Confronting the degeneracy of convergent combinatorial immunogens, or ‘mixotopes’, with the specificity of recognition of the target sequences

Gras‐Masse, Hélène; Boutillon, Christophe; Diesis, Eric; Deprez, Benoı̂t; Tartar, André

doi:10.1016/s0264-410x(97)00079-0

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…Retroinverso peptide analogues, with modifications in the amide bond, are more resistant to protease degradation [241], and have been used to enhance the immunogenicity of FMDV antigenic peptide vaccines, with promising results in mice and guinea-pigs [34]. The use of mixtures of peptides covering different antigenic variants, termed mixotopes [108], may decrease the chances of selection of escape mutants. New immunodominant T cell epitopes in FMDV structural and non-structural proteins [31,240] could be included in the design of peptide vaccines in an attempt to overcome the restriction introduced by the MHC polymorphism in their recognition by T cells.…”

Section: Peptide Vaccinesmentioning

confidence: 99%

Foot-and-mouth disease virus: a long known virus, but a current threat

et al. 2001

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-Foot-and-mouth disease virus (FMDV) was the first animal virus identified. Since then, FMDV has become a model system in animal virology and a considerable amount of information on its structure, biology and vaccinology has been obtained. However, the disease that this virus produces (FMD) still constitutes one of the main animal health concerns. In this review, we have attempted to summarise the state of the knowledge in different basic and applied areas of FMDV research, with emphasis on those aspects relevant to the control of the disease. FMDV / structure / immunity / vaccine / variability / diagnosisRésumé -Le virus de la fièvre aphteuse : un virus connu de longue date, qui demeure une menace. Le virus de la fièvre aphteuse a été le premier virus animal identifié. Depuis lors, il est devenu un système modèle en virologie animale, et une quantité importante d'informations sur sa structure, sa biologie et sa vaccinologie a été obtenue. Cependant la maladie provoquée par ce virus constitue encore une inquiétude majeure en santé animale. Dans cette revue, nous avons tenté de résumer l'état des connaissances dans différents domaines de recherche, à la fois fondamentaux et appliqués, sur le virus de la fièvre aphteuse, en mettant l'accent sur les aspects relatifs au contrôle de la maladie. virus de la fièvre aphteuse / immunité / vaccin / variabilité / diagnostic

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Section: Peptide Vaccinesmentioning

confidence: 99%

Foot-and-mouth disease virus: a long known virus, but a current threat

et al. 2001

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“…The elicited antibody population was able to distinguish minor sequential changes in the different antigens. The level of degeneracy of the mixotopes that were still able to stimulate specific immune responses was such (1,s 109 combinatorial sequences) that only synergistic, collective recognition of a continuum of multiple components could explain our observations (4)(5)(6). A limited number of short sequences that shared some homology with distantly related peptides (such as ELI in this V3 model) were present in the mixture, but did not induce detectable non-specific antibody responses.…”

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confidence: 77%

Detection of human antibodies using “convergent” combinatorial peptide libraries or “mixotopes” designed from a nonvariable antigen: Application to the EBV viral capsid antigen p18

Tranchand-Bunel

Auriault

Diesis

et al. 1998

The Journal of Peptide Research

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We have previously described the use of synthetic combinatorial “convergent” libraries, or “mixotopes” as immunogens or as antigens to represent naturally hypervariable sequences. The success of this approach suggests that such a mixture of closely related peptides could, at least in part, conveniently represent a nonvariable epitope during its multiple interactions with an antibody population. To address this possibility, we have designed from a non‐variable immunodominant peptide of the EBV‐viral capsid antigen of 18 kD (VCAp18) a series of three mixotopes containing from 65,000 to 16 million combinatorial sequences. The reactivity of VCAp18 and its three derived mixotopes was examined in ELISA towards a collection of 74 human sera from documented EBV‐negative or EBV‐positive donors, and analyzed in terms of sensitivity and specificity. Following the observation that the two least degenerated mixotopes could improve the sensitivity of detection of some sera of low reactivity for VCAp18, we decided to combine each mixotope with the VCAp18 peptide. In the case of the least degenerated mixotope in combination with VCAp18, sensitivity and specificity for immunoenzymatic EBV‐serodiagnosis, were enhanced to 100%. Our results suggest that synthetic “convergent” combinatorial peptide libraries or “mixotopes,” designed from nonvariable antigens, could be useful adjuncts to an antigenic single‐sequence peptide in immunoenzymatic serodiagnosis.

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“…An alternative approach aimed to cover the identification of a wide spectrum of V3 epitopic sequences is the generation of combinatorial peptide libraries, called mixotopes [43,44]. Mixotopes comprise several peptides that represent variable positions of the V3 loop, and act as model antigens for recognition of the immune system.…”

Section: Direct Antigen Vaccination Using a Series Of Presentation Stmentioning

confidence: 99%

Enhancing Immunogenicity and Cross-Reactivity of HIV-1 Antigens by In Vivo Targeting to Dendritic Cells

et al. 2012

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Current retroviral treatments have reduced AIDS to a chronic disease for most patients. However, given drug-related side effects, the emergence of drug-resistant strains and the persistence of viral replication, the development of alternative treatments is a pressing need. This review focuses on recent developments in HIV immunotherapy treatments, with particular emphasis on current vaccination strategies for optimizing the induction of an effective immune response by the recruitment of dendritic cells. In addition to cell-based therapies, targeted strategies aiming to deliver synthetic HIV peptides to dendritic cell-specific receptors in vivo will be discussed.

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Confronting the degeneracy of convergent combinatorial immunogens, or ‘mixotopes’, with the specificity of recognition of the target sequences

Cited by 9 publications

References 15 publications

Foot-and-mouth disease virus: a long known virus, but a current threat

Foot-and-mouth disease virus: a long known virus, but a current threat

Detection of human antibodies using “convergent” combinatorial peptide libraries or “mixotopes” designed from a nonvariable antigen: Application to the EBV viral capsid antigen p18

Enhancing Immunogenicity and Cross-Reactivity of HIV-1 Antigens by In Vivo Targeting to Dendritic Cells

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