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

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

PROVIDER: PRJNA901401 | ENA |

REPOSITORIES: ENA

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

Project description:Effective vaccines against viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple variant virus strains. However, antibody responses to current vaccines often lack cross-reactivity due to immunodominance. Here, we describe the synthesis of a 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). TLR7-NP can enhance lymph node targeting, leading to persistent activation of immune cells. 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, in mice. TLR7-NP adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NP also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of an antiviral response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.

2022-11-14 | GSE217918 | GEO

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.

Project description:The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

| S-EPMC9981462 | biostudies-literature

Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

Project description:Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

| PRJNA857001 | ENA

Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

Project description:RNA sequencing was performed to identify immune-related genes that were differentially expressed in porcine monocyte-derived dendritic cells following stimulation with a novel phytoglycogen-based nanoparticle (Nano-11) and the TLR3 agonist poly(I:C).

2022-08-12 | GSE207745 | GEO

BCR repertoire analysis by Next-generation sequencing of lymphocytes harvested from mice vaccinated with liposomal TLR4 and TLR7 agonists

Project description:BALB/c mice were vaccinated with inactivated influenza A virus adjuvanted with liposomal TLR4 (2B182C) and TLR7 agonists (2B182C) on days 0 and 21. To examine whether the liposomal combined adjuvant increase BCR diversity, lymphocytes in the draining lymph nodes harvested on day 28 were analyzed using next-generation RNA sequencing technology.

2021-03-01 | E-MTAB-8870 | biostudies-arrayexpress

Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells

Project description:Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-g+ Th1 response in a TLR7 agonist dose-dependent manner. Single cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.

2023-11-17 | GSE245073 | GEO

Small molecule RIG-I agonist serves to adjuvant broad, multifaceted influenza virus vaccine immunity

Project description:Small molecule RIG-I agonist serves to adjuvant broad, multifaceted influenza virus vaccine immunity

| PRJNA848665 | ENA

Adjuvant Secretomes - Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures

Project description:Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures.

2016-03-14 | PXD003534 | Pride

Adjuvant Secretomes

Project description:Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures.

2016-07-20 | MSV000079960 | MassIVE

TLR7 variants in human lupus patients

Project description:While circumstantial evidence supports enhanced TLR7 signaling as a mechanism of human systemic autoimmune disease, we have lacked the proof afforded by lupus-causing TLR7 gene variants. Here we undertook a whole exome sequencing (WES) approach to identify novel TLR7 variants in human lupus patients. We establish the importance of TLR7 for human SLE pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

| EGAS00001005965 | EGA

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