Enhancement of peptide immunogenicity by linear polymerization

Borrás‐Cuesta, Francisco; Fédon, Yann; Petit-Camurdan, Agnès

doi:10.1002/eji.1830180203

Cited by 68 publications

(45 citation statements)

References 16 publications

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“…Multimerization of peptides, such as that provided by dendrimeric constructs, has long been recognized as one of the most effective tools for enhancing peptide immunogenicity (11,54). In the present work, we report solid protection of pigs against FMDV challenge conferred by a dendrimeric peptide containing one B-and one T-cell immunodominant epitope.…”

Section: Discussionmentioning

confidence: 72%

Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Cubillos

Torre

Jakab

et al. 2008

J Virol

101

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The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptideimmunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

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Section: Discussionmentioning

confidence: 72%

Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Cubillos

Torre

Jakab

et al. 2008

J Virol

101

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“…It is worth mentioning that previous reports have described a proinflammatory role for THP. 44,45 These studies were based predominantly on in vitro or ex vivo data with highly aggregated, and potentially highly immunogenic, 46 urinary THP. 2 To this date, there is no evidence to suggest that interstitial THP exists in the same highly aggregated form.…”

Section: Discussionmentioning

confidence: 99%

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Micanovic¹,

Chitteti

Dagher³

et al. 2015

Journal of the American Society of Nephrology

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Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP 2/2 mice. Indeed, neutralization of IL-17 in THP 2/2 mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP 2/2 kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system.

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“…Our understanding of how T-cell help is provided to antibody producing B-cells has greatly benefited from immunization studies using peptide haptens linked to a peptide determinant sequence (TDJ2 recognized by T-cells (1)(2)(3)(4)(5)(6) as well as by immunization with mixtures of hapten and TD,, molecules injected in the same immunization site (7).…”

Section: Introductionmentioning

confidence: 99%

Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct

Lasarte

Sarobe

Gullón

et al. 1992

Cellular Immunology

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Peptide constructs were engineered by colinear synthesis of two short synthetic peptide determinants: a determinant recognized by T helper cells (TD,) and a determinant recognized by T cytotoxic cells (TD,). Three types of constructs were synthesized: TD,-TDr, , TD,-TD, , and TD,,-KK-TD,, where KK are two lysine residues. In vivo immunization with free construct induced cytolytic lymphocytes (CTL) only in the case of TD,-TD,,. However, immunization with spleen cells to which these constructs had been internalized by hypertonic shock, induced CTL activity in all three cases. No CTL could be induced after immunization with free TD, in either protocol. These results indicate that cell internalization of the construct might be essential for CTL induction, and also, that "help" from the TDr, seems to be required. o 1992 Academic PKSS, IX.

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Enhancement of peptide immunogenicity by linear polymerization

Cited by 68 publications

References 16 publications

Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct

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