Recent advances in chemical protein synthesis: method developments and biological applications

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 1060 - 1096

Published: March 12, 2024

Language: Английский

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Advances in Polymer‐Based Self‐Adjuvanted Nanovaccines

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Nanovaccines, as a new generation of vaccines, have garnered significant interest due to their exceptional potential in enhancing disease prevention and treatment. Their unique features, such high stability, antigens protection, prolonged retention, targeted delivery lymph nodes, immune cells, tumors, set them apart promising candidates the field immunotherapy. Polymers, with superior degradability, capacity mimic pathogen characteristics, surface functionality that facilitates modifications, serve ideal carriers for vaccine components. Polymer‐based self‐adjuvanted nanovaccines remarkable ability augment responses. The inherent adjuvant‐like properties polymers themselves offer pathway toward more efficient exploitation nanomaterials optimization nanovaccines. This review article aims summarize categorization elucidate mechanisms action adjuvants. Additionally, it delves into advantages limitations polymer‐based management prevention, providing valuable insights design application. comprehensive analysis could contribute development effective tailored wide range diseases.

Language: Английский

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pH-Sensitive and Biodegradable Mn₃(PO₄)₂·3H₂O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(7), P. 8914 - 8926

Published: Feb. 7, 2023

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of significance to enhance vaccine efficacy. In this work, we prepared long-term stable, pH-sensitive, biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution the first time employed it as an stimulant in bivalent COVID-19 protein comprised wild-type S1 (S1-WT) Omicron (S1-Omicron) proteins antigens elicit broad-spectrum immunity. The biological experiments indicated that nano-MnP could effectively activate antigen-presenting cells through cGAS–STING pathway. Compared conventional Alum-adjuvanted group, nano-MnP-adjuvanted elicited approximately 7- 8-fold increases IgG antibody titers antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera group cross-neutralize SARS-CoV-2 its five variants concern (VOCs) including Alpha, Beta, Gamma, Delta, Omicron, demonstrating based on S1-WT S1-Omicron effective design strategy induce responses. Collectively, material may provide efficient platform various prophylactic therapeutic vaccines insights development next-generation manganese adjuvant.

Language: Английский

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Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6822 - 6838

Published: April 8, 2024

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as carrier, in TLR1/2 agonist Pam3CSK4 was conjugated to N-terminus MUC1-loaded carrier BSA through pyridoxal 5′-phosphate-mediated transamination reaction. The resulting Pam3CSK4–BSA-MUC1 conjugate subsequently incorporated into liposomes, biomimics membrane structure tumor cells. results indicated that this significantly enhanced antigen uptake APCs and obviously augmented retention vaccine at injection site. Compared with BSA-MUC1 + groups, evoked 22- 11-fold increases MUC1-specific IgG titers. Importantly, elicited robust cellular immunity inhibited growth. This is first time constructed enhance immunogenicity, universal platform exhibits promise for utilization various vaccines, holding potential further clinical application.

Language: Английский

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Rationally Designed Highly Potent NKT Cell Agonists with Different Cytokine Selectivity through Hydrogen-Bond Interaction

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(15), P. 12819 - 12834

Published: July 20, 2024

Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy adjuvant development. However, identifying new potent NKT agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds intensify glycolipid/CD1d interaction. Two compounds

Language: Английский

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The Application of Biomaterials for the Vaccine, Treatment, and Detection of SARS-CoV-2

ACS Omega, Journal Year: 2024, Volume and Issue: 9(5), P. 5175 - 5192

Published: Jan. 26, 2024

The coronavirus disease-19 (COVID-19) pandemic has had a significant impact on human life worldwide since 2019. Specific vaccines and antiviral agents are the most effective means of preventing treating severe acute respiratory syndrome 2 (SARS-CoV-2) infections. Additionally, protective equipment early diagnosis also contribute to controlling spread COVID-19. utilization biomaterials in medicine pharmaceuticals is crucial ensure positive vaccines, agents, equipment. In this review, we discuss application various types biomaterials, including polymers, lipid nanoparticles, inorganic protein- or peptide-associated self-assembled other for vaccine, treatment, prevention Finally, provide perspective future opportunities challenges developing combat viral outbreaks diseases.

