Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes

Wu, Yaoying; Kelly, Sean H.; Sánchez-Pérez, Luis; Sampson, John H.; Collier, Joel H.

doi:10.1039/d0bm00521e

Cited by 38 publications

(38 citation statements)

References 65 publications

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“…However, the reduced immunogenicity of peptides has historically posed a challenge (57). Soluble peptides rarely elicit high-titer, long-lasting antibody responses without adjuvants, but biomaterials such as supramolecular nanofibers can be employed to produce long-lived, high-titer responses from these otherwise non-immunogenic peptides, in many cases without adjuvants (37,40,(58)(59)(60). These nanofiber materials have also been demonstrated to be stable, maintaining immunogenicity in vitro under prolonged conditions which otherwise cause loss of immunogenicity for complex folded proteins (61).…”

Section: Discussionmentioning

confidence: 99%

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

et al. 2020

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Current treatments for chronic immune-mediated diseases such as psoriasis, rheumatoid arthritis, or Crohn's disease commonly rely on cytokine neutralization using monoclonal antibodies; however, such approaches have drawbacks. Frequent repeated dosing can lead to the formation of anti-drug antibodies and patient compliance issues, and it is difficult to identify a single antibody that is broadly efficacious across diverse patient populations. As an alternative to monoclonal antibody therapy, anti-cytokine immunization is a potential means for long-term therapeutic control of chronic inflammatory diseases. Here we report a supramolecular peptide-based approach for raising antibodies against IL-17 and demonstrate its efficacy in a murine model of psoriasis. B-cell epitopes from IL-17 were co-assembled with the universal T-cell epitope PADRE using the Q11 self-assembling peptide nanofiber system. These materials, with or without adjuvants, raised antibody responses against IL-17. Exploiting the modularity of the system, multifactorial experimental designs were used to select formulations maximizing titer and avidity. In a mouse model of psoriasis induced by imiquimod, unadjuvanted nanofibers had therapeutic efficacy, which could be enhanced with alum adjuvant but reversed with CpG adjuvant. Measurements of antibody subclass induced by adjuvanted and unadjuvanted formulations revealed strong correlations between therapeutic efficacy and titers of IgG1 (improved efficacy) or IgG2b (worsened efficacy). These findings have important implications for the development of anti-cytokine active immunotherapies and suggest that immune phenotype is an important metric for eliciting therapeutic anti-cytokine antibody responses.

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Section: Discussionmentioning

confidence: 99%

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

et al. 2020

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“…[ 9,42 ] In a recent publication by Wu et al., Coil29 nanofibers were additionally shown to be minimally inflammatory as they triggered significantly lower levels of inflammatory cytokines and cell types compared to the traditional adjuvants Alum and SAS. [ 43 ]…”

Section: Methodsmentioning

confidence: 99%

Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8⁺ T‐Cell Responses

Fries¹,

Wu²,

Kelly³

et al. 2020

Advanced Materials

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to flow cytometry, cells were stained with DAPI to detect live and dead populations. Flow cytometry was preformed using a BD Canto FACS instrument and signals were compensated using single color controls. Counts of antigen specific T cells were taken by gating SIINFEKL specific T cells (CD4 − CD8 + B220 − F4/80 − Tetramer +) and multiplying the percentage of the total population by the total cell count after harvesting lymph nodes. here were performed under Duke University Institutional Animal Care and Use Committee protocol A264-18-11. Conflict of Interest J.H.C. and Y.W. are inventors on United States and PCT patent applications describing the Coil29 system.

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“…Insoluble aggregates based on amyloid fibril-forming peptides as the scaffolds for vaccines 50,53 are likely not efficiently transported to the lymph nodes and germinal centres 34,78 . An additional explanation for the efficiency of the β-annulus scaffolded vaccine may be a dynamic equilibrium between the oligomeric states of the assembly, which may facilitate the trafficking and presentation to B-lymphocytes.…”

Section: Immune Response Against the Scaffold In A Genetic Fusion Witmentioning

confidence: 99%

“…On the other hand fusion to peptide tags with high aggregation propensity has also been used for vaccines [49][50][51] . In this case the amyloid or helical assembly-promoting peptide tag induced formation of large fibers that were decorated with peptide epitopes [52][53][54] . For the induction of most efficient antibody response it is important that the antigens readily reach the lymph nodes where affinity maturation of the adaptive immune response takes place 35 .…”

Section: Introductionmentioning

confidence: 99%

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

Fink

Forstnerič

Hafner-Bratkovič

et al. 2020

Preprint

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Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and β-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue β-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

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Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes

Abstract: Coil29 nanofibers with integral T cell epitopes generated strong humoral responses and B cell memory by eliciting additional Tfh cells.

Cited by 38 publications

References 65 publications

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8⁺ T‐Cell Responses

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

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Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes

Abstract: Coil29 nanofibers with integral T cell epitopes generated strong humoral responses and B cell memory by eliciting additional Tfh cells.

Cited by 38 publications

References 65 publications

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8+ T‐Cell Responses

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

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Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8⁺ T‐Cell Responses