustigman, Sara" uniqKey="Lustigman S" first="Sara" last="Lustigman">Sara Lustigman</name>
<name sortKey="Ma, Cuiqing" sort="Ma, Cuiqing" uniqKey="Ma C" first="Cuiqing" last="Ma">Cuiqing Ma</name>
<name sortKey="Seid, Christopher A" sort="Seid, Christopher A" uniqKey="Seid C" first="Christopher A" last="Seid">Christopher A. Seid</name>
<name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name>
<name sortKey="Tricoche, Nancy" sort="Tricoche, Nancy" uniqKey="Tricoche N" first="Nancy" last="Tricoche">Nancy Tricoche</name>
<name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
<name sortKey="Zhan, Bin" sort="Zhan, Bin" uniqKey="Zhan B" first="Bin" last="Zhan">Bin Zhan</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

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