A universal TLR7-nanoparticle adjuvant promotes broad immune responses against heterologous strains of Influenza and SARS-CoV-2

Abstract Fully effective vaccines for viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple drifted virus strains. However, how to achieve a diverse response has no general solution except to combine multiple strains, which risks diluting the response for all strains included. Here, we describe the synthesis of a universal, toll-like receptor 7 agonist (TLR7)-nanoparticle adjuvant, TLR7-NP, constructed from TLR7 agonist-initiated ring-opening polymerization of lactide and self-assembly with poly(ethylene glycol)-b-poly(lactic-co-glycolic acid). When mixed with Alum-adsorbed antigens, this TLR7-NP adjuvant elicited cross-reactive antibodies for both dominant and subdominant epitopes, as well as antigen-specific CD8+ T cell responses. TLR7-NPs adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NPs also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of a virus-like response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.

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Hierarchical Self-Assembly of Microgel-Modified Biomaterials Surfaces

MRS Proceedings ◽

10.1557/opl.2014.399 ◽

2014 ◽

Vol 1622 ◽

pp. 1-6

Author(s):

Yong Wu ◽

Jing Liang ◽

Qichen Wang ◽

Matthew Libera

Keyword(s):

Self Assembly ◽

Scale Effects ◽

Control Surface ◽

Poly Ethylene Glycol ◽

Hydrogel Particles ◽

Network Properties ◽

Tissue Cells ◽

Poly Ethylene ◽

Non Line Of Sight

ABSTRACTMicrogels are hydrogel particles with micron and sub-micron diameters. They have beendeveloped, studied, and exploited for a broad range of applications because of their uniquecombination of size, soft mechanical properties, and controllable network properties. We havebeen using microgels to modulate the properties of surfaces to differentially control theirinteractions with tissue cells and bacteria. The long-term goal is to create biomaterials thatpromote healing while simultaneously inhibiting infection. Because poly(ethylene glycol) [PEG]is used in a number of FDA-approved products and has well-known antifouling properties, wework primarily with PEG-based microgels. We render these anionic either by copolymerizationwith monomeric acids or by blending with polyacids. Both methods produce pH-dependentnegative charge. Surfaces, both planar 2-D surfaces as well as topographically complex 3-Dsurfaces, can be modified using a hierarchy of non-line-of-sight electrostatic depositionprocesses that create biomaterials surfaces whose cell adhesiveness is modulated by a submonolayerof microgels. Average inter-microgel spacings of 1-2 microns exploit naturaldifferences between staphylococcal bacteria and tissue cells, which open the opportunity todifferentially control surface interactions with them based on length-scale effects. Afterdeposition, the microgels can be loaded with a variety of small-molecule, cationic antimicrobials.The details of loading depend on the relative sizes of the antimicrobials and the microgelnetwork structure as well as on the amount and spatial distribution of electrostatic charge withinboth the microgel and on the antimicrobial. The exposed surface between microgels can befurther modified by the adsorption of adhesion-promoting proteins such as fibronectin viaelectrostatic interaction. This approach combines a rich interplay of microgel structure andchemistry as a key component in a simple and translatable approach to modulate the surfaceproperties of next-generation biomaterials.

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Synthesis and self-assembly behaviour of poly(Nα-Boc-l-tryptophan)-block-poly(ethylene glycol)-block-poly(Nα-Boc-l-tryptophan)

RSC Advances ◽

10.1039/c6ra03718f ◽

2016 ◽

Vol 6 (29) ◽

pp. 24142-24153

Author(s):

Andreea S. Voda ◽

Kevin Magniez ◽

Nisa V. Salim ◽

Cynthia Wong ◽

Qipeng Guo

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Self Assembly ◽

Triblock Copolymers ◽

Potential Drug ◽

Poly Ethylene Glycol ◽

Drug Delivery Applications ◽

Poly Ethylene ◽

First Time

We report for the first time the use of Nα-Boc-l-tryptophan for the synthesis of amphiphilic BAB triblock copolymers for potential drug delivery applications.

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