Active immunotherapy for C5a-mediated inflammation using adjuvant-free self-assembled peptide nanofibers

Hainline, Kelly M.; Haddad, Helena Freire; Gilpin, Anna; Curvino, Elizabeth J.; Varghese, Shyni; Collier, Joel H.

doi:10.1016/j.actbio.2024.02.042

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…Notably, the current therapeutic strategies are mostly focused on antibodies or small-molecule drugs targeting either C5a or its receptors. Nevertheless, repurposing small-molecule drugs as neutraligands of C5a, ,− repebodies, aptamers, antisense peptides, and self-assembled peptide nanofibers, including C5a-directed peptide vaccines, has also been hypothesized in the literature to possibly control the harmful signaling of excessive C5a in tissues. In this context, designer peptides composed of both coded and noncoded amino acids can be one of the alternative classes of therapeutic molecules targeting C5a that can bridge the gap between small molecules and biologics, especially when the FDA has approved more than 80 peptides and there are at least 170 peptides that are currently undergoing clinical evaluations for the treatment of various diseases .…”

Section: Introductionmentioning

confidence: 99%

Structure of Designer Antibody-like Peptides Binding to the Human C5a with Potential to Modulate the C5a Receptor Signaling

Ghosh,

Gupta,

Behera

et al. 2024

J. Med. Chem.

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C5a is an integral glycoprotein of the complement system that plays an important role in inflammation and immunity. The physiological concentration of C5a is observed to be elevated under various immunoinflammatory pathophysiological conditions in humans. The pathophysiology of C5a is linked to the “two-site” protein–protein interactions (PPIs) with two genomically related receptors, such as C5aR1 and C5aR2. Therefore, pharmacophores that can potentially block the PPIs between C5a–C5aR1 and C5a–C5aR2 have tremendous potential for development as future therapeutics. Notably, the FDA has already approved antibodies that target the precursors of C5a (Eculizumab, 148 kDa) and C5a (Vilobelimab, 149 kDa) for marketing as complement-targeted therapeutics. In this context, the current study reports the structural characterization of a pair of synthetic designer antibody-like peptides (DePA and DePA1; ≤3.8 kDa) that bind to hotspot regions on C5a and also demonstrates potential traits to neutralize the function of C5a under pathophysiological conditions.

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Section: Introductionmentioning

confidence: 99%

Structure of Designer Antibody-like Peptides Binding to the Human C5a with Potential to Modulate the C5a Receptor Signaling

Ghosh,

Gupta,

Behera

et al. 2024

J. Med. Chem.

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Multi‐Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation

Freire Haddad,

Roe,

Xie Fu

et al. 2024

Adv Healthcare Materials

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The anaphylatoxins C3a and C5a are products of the complement cascade that play important and interrelated roles in health and disease. Both are potential targets for anti‐inflammatory active immunotherapies in which a patient's own immune system is stimulated to produce therapeutic immune responses against problematic self‐molecules. However, the complex and time‐dependent interrelations between the two molecules make dual targeting challenging. To investigate a dual‐target active immunotherapy against C3a and C5a and to systematically study the effect of varied degrees of responses against both targets, the study employed self‐assembled peptide immunogens capable of displaying a broad range of epitope compositions and Design‐of‐Experiments (DoE) approaches. Peptide nanofibers contained B‐cell epitopes of C3a and C5a in defined quantities, and intranasal immunization raised systemic and mucosal immunity against each target. In a lipopolysaccharide‐induced model of sepsis, increasing anti‐C5a responses are protective, whereas increasing anti‐C3a responses are detrimental, and survival rates are negatively correlated with anti‐C3a/anti‐C5a IgG titer ratio. This work highlights the interplay between the two molecules by making use of a modular, defined, and easily adjusted biomaterial‐based active immunotherapy platform.

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Nanoparticles in Subunit Vaccines: Immunological Foundations, Categories, and Applications

Liang,

Yao,

Liu

et al. 2024

Small

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Subunit vaccines, significant in next‐generation vaccine development, offer precise targeting of immune responses by focusing on specific antigens. However, this precision often comes at the cost of eliciting strong and durable immunity, posing a great challenge to vaccine design. To address this limitation, recent advancements in nanoparticles (NPs) are utilized to enhance antigen delivery efficiency and boost vaccine efficacy. This review examines how the physicochemical properties of NPs influence various stages of the immune response during vaccine delivery and analyzes how different NP types contribute to immune activation and enhance vaccine performance. It then explores the unique characteristics and immune activation mechanisms of these NPs, along with their recent advancements, and highlights their application in subunit vaccines targeting infectious diseases and cancer. Finally, it discusses the challenges in NP‐based vaccine development and proposes future directions for innovation in this promising field.

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Active immunotherapy for C5a-mediated inflammation using adjuvant-free self-assembled peptide nanofibers

Cited by 4 publications

References 42 publications

Structure of Designer Antibody-like Peptides Binding to the Human C5a with Potential to Modulate the C5a Receptor Signaling

Structure of Designer Antibody-like Peptides Binding to the Human C5a with Potential to Modulate the C5a Receptor Signaling

Multi‐Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation

Nanoparticles in Subunit Vaccines: Immunological Foundations, Categories, and Applications

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