Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine

Zaman, Mehfuz; Skwarczynski, Mariusz; Malcolm, Jessica; Urbani, Carl N.; Jia, Zhongfan; Batzloff, Michael R.; Good, Michael F.; Monteiro, Michael J.; Tóth, István

doi:10.1016/j.nano.2010.10.002

Cited by 78 publications

(50 citation statements)

References 47 publications

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“…11,12,14 tert-Butyl acrylate polymer was chosen as a delivery platform for the vaccine because of its safety profile 15 and ability to serve as a self-adjuvanting moiety to induce both strong humoral and cellular immune responses. [16][17][18] In all of the previous challenge experiments, vaccine candidates were used to treat small tumors, as the vaccines were administered 3 days post tumor implantation. However, ideal therapeutic vaccines should also be able to eradicate large, well-established tumors.…”

Section: Introductionmentioning

confidence: 99%

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Hussein

Liu

Jia

et al. 2016

Bioorganic & Medicinal Chemistry

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Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8 + cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes.We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge.

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Section: Introductionmentioning

confidence: 99%

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Hussein

Liu

Jia

et al. 2016

Bioorganic & Medicinal Chemistry

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“…After co-evaporation with toluene (3 × 50 mL), the residue was dissolved in DCM (300 mL), washed with water (3 × 300 mL), ice-cold aqueous HCl-solution (5%), saturated NaHCO 3 -solution (3 × 100 mL), brine (3 × 100 mL), and dried (MgSO 4 ). The organic layer was concentrated and recrystallized from ethanol (6.3 g, 86% yield, C 15 system with a scattering angle of 173˚. DLS analyses were performed after ITC experiments and using the samples from microcalorimeter sample cell.…”

Section: Synthesis Of Peptides 2a-cmentioning

confidence: 99%

“…The tendency to form large aggregates can be explained by the relatively high hydrophobicity of synthesized amphiphiles [13,14]. To obtain more uniform particles, the nanoparticle might be selfassembled by dialysis of a solution of the lipopeptides in organic solvent against water [15,16].…”

Section: Introductionmentioning

confidence: 99%

Lipopeptides for the Fragment-Based Pharmaceutics Design

Ziora¹,

Wimmer²,

New³

et al. 2012

IJOC

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This paper describes the synthesis of peptide fragments for use in a new type of combinatorial discovery technology, in which the building blocks are brought together by non-covalent interactions, rather than direct chemical bonding. The building blocks of interest-in this case different amino acids-are converted to amphiphiles by attachment to lipid tails. The amphiphiles, when mixed together in aqueous phase, are designed so that they aggregate spontaneously to form micelles. The building blocks form the headgroups of each of the amphiphiles, and these headgroups cover the surface of the micelle in a dynamic close-packed fluid mosaic array. These building blocks come together so closely that twoor three-dimensional structures are created on the surface of the micelles, and these can be screened in biological assays to find out which combination of building blocks is able to elicit a biological response. Lipopeptides consisting of two residues of lipoamino acid and other amino acids moieties have been designed, synthesized, characterized and the ability of these constructs to form supra-molecular assemblies is demonstrated.

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“…Several approaches have been reported to overcome adjuvant-associated side effects [1,6]. We have extensively used exogenous lipids and polymers to form self-adjuvanting delivery systems that obviate the use of toxic adjuvants [8][9][10][11][12][13]. Recently, it has been reported that self-assembled peptides exclusively composed of endogenous amino acids were able to stimulate immune responses [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

Skwarczynski¹,

Kowapradit²,

Ziora³

et al. 2013

Bio Chem Comp

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Background: Peptide-based subunit vaccines require strong adjuvants (immunostimulant) for therapeutic potency. There is strong demand for the discovery of new safe adjuvants and vaccine delivery systems that can be produced in a highly controlled manner. The pH dependent self-assembly of isopeptide derivatives into fibrils has been reported. Appropriately designed fibrils may have adjuvanting potency. Methods: Isopeptides conjugated to B-cell peptide epitopes (antigens) were synthesized. Properties of the resultant conjugates and their ability to undergo O-N intramolecular acyl migration reaction were analysed by HPLC, circular dichroism, and transmission electron microscopy. Results: The conjugates were converted to "parent" peptides via the pH-triggered O-N acyl migration reaction. The parent peptides aggregated into fibrils. The differences in conjugates composition resulted in different fibril morphology. Aggregation of produced peptides induced desired secondary conformation of antigens (peptide epitopes). Conclusions:The isopeptide approach presented herein may serve as a new self-adjuvanting delivery system for peptide-based vaccines. Such vaccines could be stable when stored in a non-aggregative form, and then converted on demand to the active form in pH-controlled manner. The use of a vaccine that is solely composed of endogenous components may reduce vaccine-associated side effects.

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Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine

Cited by 78 publications

References 47 publications

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Lipopeptides for the Fragment-Based Pharmaceutics Design

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

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