Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Skwarczynski, Mariusz; Zhao, Guangzu; Boer, Jennifer C.; Ozberk, Victoria; Azuar, Armira; Cruz, Jazmina L. Gonzalez; Giddam, Ashwini Kumar; Khalil, Zeinab; Pandey, Manisha; Shibu, Mohini A.; Hussein, Waleed M.; Nevagi, Reshma J.; Batzloff, Michael R.; Wells, James W.; Capon, Robert J.; Plebanski, Magdalena; Good, Michael F.; Tóth, István

doi:10.1126/sciadv.aax2285

Cited by 89 publications

(84 citation statements)

References 41 publications

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“…Peptide-based self-assembled nanostructures are one of the major class among the emerging subunit vaccines in recent years and have been shown as capable to elicit long-lasting antibody titer, [40,41] induce CD8 + T cell responses, [42,43] enhance the antitumor immune response, [44,45] provide protection against bacterial or viral infections. [43,46,47] Interestingly, a biotin-SA interaction based, pathogen-specific, self-assembled subunit vaccine system has been generated and pre-clinically tested in less than 120 days, [48] and is currently being used as a differentiated, rapid approach to finding a COVID-19 vaccine. Thus, in newly emerging pandemic, for rapid production of an effective vaccine, subunit vaccines and peptide-based self-assembled vaccine systems are promising candidates.…”

Section: Resultsmentioning

confidence: 99%

Biotin Functionalized Self‐Assembled Peptide Nanofiber as an Adjuvant for Immunomodulatory Response

Demircan

Tohumeken

Gündüz

et al. 2020

Biotechnology Journal

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Biotinylated peptide amphiphile (Biotin-PA) nanofibers, are designed as a noncovalent binding location for antigens, which are adjuvants to enhance, accelerate, and prolong the immune response triggered by antigens. Presenting antigens on synthetic Biotin-PA nanofibers generated a higher immune response than the free antigens delivered with a cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) (TLR9 agonist) adjuvant. Antigen attached Biotin-PA nanofibers trigger splenocytes to produce high levels of cytokines (IFN-, IL-12, TNF-, and IL-6) and to exhibit a superior cross-presentation of the antigen. Both Biotin-PA nanofibers and CpG ODN induce a Th-1-biased IgG subclass response; however, delivering the antigen with Biotin-PA nanofibers induce significantly greater production of total IgG and subclasses of IgG compared to delivering the antigen with CpG ODN. Contrary to CpG ODN, Biotin-PA nanofibers also enhance antigen-specific splenocyte proliferation and increase the proportion of the antigen-specific CD8(+) T cells. Given their biodegradability and biocompatibility, Biotin-PA nanofibers have a significant potential in immunoengineering applications as a biomaterial for the delivery of a diverse set of antigens derived from intracellular pathogens, emerging viral diseases such as COVID-19, or cancer cells to induce humoral and cellular immune responses against the antigens.

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Section: Resultsmentioning

confidence: 99%

Biotin Functionalized Self‐Assembled Peptide Nanofiber as an Adjuvant for Immunomodulatory Response

Demircan

Tohumeken

Gündüz

et al. 2020

Biotechnology Journal

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“…Polyleucine (L15), when conjugated to B-cell epitope, self-assembled into nanoparticles. These particles induced the production of high antibody titers and protected model animals against GAS [ 306 ] and hookworm [ 307 ] infections. Polyglutamic and aspartic acids (E10 and D10) formed self-adjuvanting polyelectrolyte-based complexes when mixed with peptide antigen and trimethyl chitosan (TMC), while a simple mixture of antigen with TMC did not induce strong immune responses [ 308 , 309 , 310 ].…”

Section: Peptide-based Therapiesmentioning

confidence: 99%

A Global Review on Short Peptides: Frontiers and Perspectives

et al. 2021

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Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

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“…as required by changing the type and number of incorporated HAAs. While we recently demonstrated that the pHAA system can self-assemble into chain-like nanoparticle aggregates and serve as an injectable vaccine against GAS, 23 the ability of such a system to deliver antigens orally has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Development of natural and unnatural amino acid delivery systems against hookworm infection

Bartlett

Skwarczyński

Xin

et al. 2020

PRNANO

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Peptide-based vaccines consist of short antigen fragments derived from a specific pathogen. Alone, these peptide fragments are poorly or non-immunogenic; however, when incorporated into a proper delivery system, they can trigger strong immune responses. To eliminate the need for toxic and often ineffective oral adjuvants, we designed single molecule-based self-adjuvating vaccines against hookworms using natural and unnatural hydrophobic amino acids. Two vaccine conjugates were synthesized, consisting of B-cell epitope p3, derived from the hookworm Na-APR-1 protein; universal T-helper peptide P25; and either double copies of unnatural lipoamino acid (2-amino-D,L-eicosanoic acid), or ten copies of the natural amino acid leucine. After challenge with the model hookworm, Nippostrongylus brasiliensis, mice orally immunized with the conjugates, but without adjuvant, generated antibody responses against the hookworm epitope, resulting in significantly reduced worm and egg burdens compared to control mice. We have demonstrated that vaccine nanoparticles composed exclusively of natural amino acids can be effective even when administered orally.

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Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Cited by 89 publications

References 41 publications

Biotin Functionalized Self‐Assembled Peptide Nanofiber as an Adjuvant for Immunomodulatory Response

Biotin Functionalized Self‐Assembled Peptide Nanofiber as an Adjuvant for Immunomodulatory Response

A Global Review on Short Peptides: Frontiers and Perspectives

Development of natural and unnatural amino acid delivery systems against hookworm infection

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