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Construction of recombinant mimotopes for induction of neutralizing antibodies against HIV-1 gp120 glycoprotein using high-affinity binders approach

Public support

  • Provider

    Ministry of Health

  • Programme

    Programme to support medical applied research in 2015 to 2022

  • Call for proposals

    Zdravotnický AV 1 (SMZ0201501)

  • Main participants

    Univerzita Palackého v Olomouci / Lékařská fakulta

  • Contest type

    VS - Public tender

  • Contract ID

    15-32198A

Alternative language

  • Project name in Czech

    Příprava rekombinantních mimotopů indukujících neutralizační protilátky proti HIV-1 gp120 glykoproteinu pomocí technologie vysokoafinitních ligandů

  • Annotation in Czech

    Vývoj vakcíny proti HIV-1 infekci je brzděn enormní variabilitou obalového glykoproteinu (Env), cíle neutralizačních protilátek. Identifikace sady monoklonálních protilátek neutralizujících široké spektrum variant HIV-1 (bn-mAb), reagujících s Env glykany, jako součástí jejich epitopu, nabízí novou cestu vývoje vakcíny. Jelikož kompozitní epitopy obsahující glykany jsou méně efektivní imunogeny než proteinové epitopy navrhujeme vyvinout sadu peptidů napodobujících epitopy rozlišované výše popsanými bn-mAb pomocí metody vysoce afinitních ligandů (binderů) vyvinutých spolunavrhovatelem projektu. Bindery budou selektovány na základě jejich specifické vazby na jednotlivé bn-mAb, budou fúzovány s albuminem a kotvami a ve formě proteoliposomů nebo DNA vakcín užity k imunizaci experimentálních zvířat. Poté bude charakterizována specificita, afinita a neutralizační aktivita sérových protilátek. Přístup skýtá možnost identifikovat kandidátní antigen pro vakcínu proti HIV-1 a představuje platformu pro vývoj vakcín napodobujících glykanové epitopy navozujících dobrou imunologickou paměť.

Scientific branches

  • R&D category

    AP - Applied research

  • CEP classification - main branch

    EC - Immunology

  • CEP - secondary branch

    EI - Biotechnology and bionics

  • CEP - another secondary branch

  • OECD FORD - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

    20801 - Environmental biotechnology<br>20802 - Bioremediation, diagnostic biotechnologies (DNA chips and biosensing devices) in environmental management<br>20803 - Environmental biotechnology related ethics<br>20901 - Industrial biotechnology<br>20902 - Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation<br>20903 - Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials<br>30102 - Immunology<br>30401 - Health-related biotechnology<br>30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)<br>30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])<br>30404 - Biomaterials (as related to medical implants, devices, sensors)<br>30405 - Medical biotechnology related ethics<br>40401 - Agricultural biotechnology and food biotechnology<br>40402 - GM technology (crops and livestock), livestock cloning, marker assisted selection, diagnostics (DNA chips and biosensing devices for the early/accurate detection of diseases) biomass feedstock production technologies, biopharming<br>40403 - Agricultural biotechnology related ethics

Completed project evaluation

  • Provider evaluation

    V - Vynikající výsledky projektu (s mezinárodním významem atd.)

  • Project results evaluation

    The main aim of the project has set several successive goals that eventually cluster together and lead to the development of a vaccine against HIV1. Modern methods of reverse vaccination were used is the project, the selection of immunogenic antigens was performed by the method of molecular fingerprinting of neutralizing antibodies that proved to be successful. Selected high affinity antigens then formed the basis for a vaccine that was successfully tested in an animal models. In a view of a potential adaptation of the vaccine to human practice, the possible sublingual application on the mouse model was also tested during the project. Tested vaccines resulted in the generation of neutralizing antibodies against HIV1. Therefore, the project fulfilled its goals, the results of successive steps were summarized in 4 high impact publications, the key fifth publication is in the review process. Overall, the project fulfilled the task with excellent results, laying the foundation for further

Solution timeline

  • Realization period - beginning

    May 1, 2015

  • Realization period - end

    Dec 31, 2018

  • Project status

    U - Finished project

  • Latest support payment

    Jun 28, 2018

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP19-MZ0-NV-U/02:1

  • Data delivery date

    Sep 16, 2019

Finance

  • Total approved costs

    6,200 thou. CZK

  • Public financial support

    6,200 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK