Controlling timing and location in vaccines

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 158, P. 91 - 115

Published: Jan. 1, 2020

Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation T B cells in lymph nodes. Among many parameters impacting resulting response, presence antigen inflammatory cues for an temporal duration within nodes, further subcompartments nodes– right timing location– play a critical role shaping cellular humoral immunity. Here we review recent advances our understanding how vaccine kinetics biodistribution impact immunity, underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer properties future vaccines, with focus on subunit vaccines.

Language: Английский

---

Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

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

---

Targeted modulation of immune cells and tissues using engineered biomaterials

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(2), P. 107 - 124

Published: Jan. 30, 2023

Language: Английский

---

Chemical Strategies to Boost Cancer Vaccines

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(20), P. 11420 - 11478

Published: Sept. 11, 2020

Personalized cancer vaccines (PCVs) are reinvigorating vaccine strategies in immunotherapy. In contrast to adoptive T-cell therapy and checkpoint blockade, the PCV strategy modulates innate adaptive immune systems with broader activation redeploy antitumor immunity individualized tumor-specific antigens (neoantigens). Following a sequential scheme of tumor biopsy, mutation analysis, epitope prediction, administration neoantigens synthetic long peptide (SLP) or mRNA formulations dramatically improves population activity antigen-specific CD4+ CD8+ T cells. Despite promising prospect PCVs, there is still great potential for optimizing prevaccination procedures potency. particular, arduous development tumor-associated antigen (TAA)-based provides valuable experience rational principles augmenting potency which expected advance through design adjuvants, delivery systems, immunosuppressive microenvironment (TME) reversion since current personalized vaccination simply admixes adjuvants. Considering application TAA-based design, these two complement each other can lead both universal therapeutic methods. Chemical provide vast opportunities (1) exploring novel including molecules materials optimizable activity, (2) constructing efficient precise avoid systemic diffusion, improve biosafety, target secondary lymphoid organs, enhance presentation, (3) combining bioengineering methods innovate improvements conventional vaccination, "smartly" re-educate TME, modulate immunity. As chemical have proven versatility, reliability, universality cell- B cell-based vaccines, union such numerous construction new vigor vitality treatment.

Language: Английский

---

Engineering Strategies for Lymph Node Targeted Immune Activation

Accounts of Chemical Research, Journal Year: 2020, Volume and Issue: 53(10), P. 2055 - 2067

Published: Sept. 10, 2020

ConspectusDevelopment of vaccine technology that induces long lasting and potent adaptive immune responses is vital importance to combat emerging pathogens design the next generation cancer immunotherapies. Advanced biomaterials such as nanoparticle carriers are intensively explored increase efficacy safety vaccines immunotherapies, based on their intrinsic potential focus therapeutic payload onto relevant cells limit systemic distribution. With being primarily initiated in lymph nodes, potency turn tightly linked capacity reach accumulate nodes draining immunization site. Here, we discuss main strategies applied delivery nodes: (1) direct node injection, (2) active cell-mediated transport through targeting peripheral dendritic cells, (3) exploiting passive afferent lymphatics.The intralymph nodal injection obviously most way for nanoparticles multiple studies have demonstrated its capability enhancing immunostimulant drugs' activation increasing window. However, requirement using ultrasound guidance mapping patients renders intranodal administration unsuited mass vaccination campaigns. As fine structured organs with lymphocytes chemokine gradients arrayed a highly ordered fashion, breakdown formats by another concern. The exploitation live vectors transporting has been studied both ex vivo vivo. While engineering theory can achieve 100% cell-specific selectivity, scenario impossible be achieved vivo, this procedure usually laborious complicated entails participation professional staff equipment. In addition, poor efficiency cell migration significant limitation following cultured cells. Thus, surface receptors, particularly C-type lectin conjugating antibodies or ligands academia industry. Although still face nonspecific engulfment various phagocytes, shown feasibility high selectivity. Moreover, optimizing physicochemical properties nanoparticles, passively drain carried interstitial flow. Compared transport, much faster higher efficiency. Of all properties, size important parameter large particles (>500 nm) only an transport. Other charge balance hydrophobicity-vs-hydrophilicity, strongly influence mobility extracellular space. albumin, natural fatty acid transporter, recently capable binding amphiphiles lipid moiety subsequent them nodes.

Language: Английский

---

Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(28), P. 12133 - 12139

Published: June 11, 2020

Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from site injection into systemic circulation. Here, we report on design and synthesis an amphiphilic polymer-prodrug conjugate imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures 200 nm. The contains endosomal enzyme-responsive linker enabling degradation vesicles release native form after endocytosis, which results high vitro TLR activity. In a mouse model, locally administered provoke significantly more long-lasting immune stimulation terms interferon expression at draining lymphoid tissue compared nonamphiphilic control agonist. Moreover, robust activation dendritic lymph node vivo.

Language: Английский

---

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**

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

---

Azide‐Masked Resiquimod Activated by Hypoxia for Selective Tumor Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(29)

Published: April 22, 2023

Resiquimod (R848) is an immunomodulator that causes a severe systemic inflammatory reaction due to low tumor selectivity, thus hindering its use in cancer therapy. Therefore, azide-masked prodrug (R848-N3 ) of R848 developed, which selectively activated hypoxic tumors. R848-N3 significantly reduces pro-inflammatory cytokines treated mice 1/12 compared at the same dose. In addition, combretastatin A4 nanoparticles (CA4-NPs) are used enhance selectivity by elevating level hypoxia. +CA4-NPs has higher than intratumoral injection 1 h after administration. The concentration active 21.45-fold heart. Benefiting from high , +CA4-NPs+anti-PD1 exerted 94.1% suppression and 40.0% cure. this work highlights potential azide-masking strategy development tumor-selective prodrugs with reduced toxicity.

Language: Английский

---

In situ cellular hitchhiking of nanoparticles for drug delivery

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

Published: Nov. 24, 2023

Language: Английский

---

Current Status of COVID‐19 (Pre)Clinical Vaccine Development

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(43), P. 18885 - 18897

Published: July 14, 2020

Abstract The current COVID‐19 pandemic has a tremendous impact on daily life world‐wide. Despite the ability to dampen spread of SARS‐CoV‐2, causative agent diseases, through restrictive interventions, it is believed that only effective vaccines will provide sufficient control over disease and revert societal live back normal. At present, double‐digit number efforts are devoted development vaccine against COVID‐19. Here, we an overview these (pre)clinical background information technologies behind vaccines. In addition, discuss potential hurdles need be addressed prior mass scale clinical translation successful candidates.

Language: Английский

---