MersV1, PascalFrancis, Corpus, bibRecord, 000005

Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design

Identifieur interne : 000005 ( PascalFrancis/Corpus ); précédent : 000004; suivant : 000006

Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design

Auteurs : CUIQING MA ; LILI WANG ; XINRONG TAO ; NARU ZHANG ; YANG YANG ; Chien-Te K. Tseng ; FANG LI ; YUSEN ZHOU ; SHIBO JIANG ; LANYING DU

Source :

Vaccine [ 0264-410X ] ; 2014.

RBID : Pascal:14-0254916

Descripteurs français

Pascal (Inist)
- Coronavirus, Vaccin, Sousunité, Protéine.

English descriptors

KwdEn :
- Coronavirus, Protein, Subunit, Vaccine.

Abstract

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A11	`01`	`1`		`@1 CUIQING MA`
A11	`02`	`1`		`@1 LILI WANG`
A11	`03`	`1`		`@1 XINRONG TAO`
A11	`04`	`1`		`@1 NARU ZHANG`
A11	`05`	`1`		`@1 YANG YANG`
A11	`06`	`1`		`@1 TSENG (Chien-Te K.)`
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A14	`02`			`@1 Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch @2 Galveston, TX @3 USA @Z 3 aut. @Z 6 aut.`
A14	`03`			`@1 Department of Pharmacology, University of Minnesota Medical School @2 Minneapolis, MN @3 USA @Z 5 aut. @Z 7 aut.`
A14	`04`			`@1 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology @2 Beijing @3 CHN @Z 8 aut.`
A14	`05`			`@1 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University @2 Shanghai @3 CHN @Z 9 aut.`
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C01	`01`		`ENG`	@0 The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".
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Format Inist (serveur)

NO :	PASCAL 14-0254916 INIST
ET :	Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design
AU :	CUIQING MA; LILI WANG; XINRONG TAO; NARU ZHANG; YANG YANG; TSENG (Chien-Te K.); FANG LI; YUSEN ZHOU; SHIBO JIANG; LANYING DU
AF :	Lindsley F. Kimball Research Institute, New York Blood Center/New York, NY/Etats-Unis (1 aut., 2 aut., 4 aut., 9 aut., 10 aut.); Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch/Galveston, TX/Etats-Unis (3 aut., 6 aut.); Department of Pharmacology, University of Minnesota Medical School/Minneapolis, MN/Etats-Unis (5 aut., 7 aut.); State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology/Beijing/Chine (8 aut.); Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University/Shanghai/Chine (9 aut.)
DT :	Publication en série; Niveau analytique
SO :	Vaccine; ISSN 0264-410X; Coden VACCDE; Royaume-Uni; Da. 2014; Vol. 32; No. 46; Pp. 6170-6176; Bibl. 55 ref.
LA :	Anglais
EA :	The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".
CC :	002A05F04; 002A05C10
FD :	Coronavirus; Vaccin; Sousunité; Protéine
FG :	Coronaviridae; Nidovirales; Virus
ED :	Coronavirus; Vaccine; Subunit; Protein
EG :	Coronaviridae; Nidovirales; Virus
SD :	Coronavirus; Vacuna; Subunitad; Proteína
LO :	INIST-20289.354000502659590210
ID :	14-0254916

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Pascal:14-0254916

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<front><div type="abstract" xml:lang="en">The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".</div>
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<fA08 i1="01" i2="1" l="ENG"><s1>Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design</s1>
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<fA14 i1="01"><s1>Lindsley F. Kimball Research Institute, New York Blood Center</s1>
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<sZ>9 aut.</sZ>
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<fA14 i1="02"><s1>Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch</s1>
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<sZ>3 aut.</sZ>
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<fA14 i1="03"><s1>Department of Pharmacology, University of Minnesota Medical School</s1>
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<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
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<fA14 i1="04"><s1>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology</s1>
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<fA14 i1="05"><s1>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University</s1>
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<fC01 i1="01" l="ENG"><s0>The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".</s0>
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<server><NO>PASCAL 14-0254916 INIST</NO>
<ET>Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design</ET>
<AU>CUIQING MA; LILI WANG; XINRONG TAO; NARU ZHANG; YANG YANG; TSENG (Chien-Te K.); FANG LI; YUSEN ZHOU; SHIBO JIANG; LANYING DU</AU>
<AF>Lindsley F. Kimball Research Institute, New York Blood Center/New York, NY/Etats-Unis (1 aut., 2 aut., 4 aut., 9 aut., 10 aut.); Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch/Galveston, TX/Etats-Unis (3 aut., 6 aut.); Department of Pharmacology, University of Minnesota Medical School/Minneapolis, MN/Etats-Unis (5 aut., 7 aut.); State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology/Beijing/Chine (8 aut.); Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University/Shanghai/Chine (9 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Vaccine; ISSN 0264-410X; Coden VACCDE; Royaume-Uni; Da. 2014; Vol. 32; No. 46; Pp. 6170-6176; Bibl. 55 ref.</SO>
<LA>Anglais</LA>
<EA>The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".</EA>
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Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design

Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments-The importance of immunofocusing in subunit vaccine design

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