Gold nanoparticle‐adjuvanted S protein induces a strong antigen‐specific IgG response against severe acute respiratory syndrome‐related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs

Sekimukai, Hanako; Iwata‐Yoshikawa, Naoko; Fukushi, Shuetsu; Tani, Hideki; Kataoka, Michiyo; Suzuki, Tadaki; Hasegawa, Hideki; Niikura, Kenichi; Arai, Katsuhiko; Nagata, Noriyo

doi:10.1111/1348-0421.12754

Cited by 150 publications

(171 citation statements)

References 71 publications

(107 reference statements)

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“…Spike protein has also been the focus for vaccine development. For example, mice vaccinated with DNA or subunit vaccines composed of spike proteins (or receptor-binding domain of spike proteins) and adjuvants had high titers of immunoglobulin G antibodies and were protected from SARS-CoV-1 or Middle East respiratory syndrome coronavirus infection (Du et al 2010, Du et al 2007, Honda-Okubo et al 2015, Iwata-Yoshikawa et al 2014, Li et al 2013, Lu et al 2010, Sekimukai et al 2020, Yang et al 2004, Zhao et al 2014. Toll-like receptor ligands, delta inulin, and monophosphoryl lipid A were reported as effective adjuvants to be combined with subunit vaccines.…”

Section: Discussionmentioning

confidence: 99%

Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics

Zhou

Tian

et al. 2020

Glycobiology

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Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell-derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1-4 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes: a minimal length of peptide is first clamped by a paratope and sugar modifications close to the peptide either strengthen or do not hinder the binding.

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Section: Discussionmentioning

confidence: 99%

Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics

Zhou

Tian

et al. 2020

Glycobiology

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“…Spike protein has also been the focus for vaccine development (20). High titers of IgG antibodies were reported to protect mice from SARS-CoV or MERS-CoV viral infection in mice vaccinated by DNA or subunit vaccines composed by Spike proteins (or RBD of Spike proteins) and adjuvants (21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Identification of 22 N-glycosites on Spike Glycoprotein of SARS-CoV-2 and Accessible Surface Glycopeptide Motifs: Implications on Vaccination and Antibody Therapeutics

Zhou¹,

Qi²,

Wen³

et al. 2020

Preprint

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Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed recombinant SARS-CoV-2 Spike protein secreted from BTI-Tn-5B1-4 cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired MS/MS spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of Spike proteins according to Cryo-EM and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. The results showed that all 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose type of N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the Spike receptor binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV-1, and 985 to 1034 of SARS-CoV-2 Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.

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“…a comparison with a commercial whole inactivated viral vaccine also showed that the GNP conjugate provided better antiviral protection. GNPs conjugated to the S protein of severe acute respiratory syndrome-related coronavirus induced a strong IgG response upon immunization of mice [114].…”

Section: Article Highlightsmentioning

confidence: 99%

Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases

Дыкман

2020

Expert Review of Vaccines

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Introduction: Vaccination remains very effective in stimulating protective immune responses against infections. An important task in antibody and vaccine preparation is to choose an optimal carrier that will ensure a high immune response. Particularly promising in this regard are nanoscale particle carriers. An antigen that is adsorbed or encapsulated by nanoparticles can be used as an adjuvant to optimize the immune response during vaccination. a very popular antigen carrier used for immunization and vaccination is gold nanoparticles, with are being used to make new vaccines against viral, bacterial, and parasitic infections. Areas covered: This review summarizes what is currently known about the use of gold nanoparticles as an antigen carrier and adjuvant to prepare antibodies in vivo and design vaccines against viral, bacterial, and parasitic infections. The basic principles, recent advances, and current problems in the use of gold nanoparticles are discussed. Expert opinion: Gold nanoparticles can be used as adjuvants to increase the effectiveness of vaccines by stimulating antigen-presenting cells and ensuring controlled antigen release. Studying the characteristics of the immune response obtained from the use of gold nanoparticles as a carrier and an adjuvant will permit the particles' potential for vaccine design to be increased.

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Gold nanoparticle‐adjuvanted S protein induces a strong antigen‐specific IgG response against severe acute respiratory syndrome‐related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs

Cited by 150 publications

References 71 publications

Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics

Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics

Identification of 22 N-glycosites on Spike Glycoprotein of SARS-CoV-2 and Accessible Surface Glycopeptide Motifs: Implications on Vaccination and Antibody Therapeutics

Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases

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