A combined carrier-adjuvant system of peptide nanofibers and toll-like receptor agonists potentiates robust CD8+ T cell responses

Abstract

Improving CD8+ T cell responses activated by subunit vaccination is crucial for improving vaccine efficacy and safety. Here we report a carrier-adjuvant system composed of self-assembling peptide nanofibers presenting an immunodominant antigen from herpes simplex virus (HSV) and toll-like receptor (TLR) agonists that induces robust effector and memory CD8+ T cell responses in mice. The effector function of vaccine-induced CD8+ T cells was influenced by the type of TLR agonist. The use of CpG (TLR9 agonist) resulted in significantly greater specific in vivo cytotoxicity and trended towards more cells producing both IFN-γ and TNF-α compared to gardiquimod (TLR7 agonist). Prime-boost immunization with peptide nanofibers combined with either adjuvant resulted in development of HSV-specific CD8+ memory T cells further demonstrating the capability of the carrier-adjuvant system to induce strong HSV-specific CD8+ T cell responses. Inclusion of peptide epitope-nanofibers in protein-based subunit vaccines should increase the functional spectrum of the vaccine-elicited immune response and protection.

Multivalent display of chemical signals on self‐assembled peptide scaffolds

“…In a study done by Rudra et al, [61] a modified cocaine hapten was covalently attached to (FKFE) and memory CD8+ T cell responses in mice. [64] Additionally, Mycobacterium tuberculosis specific CD8+ T cell epitopes (IMYNYPAM and QQWNFAGI) have been displayed on (FKFE) 2 . [66] Intranasal immuni-…”

Biomaterials for vaccine-based cancer immunotherapy

“…Recent advancements in molecular adjuvants, including TLR agonists, have accelerated the development of cancer vaccines, as traditional adjuvants ( e.g. alum and Freund’s adjuvant) fail to induce potent CTL and Th1 immune responses[26, 242–244]. One of the most important discoveries from the last decade is that the co-delivery of antigen and molecular adjuvants encapsulated within a biomaterial carrier tends to induce stronger immune responses than the delivery of soluble antigens and adjuvants in the absence of a carrier[245].…”

Influences of Nanocarrier Morphology on Therapeutic Immunomodulation

“…In contrast, nano-spheres and cubes were retained in the lysosome and induced secretion of high levels of pro-inflammatory cytokines, TNF-α, IL-6, IL-12 and GM-CSF, that induced even greater antibody responses (Figure 3). Rudra et al has sought to elucidate the specific mechanism through which peptide nanofibers exhibit future science group www.futuremedicine.com this immuostimulatory effect on APCs, dendritic cells and macrophages [57,58]. They conclude that autophagy plays a central role in the adjuvant mechanism of these supramolecular structures and highlight that future studies should focus on how adjusting physicochemical properties of the fibers (size, shape, stability) will alter their adjuvant properties.…”

“…The authors postulated that the nanofiber-based formulations outperformed the alum-based control due to their ability to more effectively control the release of antigen. Furthermore, the formulation incorporating positively charged nanofibers elicited a long-lasting antibody Filamentous Peptides CD8 T cell stimulation without adjuvant [71] Filamentous gel Peptides T cell response, tumor growth [52] Filamentous gel Peptides CD8 T cell activation, proliferation [54] Filamentous gel PGA-chitosan Antigen specific cross-presentation, titers, adjuvanticity [72] Filamentous gel, spherical PEG-PPS Morphology transition, release [73] Filamentous scaffold Peptides CD8 T cell, memory, effector response [57] Filamentous, flat pSarc-LLAIB IgM production, growth inhibition, ligand density [46] Filamentous, flat, spherical Silver Uptake; mast cell degranulation [43] Filamentous, spherical PEG-PEE; PEG-PCL Uptake, circulation [32] Filamentous, spherical PEG-PPS Biodistribution; lymph nodes, spleen [45] Flat MoS2 Payload uptake, stimulation [61] Flat Graphene oxide Antigen display, uptake, endosomal escape [67] Raspberry, gibbous, spherical Polypyrrole Targeting, MRI visualization [50] Rod Silica Biodistribution, excretion [34] Rod, cubic, spherical Gold Uptake, antibody production, adjuvanticity [56] Rod, spherical Silica Renal excretion [36] Rod, spherical PAA, PVP, PEI Uptake, antibody titers [41] Rod response that failed to decline even after 28 weeks. This enhanced potency occurred due to an increase in antigen uptake by dendritic cells, which the authors attributed to the effect of the positive surface charge of the D-peptide nanofibers.…”