Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach

Fox, Christopher B.; Orr, Mark T.; Hoeven, Neal Van; Parker, Sarah C.; Mikasa, Traci J.T.; Phan, Tony; Beebe, Elyse A.; Nana, Ghislain Ismael; Joshi, Sharvari W; Tomai, Mark A.; Elvecrog, James; Fouts, Timothy; Reed, Steven G.

doi:10.1016/j.jconrel.2016.11.011

Cited by 56 publications

(60 citation statements)

References 25 publications

(38 reference statements)

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“…The strong adjuvanticity of 3M‐052 exhibited in our study was also observed in other reports in which 3M‐052 was formulated into vaccines using lipid‐based or combined lipid‐Alhydrogel® delivery platforms. Fox et al reported that a liposome‐Alhydrogel® formulation with 3M‐052 enhanced the antigen‐specific IgG1 and IgG2c titers and frequency of T H 1 cytokine‐producing CD4 + memory cells of a tuberculosis vaccine in mice.…”

Section: Discussionsupporting

confidence: 88%

“…To address this limitation, the lipophilic derivative 3M‐052 was developed as a next‐generation TLR7/8 agonist that is retained at the injection site longer . Because of the lipophilic nature of 3M‐052, liposomes or other lipid‐based delivery vehicles have been used for subcutaneous, intramuscular, or intratumoral injections of 3M‐052 …”

Section: Introductionmentioning

confidence: 99%

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3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

et al. 2017

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It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (T 1) immune response. In this study, we investigated the adjuvanticity of the Toll-like receptor (TLR) 7/8 agonist 3M-052 in combination with the Leishmania donovani 36-kDa nucleoside hydrolase recombinant protein antigen (NH36). NH36 and 3M-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). The loading efficiency for NH36 was 83% and for 3M-052 was above 95%. In vitro stimulation of bone marrow-derived dendritic cells, measured by IL-12 secretion, demonstrated that 3M-052 (free or MP-formulated) had a concentration-dependent immunostimulatory effect with an optimum concentration of 2 µg/mL. In immunogenicity studies in BALB/c mice, MP-formulated NH36 and 3M-052 elicited the highest serum titers of T 1-associated IgG2a and IgG2b antibodies and the highest frequency of IFNγ-producing splenocytes. No dose dependency was observed among MP/NH36/3M-052 groups over a dose range of 4-60 µg 3M-052 per injection. The ability of MP-formulated NH36 and 3M-052 to elicit a T 1-biased immune response indicates the potential for PLGA MP-formulated 3M-052 to be used as an adjuvant for leishmaniasis vaccines. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1587-1594, 2018.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

et al. 2017

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“…S2B). Accumulating evidence suggests that tissue retention is an indispensable characteristic for TLR7 agonist function as a vaccine adjuvant [25,26]. To test the activity of T7-EA in vivo, we injected 35 nmol T7-EA, T7, R848 or normal saline in the gastrocnemius muscles [intramuscular (i.m.)]…”

Section: T7-ea Is a Tlr7-selective Agonist That Induces Local Cytokinmentioning

confidence: 99%

A novel TLR7 agonist as adjuvant to stimulate high quality HBsAg-specific immune responses in an HBV mouse model

Tang

Zhu

et al. 2020

J Transl Med

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Background: The global burden of hepatitis B virus (HBV) infection in terms of morbidity and mortality is immense. Novel treatments that can induce a protective immune response are urgently needed to effectively control the HBV epidemic and eventually eradicate chronic HBV infection. Methods:We designed and evaluated an HBV therapeutic vaccine consisting of a novel Toll-like receptor 7 (TLR7) agonist T7-EA, an Alum adjuvant and a recombinant HBsAg protein. We used RNA-seq, ELISA and hTLR7/8 reporting assays to characterize T7-EA in vitro and real-time PCR to evaluate the tissue-retention characteristics in vivo. To evaluate the adjuvant potential, we administrated T7-EA intraperitoneally in a formulation with an Alum adjuvant and HBsAg in normal and HBV mice, then, we evaluated the HBsAg-specific immune responses by ELISA and Elispot assays.Results: T7-EA acted as an hTLR7-specific agonist and induced a similar gene expression pattern as an unmodified TLR7 ligand when Raw 264.7 cells were exposed to T7-EA; however, T7-EA was more potent than the unmodified TLR7 ligand. In vivo studies showed that T7-EA had tissue-retaining activity with stimulating local cytokine and chemokine expression for up to 7 days. T7-EA could induce Th1-type immune responses, as evidenced by an increased HBsAgspecific IgG2a titer and a T-cell response in normal mice compared to mice received traditional Alum-adjuvant HBV vaccine. Importantly, T7-EA could break immune tolerance and induce persistent HBsAg-specific antibody and T-cell responses in an HBV mouse model. Conclusions:T7-EA might be a candidate adjuvant in a prophylactic and therapeutic HBV vaccine.

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“…The number of immunostimulatory agonists targeting PRR in recombinant antigenic peptide vaccines is increasing [59]. Anti-tuberculosis vaccines have used a diverse array of molecular adjuvants directed against multiple Toll-like receptors (TLR) and have elicited a surprisingly diverse set of responses [59–66].…”

Section: Adjuvantsmentioning

confidence: 99%

“…Anti-tuberculosis vaccines have used a diverse array of molecular adjuvants directed against multiple Toll-like receptors (TLR) and have elicited a surprisingly diverse set of responses [59–66]. Comparative analysis between novel adjuvants and BCG suggests that stimulation of antigen presenting cells via a single PRR may in some cases be sufficient to induce activated T cells [21].…”

Section: Adjuvantsmentioning

confidence: 99%

Tuberculosis vaccines — perspectives from the NIH/NIAID Mycobacteria vaccine testing program

Izzo

2017

Current Opinion in Immunology

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The development of novel vaccine candidates against infections with Mycobacterium tuberculosis has highlighted our limited understanding of immune mechanisms required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but new studies are required to identify other mechanisms that may be necessary. Novel vaccines formulations that invoke effector cells such as innate lymphoid cells may provide an environment that promote effector mechanisms including T cell and B cell mediated immunity. Identifying pathways associated with killing this highly successful infectious agent has become critical to achieving the goal of reducing the global tuberculosis burden.

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Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach

Cited by 56 publications

References 25 publications

3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

A novel TLR7 agonist as adjuvant to stimulate high quality HBsAg-specific immune responses in an HBV mouse model

Tuberculosis vaccines — perspectives from the NIH/NIAID Mycobacteria vaccine testing program

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