Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

Yang, Marie; Mine, Yoshinori

doi:10.1016/j.bbrc.2008.11.037

Cited by 45 publications

(37 citation statements)

References 29 publications

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“…1). OVA 323-339 (ISQAVHAAHAEINEAGR, hereafter referred to as OVA) is an H-2 b -restricted class II peptide containing multiple antigenic determinants, including known T and B cell epitopes (34). The self-assembling epitope peptide (O-Q11) was produced by solid phase synthesis and included a hydrophilic Ser-Gly-Ser-Gly spacer between the OVA and Q11 domains, with the OVA domain positioned at the N terminus (Fig.…”

Section: Resultsmentioning

confidence: 99%

A self-assembling peptide acting as an immune adjuvant

Rudra¹,

Tian

Jung³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

471

503

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The development of vaccines and other immunotherapies has been complicated by heterogeneous antigen display and the use of incompletely defined immune adjuvants with complex mechanisms of action. We have observed strong antibody responses in mice without the coadministration of any additional adjuvant by noncovalently assembling a Tand B cell epitope peptide into nanofibers using a short C-terminal peptide extension. Self-assembling peptides have been explored recently as scaffolds for tissue engineering and regenerative medicine, but our results indicate that these materials may also be useful as chemically defined adjuvants. In physiological conditions, these peptides self-assembled into long, unbranched fibrils that displayed the epitope on their surfaces. IgG1, IgG2a, and IgG3 were raised against epitope-bearing fibrils in levels similar to the epitope peptide delivered in complete Freund's adjuvant (CFA), and IgM production was even greater for the self-assembled epitope. This response was dependent on self-assembly, and the self-assembling sequence was not immunogenic by itself, even when delivered in CFA. Undetectable levels of interferon-gamma, IL-2, and IL-4 in cultures of peptide-challenged splenocytes from immunized mice suggested that the antibody responses did not involve significant T cell help.The development of vaccines and other immunotherapies has been challenged by imprecise antigen display and the use of heterogeneous immune adjuvants whose mechanisms of action are complex and incompletely understood. Synthetic peptides are useful as antigens because their precise chemical definition allows one to specify the exact epitopes against which an immune response is to be raised. However, peptides are poorly immunogenic by themselves and require coadministration with strong adjuvants. Although many adjuvants have been investigated for peptide immunotherapies to date, current strategies such as particulates (1, 2), oil emulsions (3), toll-like receptor (TLR) ligands (4), immunostimulating complexes (ISCOMs) (5), and other biologically sourced materials (6, 7) utilize chemically or structurally heterogeneous materials, making their characterization, mechanistic understanding, and regulatory approval challenging (1,8,9). This situation has motivated the pursuit of self-adjuvanting or adjuvant-free systems (10-12).A broad goal in the field of biomaterials is to produce synthetic scaffolds capable of presenting multiple cell-interactive components in spatially resolved networks (13,14). To accomplish this, supramolecular self-assembly is rapidly becoming a synthetic method of choice (15-17). One strategy that has received attention recently is based on fibrillized peptides, peptidomimetics, and peptide derivatives, which are being explored for a variety of biomedical and biotechnological applications, most notably as scaffolds for regenerative medicine (18,19) and defined matrices for cell culture (20,21). In these applications, selfassembled materials provide several advantages, including multifunctiona...

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Section: Resultsmentioning

confidence: 99%

A self-assembling peptide acting as an immune adjuvant

Rudra¹,

Tian

Jung³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

471

503

View full text Add to dashboard Cite

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“…A short assembly domain, called Q11 (acetyl-QQKFQFQFEQQ-amide), was used to form beta-sheet nanofibers in water and physiological buffers and preserve the molar ratio of the precursors in the assembled fibers. [15] We have previously synthesized peptide antigens such as OVA 323-339 (pOVA), which contains epitopes for both B cells and CD4+ T cells, [16] in tandem with Q11 (OVAQ11). When assembled into fibers and injected without additional adjuvants into mice, OVAQ11 activated antigen presenting cells in vivo and raised T-cell dependent antibody responses, [17, 18] yet it did not elicit the inflammation typically associated with conventional adjuvants.…”

Section: Introductionmentioning

confidence: 99%

Titrating T‐Cell Epitopes within Self‐Assembled Vaccines Optimizes CD4+ Helper T Cell and Antibody Outputs

Pompano

Chen

Verbus

et al. 2014

Adv Healthcare Materials

119

137

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Epitope content plays a critical role in determining T cell and antibody responses to vaccines, biomaterials, and protein therapeutics, but its effects are nonlinear and difficult to isolate. Here, molecular self-assembly was used to build a vaccine with precise control over epitope content, in order to finely tune the magnitude and phenotype of T helper and antibody responses. Self-adjuvanting peptide nanofibers were formed by co-assembling a high-affinity universal CD4+ T cell epitope (PADRE) and a B cell epitope from Staphylococcus aureus at specifiable concentrations. Increasing the PADRE concentration from μM to mM elicited bell-shaped dose-responses that were unique to different T cell populations. Notably, the epitope ratios that maximized T follicular helper and antibody responses differed by an order of magnitude from those that maximized Th1 or Th2 responses. Thus, modular materials assembly provides a means of controlling epitope content and efficiently skewing the adaptive immune response in the absence of exogenous adjuvant; this approach may contribute to the development of improved vaccines and immunotherapies.

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“…To design appropriate peptide IT vaccines, the immunogenic peptides that are able to stimulate a T-cell response and thus lead to immune regulation but yet are too short to be able to cross-link IgE on cell surfaces must first be defined. Works on defining these T-cell epitope peptide sequences for some food allergens, namely for peanut (Ara h 1 and Ara h 2) in humans and for egg (ovalbumin [OVA]) in mice, have now been reported [34][35][36][37]. In addition, there have been some reports of the use of peptide vaccines for peanut and egg in the murine model [38,39].…”

Section: Peptide Immunotherapymentioning

confidence: 98%

Vaccines and Immunomodulatory Therapies for Food Allergy

Lieberman

Nowak‐Węgrzyn

2011

Curr Allergy Asthma Rep

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The apparent increase in food allergy prevalence has led to a surge in the amount of clinical and basic science research dedicated to the field. At the current time, allergen avoidance remains the cornerstone of treatment; however, recent clinical trials investigating various forms of immunotherapy have opened doors to the possible future application of an active treatment strategy in everyday practice. In addition, improvements in molecular biology have allowed researchers to purify, clone, and modify allergens, thus laying the groundwork for research on vaccines using modified proteins of decreased allergenicity. Finally, various allergen-nonspecific immunomodulatory therapies are also being investigated as a means to alter the immune response to food allergens. With these emerging therapeutic strategies, it is hoped that practitioners will have options in caring for their food-allergic patients in the near future.

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Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

Cited by 45 publications

References 29 publications

A self-assembling peptide acting as an immune adjuvant

A self-assembling peptide acting as an immune adjuvant

Titrating T‐Cell Epitopes within Self‐Assembled Vaccines Optimizes CD4+ Helper T Cell and Antibody Outputs

Vaccines and Immunomodulatory Therapies for Food Allergy

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