Language: Английский

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Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134620 - 134620

Published: Aug. 9, 2024

Language: Английский

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Influence of component structural arrangement on cholesterol-antigen conjugate immunogenicity and antisera bactericidal activity against group A Streptococcus

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 157, P. 108248 - 108248

Published: Feb. 6, 2025

Immune stimulants (adjuvants) are essential vaccine components; however, clinically approved adjuvants limited with the majority being derived from pathogenic components. In this study, adjuvanting capacity of cholesterol, a natural human lipid, was explored following conjugation peptide antigens. A structure-activity relationship study conducted to compare linear and branched cholesterol conjugates other lipopeptide vaccines commercial adjuvants. Group Streptococcus (GAS) M protein-derived J8 B-cell epitope universal helper T-cell P25 were selected as an antigen. addition, liposomal formulations cholesterol-based also evaluated in mouse model. Following subcutaneous intranasal administration, comprised induced highest antibody production. Linear triggered strong responses that killed GAS clinical isolates effectively by The immunogenicity greatly influenced structural arrangement conjugate lead self-adjuvanting desired immune response without any exogenous stimulation.

Language: Английский

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Adjuvant-Free COVID-19 Vaccine with Glycoprotein Antigen Oxidized by Periodate Rapidly Elicits Potent Immune Responses

ACS Chemical Biology, Journal Year: 2023, Volume and Issue: 18(4), P. 915 - 923

Published: April 3, 2023

Modification of antigens to improve their immunogenicity represents a promising direction for the development protein vaccine. Here, we designed facilely prepared adjuvant-free vaccines in which N-glycan SARS-CoV-2 receptor-binding domain (RBD) glycoprotein was oxidized by sodium periodate. This strategy only minimally modifies glycans and does not interfere with epitope peptides. The RBD high concentrations periodate (RBDHO) significantly enhanced antigen uptake mediated scavenger receptors promoted activation antigen-presenting cells. Without any external adjuvant, two doses RBDHO elicited 324- 27-fold increases IgG antibody titers neutralizing titers, respectively, compared unmodified antigen. Meanwhile, vaccine could cross-neutralize all variants concern. In addition, effectively cellular immune responses. study provides new insight vaccines.

Language: Английский

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Transcriptome-wide analyses of early immune responses in lumpfish leukocytes upon stimulation with poly(I:C)

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

Published: June 14, 2023

Background Both bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish ( Cyclopterus lumpus L.) poorly understood, leukocytes were stimulated with poly(I:C), synthetic analog of double stranded RNA, which mimic infections, RNA sequencing was performed. Methods To address this gap, we poly(I:C) for 6 24 hours did three parallels per timepoint. Genome guided mapping performed define differentially expressed genes (DEGs). Results Immune identified, transcriptome-wide analyses early responses showed that 376 2372 transcripts significantly post exposure (hpe) respectively. The most enriched GO terms when time had been accounted for, system processes (GO:0002376) response (GO:0006955). Analysis DEGs among highly upregulated TLRs belonging RIG-I signaling pathway, including LGP2, STING MX, as well IRF3 IL12A. not but silico encoding proteins involved pathogen recognition, cell signaling, cytokines TLR pathway mostly conserved compared mammals other teleost species. Conclusions Our unravel innate pathways playing role defense lumpfish. information gathered can be used comparative studies lay groundwork future functional pathogenicity mechanisms. Such knowledge is also necessary development immunoprophylactic measures lumpfish, extensively cultivated use cleaner fish aquaculture removal sea lice from Atlantic salmon Salmo salar L.).

Language: Английский

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