Convergent peptide libraries, or mixotopes, to elicit or to identify specific immune responses

Gras‐Masse, Hélène; Georges, Bertrand; Estaquier, Jérǒme; Tranchand-Bunel, D.; Tartar, André; Druilhe, Pierre; Auriault, C.

doi:10.1016/s0952-7915(99)80038-7

Cited by 6 publications

(7 citation statements)

References 41 publications

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“…Attempts have also been made to redirect the immune response to conserved neutralization epitopes by deleting some or most of the variable loops from Env, but the results were not satisfactory [192,193]. Other approaches to overcome the problem of extensive antigenic variability include using as immunogen either artificial consensus sequences based on the most common amino acid in each position in an alignment [194,195], or alternatively combinatorial convergent peptide libraries consisting of thousands of V3 peptides known as mixotopes that are recognized as a single entity by immune receptors [196]. Other strategies to deal with the existence of many antigenic variants by means of polyvalent vaccine cocktails have also been proposed [197].…”

Section: One Of the Many Hurdles To Be Overcome By An Hiv-1 Vaccine Imentioning

confidence: 99%

Requirements for empirical immunogenicity trials, rather than structure-based design, for developing an effective HIV vaccine

Regenmortel

2011

Arch Virol

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The claim that it is possible to rationally design a structure-based HIV-1 vaccine is based on misconceptions regarding the nature of protein epitopes and of immunological specificity. Attempts to use reverse vaccinology to generate an HIV-1 vaccine on the basis of the structure of viral epitopes bound to monoclonal neutralizing antibodies have failed so far because it was not possible to extrapolate from an observed antigenic structure to the immunogenic structure required in a vaccine. Vaccine immunogenicity depends on numerous extrinsic factors such as the host immunoglobulin gene repertoire, the presence of various cellular and regulatory mechanisms in the immunized host and the process of antibody affinity maturation. All these factors played a role in the appearance of the neutralizing antibody used to select the epitope to be investigated as potential vaccine immunogen, but they cannot be expected to be present in identical form in the host to be vaccinated. It is possible to rationally design and optimize an epitope to fit one particular antibody molecule or to improve the paratope binding efficacy of a monoclonal antibody intended for passive immunotherapy. What is not possible is to rationally design an HIV-1 vaccine immunogen that will elicit a protective polyclonal antibody response of predetermined efficacy. An effective vaccine immunogen can only be discovered by investigating experimentally the immunogenicity of a candidate molecule and demonstrating its ability to induce a protective immune response. It cannot be discovered by determining which epitopes of an engineered antigen molecule are recognized by a neutralizing monoclonal antibody. This means that empirical immunogenicity trials rather than structural analyses of antigens offer the best hope of discovering an HIV-1 vaccine.

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Section: One Of the Many Hurdles To Be Overcome By An Hiv-1 Vaccine Imentioning

confidence: 99%

Requirements for empirical immunogenicity trials, rather than structure-based design, for developing an effective HIV vaccine

Regenmortel

2011

Arch Virol

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“…Therefore, fuzzy logic, as a problem-solving control system, has been widely used for the control of complex industrial systems, such as elevators or trains, as well as for household and entertainment electronics and other expert systems. Though vagueness and continuity is a ubiquitous feature of biomedical sciences, fuzzy logic was only recently implemented in the immunology field [13], and importantly it has already begun to be employed for exploring the mechanisms of antigen recognition of both T-cell receptors (TCRs) and antibodies [14,15].…”

Section: Definition Of Fuzzy Logicmentioning

confidence: 99%

“…Accordingly, each T-or B-cell clone is capable of recognizing and responding to distinct antigenic epitopes, and no receptor of each T-or B-cell clones can bind to two structurally distinct epitopes. However, recent immunological progress has revealed that antigenic recognition is rather vague and T cells and antibodies can recognize a given self or nonself antigen to a certain degree [14,15]. Structural studies revealed that there is no clear-cut minimum difference in binding affinity or atomic positions at the antigen±antibody interface, which can serve as an absolute criterion for deciding whether two epitopes are the same or not [14,15].…”

Section: Fuzzy Antigenic Recognition and Maintenance Of Naive T Cellsmentioning

confidence: 99%

“…However, recent immunological progress has revealed that antigenic recognition is rather vague and T cells and antibodies can recognize a given self or nonself antigen to a certain degree [14,15]. Structural studies revealed that there is no clear-cut minimum difference in binding affinity or atomic positions at the antigen±antibody interface, which can serve as an absolute criterion for deciding whether two epitopes are the same or not [14,15]. The binding sites of antibodies that characterize immunological specificity consist of a number of epitopes [14,15].…”

Section: Fuzzy Antigenic Recognition and Maintenance Of Naive T Cellsmentioning

confidence: 99%

“…Structural studies revealed that there is no clear-cut minimum difference in binding affinity or atomic positions at the antigen±antibody interface, which can serve as an absolute criterion for deciding whether two epitopes are the same or not [14,15]. The binding sites of antibodies that characterize immunological specificity consist of a number of epitopes [14,15]. Evidently, when random peptide libraries were employed to identify antigenic determinants recognized by a monoclonal antibody, mimic peptides have been frequently found with high affinities for antibodies yet lacking sequence similarity to the original antigenic protein [15].…”

Section: Fuzzy Antigenic Recognition and Maintenance Of Naive T Cellsmentioning

confidence: 99%

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Beyond Self and Nonself: Fuzzy Recognition of the Immune System

Leng

Bentwich

2002

Scand J Immunol

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Leng Q, Bentwich Z. Beyond Self and Nonself: Fuzzy Recognition of the Immune System. Scand J Immunol 2002;56:224±232 Self±nonself discrimination of the immune system is a widely accepted principle of immunology; however, abundant existing and physiologic functions of harmless autoimmunity as well as degeneracy of antigen recognition expose the over-simplification of the two-valued doctrine. Here, based on infinite-value fuzzy logic, we propose that the immune repertoire, as a consequence of central tolerance, is able to recognize both self and nonself antigens to a certain degree, compensating for the inadequacy of the two-valued self±nonself doctrine. Subthreshold recognition of self antigens is necessary for the generation of regulatory T cells, survival of both naive and memory T cells and other physiologic functions. The kind and magnitude of the immune response depend on the affinity between the antigen (self and foreign) and the T-cell receptor, and microenvironmental and cellular threshold. The outcome of self±nonself discrimination is influenced fundamentally by central tolerance and further dynamic regulation of threshold molecules both in time and space. Understanding the fuzzy feature of the immune system may shed light on mechanisms of autoimmune diseases, cancers and other chronic diseases, and lead to the design of novel vaccines or immunotherapies.

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Requirements for Empirical Immunogenicity Trials, Rather than Structure-Based Design, for Developing an Effective HIV Vaccine

Regenmortel¹

2019

HIV/AIDS: Immunochemistry, Reductionism and Vaccine Design

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Convergent peptide libraries, or mixotopes, to elicit or to identify specific immune responses

Cited by 6 publications

References 41 publications

Requirements for empirical immunogenicity trials, rather than structure-based design, for developing an effective HIV vaccine

Requirements for empirical immunogenicity trials, rather than structure-based design, for developing an effective HIV vaccine

Beyond Self and Nonself: Fuzzy Recognition of the Immune System

Requirements for Empirical Immunogenicity Trials, Rather than Structure-Based Design, for Developing an Effective HIV Vaccine

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