Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments--the importance of immunofocusing in subunit vaccine design.
Identifieur interne : 001846 ( PubMed/Curation ); précédent : 001845; suivant : 001847Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments--the importance of immunofocusing in subunit vaccine design.
Auteurs : Cuiqing Ma [États-Unis] ; Lili Wang [États-Unis] ; Xinrong Tao [États-Unis] ; Naru Zhang [États-Unis] ; Yang Yang [États-Unis] ; Chien-Te K. Tseng [États-Unis] ; Fang Li [États-Unis] ; Yusen Zhou [République populaire de Chine] ; Shibo Jiang [États-Unis] ; Lanying Du [États-Unis]Source :
- Vaccine [ 1873-2518 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (sang), Anticorps neutralisants (sang), Antigènes viraux (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Fragments Fc des immunoglobulines (immunologie), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Immunoglobuline G (sang), Infections à coronavirus (), Lapins, Récepteurs viraux (métabolisme), Souris de lignée BALB C, Tests de neutralisation, Vaccins antiviraux (immunologie), Vaccins sous-unitaires (immunologie).
- MESH :
- immunologie : Antigènes viraux, Fragments Fc des immunoglobulines, Glycoprotéine de spicule des coronavirus, Vaccins antiviraux, Vaccins sous-unitaires.
- métabolisme : Récepteurs viraux.
- sang : Anticorps antiviraux, Anticorps neutralisants, Immunoglobuline G.
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Humains, Infections à coronavirus, Lapins, Souris de lignée BALB C, Tests de neutralisation.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Antigens, Viral (immunology), Coronavirus Infections (prevention & control), Female, Humans, Immunoglobulin Fc Fragments (immunology), Immunoglobulin G (blood), Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus, Neutralization Tests, Rabbits, Receptors, Virus (metabolism), Spike Glycoprotein, Coronavirus (immunology), Vaccines, Subunit (immunology), Viral Vaccines (immunology).
- MESH :
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G.
- chemical , immunology : Antigens, Viral, Immunoglobulin Fc Fragments, Spike Glycoprotein, Coronavirus, Vaccines, Subunit, Viral Vaccines.
- chemical , metabolism : Receptors, Virus.
- prevention & control : Coronavirus Infections.
- Animals, Female, Humans, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus, Neutralization Tests, Rabbits.
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".
DOI: 10.1016/j.vaccine.2014.08.086
PubMed: 25240756
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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>
</front>
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<Abstract><AbstractText>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". </AbstractText>
<CopyrightInformation>Copyright © 2014 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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