Self‐Assembled Peptide Amphiphile Micelles Containing a Cytotoxic T‐Cell Epitope Promote a Protective Immune Response In Vivo

Black, Matthew; Trent, Amanda; Kostenko, Yulia; Lee, Joseph Saeyong; Olive, Colleen; Tirrell, Matthew

doi:10.1002/adma.201200209

Cited by 222 publications

(204 citation statements)

References 46 publications

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“…Also, since the micelle delivery device is comprised of the peptide itself, it is more than 80% peptide vaccine by weight which is considerably higher than the ∼25% maximum peptide loading possible with other nanoparticle delivery devices (47). Previous research has shown peptide amphiphile micelles presenting a cytotoxic T cell epitope act as selfadjuvants that induce a strong immune response (33), so the same platform technology was tested for its ability to facilitate an antibody-mediated response.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptor 2 (TLR-2) stimulation activity was characterized similarly to a previously established technique (33). Human embryonic kidney cells (HEK-293) transfected to express the TLR-2 receptor on their surface which when stimulated causes a luciferase reporter gene to fluoresce were generously provided as a gift by Professor Greg Barton.…”

Section: Toll-like Receptor 2 Stimulationmentioning

confidence: 99%

“…The micelles were then allowed to equilibrate overnight. J8-diC 16 micelles were characterized by previously defined methodologies (33,35,36) including critical micelle concentration (CMC) analysis, transmission electron microscopy (TEM), and circular dichroism (CD). CMC was measured by fluorescent sequestration where varying concentrations of J8-diC 16 were exposed to 1 mM 1,6-diphenyl-1,3,5-hexatriene (DPH) which greatly increases in fluorescence intensity when trapped within the micelle core.…”

Section: Micelle Formation and Characterizationmentioning

confidence: 99%

“…Also, peptide amphiphile micelles are comprised of a high concentration of peptide (30), inhibit peptide degradation (31), and can greatly increase peptide intracellular delivery (32). Recent research by the Tirrell Group has shown that peptide amphiphile micelles that display a tumor-specific cytotoxic T cell epitope can function as a self-adjuvanting vaccine delivery system capable of inducing a tumor-suppressing immune response when given prophylactically (33). In this report, the potential for peptide amphiphile micelles to act as a self-adjuvanting platform for the delivery of a GAS peptide vaccine was investigated.…”

Section: Introductionmentioning

confidence: 99%

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Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

Trent

Ulery

Black

et al. 2014

AAPS J

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Abstract. Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC 16 ) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC 16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC 16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC 16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam 3 Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

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Section: Discussionmentioning

confidence: 99%

Section: Toll-like Receptor 2 Stimulationmentioning

confidence: 99%

Section: Micelle Formation and Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

Trent

Ulery

Black

et al. 2014

AAPS J

Self Cite

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“…[1][2][3][4][5] Moreover, aggregates obtained from self-assembling peptides have been proposed as vaccines. [6][7][8] Peptides containing the minimal amino acid sequences necessary to stimulate an adaptive immune response are weak immunogens and require either strong adjuvants or their organization into nanometer-sized micelles to be effective for the development of the immune response. 9 While the use of adjuvants limits the clinical application of immunogenic peptides (because of their high intrinsic toxicity), the assembling of peptide amphiphiles (PAs) in micelles boosts peptide-specific immune responses without causing any undesirable side effects.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment

Accardo¹,

Vitiello²,

Tesauro³

et al. 2014

IJN

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The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB 409–505 and gD 301–309 , selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 ⋅ 10 −7 mol ⋅ Kg −1 ; hydrodynamic radii (R H ) between 50–80 nm, and a zeta potential (ζ) around − 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 μM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.

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