Chemical Synthesis Creates Single Glycoforms of the Ectodomain of Herpes Simplex Virus-1 Glycoprotein D DOI
Jie Zhao, Xinliang Liu, Jialin Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(4), P. 2615 - 2623

Published: Dec. 20, 2023

Herpes simplex virus-1 (HSV-1) utilizes multiple viral surface glycoproteins to trigger virus entry and fusion. Among these glycoproteins, glycoprotein D (gD) functions as a receptor-binding protein, which makes it an attractive target for the development of vaccines against HSV-1 infection. Several recombinant gD subunit have been investigated in both preclinical clinical phases with varying degrees success. It is fundamentally critical explore glycans. In light this, we report efficient synthetic platform construct glycosylated gDs bearing homogeneous glycans at N94 N121. The oligosaccharides were prepared by enzymatic synthesis conjugated peptidyl sectors. constructed via combination 7-(piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ)-assisted expressed protein ligation β-mercapto amino acid-assisted-desulfurization strategies. Biological studies showed that exhibited potent vivo activity mice.

Language: Английский

Distinct core glycan and O-glycoform utilization of SARS-CoV-2 Omicron variant Spike protein RBD revealed by top-down mass spectrometry DOI Creative Commons
David S. Roberts, Morgan Mann, Brad H. Li

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(36), P. 10944 - 10949

Published: Jan. 1, 2022

Top-down mass spectrometry reveals O -glycoform structural changes in the SARS-CoV-2 Omicron variant. Resolving mutations and post-translational alterations can inform strategies for designing variant-directed diagnostics therapeutics.

Language: Английский

Citations

23
Novel sialoglycan linkage for constructing adjuvant-protein conjugate as potent vaccine for COVID-19 DOI Open Access
Yu Wen, Ruyan Zhang, Jian Wang

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 355, P. 238 - 247

Published: Feb. 8, 2023

Language: Английский

Citations

15
Precision-engineering of subunit vaccine particles for prevention of infectious diseases DOI Creative Commons
Shuxiong Chen, Saranya Pounraj,

Nivethika Sivakumaran

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 3, 2023

Vaccines remain the best approach for prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell but often show reduced immunogenicity. Subunit in particulate format improved vaccine efficacy by inducing strong immune responses leading protective immunity against respective pathogens. Antigens with proper conformation and function required induce functional responses. Production such antigens requiring post-translational modifications and/or composed multiple complex domains bacterial hosts remains challenging. Here, we discuss strategies overcome these limitations toward development eliciting desired humoral cellular We also describe innovative concepts assembling candidates bearing modifications. The approaches include non-covalent attachments (e.g. biotin-avidin affinity) covalent SpyCatcher-SpyTag) attach post-translationally modified particles.

Language: Английский

Citations

15
Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5 DOI Creative Commons
Brian Imbiakha,

Shahrzad Ezzatpour,

David W. Buchholz

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(38)

Published: Sept. 22, 2023

Pathology studies of SARS-CoV-2 Omicron variants concern (VOC) are challenged by the lack pathogenic animal models. While BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity mortality, less is known about more recent VOC. Here, we show that contrast BA.1, BA.5-infected mice exhibited high levels correlating with higher early viral loads. Neither nor BA.5 replicated brains, unlike most prior Only BA.5–infected substantial weight loss, pathology scores lungs, inflammatory cells cytokines bronchoalveolar lavage fluid, 5- 8-month-old 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure circulating BA.5. Further, differences mortality between provide understanding determinants pathogenicity.

Language: Английский

Citations

13
Chemical Synthesis Creates Single Glycoforms of the Ectodomain of Herpes Simplex Virus-1 Glycoprotein D DOI
Jie Zhao, Xinliang Liu, Jialin Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(4), P. 2615 - 2623

Published: Dec. 20, 2023

Herpes simplex virus-1 (HSV-1) utilizes multiple viral surface glycoproteins to trigger virus entry and fusion. Among these glycoproteins, glycoprotein D (gD) functions as a receptor-binding protein, which makes it an attractive target for the development of vaccines against HSV-1 infection. Several recombinant gD subunit have been investigated in both preclinical clinical phases with varying degrees success. It is fundamentally critical explore glycans. In light this, we report efficient synthetic platform construct glycosylated gDs bearing homogeneous glycans at N94 N121. The oligosaccharides were prepared by enzymatic synthesis conjugated peptidyl sectors. constructed via combination 7-(piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ)-assisted expressed protein ligation β-mercapto amino acid-assisted-desulfurization strategies. Biological studies showed that exhibited potent vivo activity mice.

Language: Английский

Citations

13