A reverse vaccinology and immunoinformatics approach for designing a multiepitope vaccine against SARS-CoV-2 DOI Creative Commons
Ehsan Jahangirian,

Ghadir A. Jamal,

MohammadReza Nouroozi

et al.

Immunogenetics, Journal Year: 2021, Volume and Issue: 73(6), P. 459 - 477

Published: Sept. 20, 2021

Since 2019, the world was involved with SARS-CoV-2 and consequently, announcement by World Health Organization that COVID-19 a pandemic, scientific were an effort to obtain best approach combat this global dilemma. The way prevent pandemic from spreading further is use vaccine against COVID-19. Here, we report design of recombinant multi-epitope four proteins spike or crown (S), membrane (M), nucleocapsid (N), envelope (E) using immunoinformatics tools. We evaluated most antigenic epitopes bind HLA class 1 subtypes, along 2, as well B cell epitopes. Beta-defensin 3 PADRE sequence used adjuvants in structure vaccine. KK, GPGPG, AAY linkers fuse selected nucleotide cloned into pET26b(+) vector restriction enzymes XhoI NdeI, HisTag considered C-terminal construct. results showed proposed candidate 70.87 kDa protein high antigenicity immunogenicity non-allergenic non-toxic. A total 95% have conservancy similar sequences. Molecular docking strong binding between tool-like receptor (TLR) 7/8. docking, molecular dynamics, MM/PBSA analysis established stable interaction both structures TLR7 TLR8. Simulation immune stimulation it evokes responses related humoral cellular immunity.

Language: Английский

Mechanisms of SARS-CoV-2 entry into cells DOI Creative Commons
Cody B. Jackson, Michael Farzan, Bing Chen

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 3 - 20

Published: Oct. 5, 2021

Language: Английский

Citations

2511
SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters DOI Creative Commons
Peter Halfmann, Shun Iida, Kiyoko Iwatsuki‐Horimoto

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 687 - 692

Published: Jan. 21, 2022

The recent emergence of B.1.1.529, the Omicron variant

Language: Английский

Citations

599
Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants DOI Creative Commons
Sachin Bhagchandani,

Jeremiah A. Johnson,

Darrell J. Irvine

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 175, P. 113803 - 113803

Published: May 29, 2021

Imidazoquinoline derivatives (IMDs) and related compounds function as synthetic agonists of Toll-like receptors 7 8 (TLR7/8) one is FDA approved for topical antiviral skin cancer treatments. Nevertheless, these innate immune system-activating drugs have potentially much broader therapeutic utility; they been pursued antitumor immunomodulatory agents more recently candidate vaccine adjuvants infectious disease. The broad expression profiles TLR7/8, poor pharmacokinetic properties IMDs, toxicities associated with systemic administration, however, are formidable barriers to successful clinical translation. Herein, we review IMD formulations that advanced the clinic discuss issues biodistribution toxicity hampered further development compounds. Recent strategies aimed at enhancing safety efficacy, particularly through use bioconjugates nanoparticle alter pharmacokinetics, biodistribution, cellular targeting, described. Finally, key aspects biology TLR7 signaling, such tolerance, may need be considered in new therapeutics discussed.

Language: Английский

Citations

126
Bioorthogonal-Activated In Situ Vaccine Mediated by a COF-Based Catalytic Platform for Potent Cancer Immunotherapy DOI
Mengyu Sun, Zhengwei Liu, Li Wu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5330 - 5341

Published: Feb. 23, 2023

Personalized tumor vaccines have become a promising modality for cancer immunotherapy. However, in situ personalized generated from immunogenic cell death (ICD) and adjuvants are mired by toxic side effects unsatisfactory efficiency. Herein, functionalizing the reticular structure to optimize catalytic activity of materials, series biocompatible covalent organic framework (COF)-based catalysts been designed screened establishing bioorthogonal-activated vaccine an efficient safe way. Especially, pro-doxorubicin (pro-DOX) could be bioorthogonally activated COF-based Fe(II) catalysts, which elicited ICD released tumor-associated antigens (TAAs). This prodrug activation strategy minimize drug maximize treatment effects. More importantly, system also catalytically activate pro-imiquimod (pro-IMQ, TLR7/8 immune agonist), served as adjuvant amplify antitumor immunity. Notably, this not only facilitated strong response but prevented dose-dependent chemotherapeutic drugs, including systemic inflammation caused random distribution adjuvants. To best our knowledge, it is first time devise platform generating vaccine, would provide paradigm achieving secure robust

Language: Английский

Citations

84
Sterilizing Immunity against SARS‐CoV‐2 Infection in Mice by a Single‐Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist‐Adjuvanted Recombinant Spike Protein Vaccine** DOI Open Access
Sonia Jangra,

Jana De Vrieze,

Angela Choi

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(17), P. 9467 - 9473

Published: Jan. 19, 2021

Abstract The search for vaccines that protect from severe morbidity and mortality because of infection with acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causes disease 2019 (COVID‐19) is a race against clock virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting conjugated to chain end cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It water‐soluble exhibits massive translocation lymph nodes upon local administration through binding albumin, affording localized innate immune activation reduction in systemic inflammation. adjuvanticity IMDQ‐PEG‐CHOL was validated licensed vaccine setting (quadrivalent influenza vaccine) experimental trimeric recombinant SARS‐CoV‐2 spike protein vaccine, showing robust IgG2a IgG1 antibody titers mice could neutralize viral vitro vivo mouse model.

Language: Английский

Citations

63
A defective viral genome strategy elicits broad protective immunity against respiratory viruses DOI Creative Commons
Yinghong Xiao, Peter V. Lidsky, Yuta Shirogane

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(25), P. 6037 - 6051.e14

Published: Nov. 18, 2021

Language: Английский

Citations

60
In Situ Polymerization-Mediated Antigen Presentation DOI
Chao Pan, Lu Wang, Mengmeng Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(24), P. 13261 - 13272

Published: June 1, 2023

Activating antigen-presenting cells is essential to generate adaptive immunity, while the efficacy of conventional activation strategies remains unsatisfactory due suboptimal antigen-specific priming. Here, in situ polymerization-mediated antigen presentation (IPAP) described, which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto surface dendritic vivo through co-deposition with dopamine. The resulting chemically bound can promote by elevating macropinocytosis-based cell uptake reducing lysosome-related degradation. IPAP able prolong duration reservation injection site enhance subsequent accumulation draining lymph nodes, thereby eliciting robust cellular humoral immune responses. also applicable for different antigens capable circumventing disadvantages complicated preparation purification. By implementation ovalbumin, induces a significant protective immunity against ovalbumin-overexpressing tumor challenge prophylactic murine model. use SARS-CoV-2 Spike protein S1 subunit remarkably increases production S1-specific immunoglobulin G mice. offers unique strategy stimulating boost responses proposes facile yet versatile method immunization various diseases.

Language: Английский

Citations

29
In situ cellular hitchhiking of nanoparticles for drug delivery DOI Creative Commons
Edidiong Udofa, Zongmin Zhao

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 204, P. 115143 - 115143

Published: Nov. 24, 2023

Language: Английский

Citations

28
Impact of FcRn antagonism on vaccine-induced protective immune responses against viral challenge in COVID-19 and influenza mouse vaccination models DOI Creative Commons
Prajakta Warang, Gagandeep Singh,

Mahan Moshir

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: March 3, 2025

Antagonism of the neonatal Fc receptor through an engineered antibody fragment, such as efgartigimod, results in a decrease immunoglobulin G levels. This approach is being evaluated therapeutic strategy for treatment IgG-mediated autoimmune diseases. Our goal was to evaluate impact mFc-ABDEG, mouse-adapted fragment with mode action highly similar on vaccine-induced protective immune responses against viral infections. Therefore, mouse vaccination models COVID-19 and influenza were employed, utilizing mRNA vaccine (COMIRNATY) adjuvanted, inactivated quadrivalent (Seqirus+AddaVax), respectively. In both models, induced robust humoral responses. As expected, animals treated mFc-ABDEG had lower levels virus-specific IgG, while IgM remained unaffected. The strong Th1-type T cell response irrespective treatment. Influenza resulted poor induction, regardless treatment, due Th2-biased that vaccines typically induce. Importantly, no effect immunity live challenges models. Vaccinated equally protected non-treated vaccinated controls. These non-clinical data demonstrate FcRn antagonism did not affect generation cellular responses, or protection challenges. substantiate clinical observations that, although IgG titers reduced, efgartigimod impair ability generate new specific timing vaccination.

Language: Английский

Citations

1
Self-Adjuvanting Lipoprotein Conjugate αGalCer-RBD Induces Potent Immunity against SARS-CoV-2 and its Variants of Concern DOI
Jian Wang, Yu Wen, Shihao Zhou

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(3), P. 2558 - 2570

Published: Jan. 24, 2022

Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) its variants are the best approach to successfully combat COVID-19 pandemic. The receptor-binding domain (RBD) of viral spike protein is a major target develop candidate vaccines. α-Galactosylceramide (αGalCer), potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated

Language: Английский

Citations

35