RATIONAL HIV VACCINE · Rational HIV vaccine design via mammalian cell display
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-08-01 → 2018-01-31
- Финансиране от ЕС
- 294 220 €
- Участници
- 1
- Схема
- MC-IOF
Линиите свързват координатора с партньорите.
Накратко на български
Дизайнът на антигени за ваксина срещу ХИВ търси начини да стимулира организма да произвежда антитела, които разпознават вируса. Това е важно, защото традиционните методи за ваксинация не успяват да се справят с устойчивостта на този патоген.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Rational HIV vaccine design via mammalian cell display
This project aims to investigate one of the greatest challenges in HIV vaccine research: how can broadly neutralizing antibodies be induced by vaccination in humans to target pathogens such as HIV that have been resistant to traditional vaccination approaches? AIM [i] Identification of HIV antigens that bind germ line and matured broadly neutralizing antibodies. This involved the generation of a panel of antigen variants and testing them for binding to neutralizing and germ line antibodies of this bnAb family and assessment of their ability to stimulate B cells expressing precursor antibodies. AIM [ii] Optimization of antigens to favour elicitation of broadly neutralizing antibodies. This required the generation of combinatorial antigen libraries for mammalian display and selection of antigens with higher affinity for germ line and mature bnAbs. This work used flow cytometry-based cell sorting and antigen mutagenesis protocols. AIM [iii] Using selected antigens to mature germ line antibodies to a broadly neutralizing phenotype. This aim involved extensive exploration of different cell sorting strategies and antibody mutagenesis methods. The optimized system was to use FACS to separate B cells that bound the antigen most tightly to enrich populations of cells with mutations that resulted in higher affinity. SIGNIFICANT RESULTS •Directed evolution of PGT121 germ line binding antigens via mammalian display which stimulate B cells encoding germ line antibodies[1,2]. •Generation of cell lines expressing bnAb heavy chain precursor and germ line antibodies via endogenous locus replacement system to enable in vitro. maturation[3,4]. •Development of methodology to translate in vitro affinity maturation into naïve human B cells. [1] Keystone HIV Vaccines meeting 2016: Steichen JM, McCoy LE, Kulp DW et al. [2] Steichen et al. Immunity, 2016. 45: p. 1–14. [3] Andrabi et al. Immunity. 2015 Nov 17;43(5):959-73. [4] Cell and Gene Therapy for HIV Cure 2016: Voss JE, Andrabi R, McCoy LE et al. FINAL GOAL: Validation of immune stimulation capacity of germline binding antigens to facilitate their development as immunogens. POTENTIAL IMPACT: In vitro maturation of HIV neutralizing antibodies, which will allow faster iteration of immunogen candidates and the development of potential prophylactics and therapeutics.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
This application proposes experiments to address one of the greatest challenges in HIV vaccine research: how can broadly neutralising antibodies be induced by vaccination in humans to target pathogens such as HIV, which are resistant to traditional vaccine approaches? The researcher and host labs will develop a mammalian display system using lentiviral vectors to express HIV proteins on the surface of mammalian cells and allow the in vitro evolution of different candidate vaccine immunogens in the outgoing host lab of Prof. Dennis Burton at The Scripps Research Institute. Optimisation of candidate vaccines will be achieved via random mutagenesis of the displayed immunogens followed by iterative rounds of selection for the ability to interact with novel highly potent broadly neutralizing HIV antibodies. The immunogens developed will initially be assessed for their ability to select for HIV neutralising antibodies in a novel in vitro antibody maturation system. The researcher will have access to first-rate career development advice from both hosts and via courses provided at both host institutes. The technical skills and translational skills acquired during the fellowship will be applied during the return phase in the HIV research lab of Prof. Deenan Pillay at University College London. The experimental skills acquired by the researcher will enrich the European research area during the return phase as they can be applied to other viral vaccine targets for which no effective vaccine is available e.g. influenza and hepatitis C. Thus the scientific advances made during this project have great potential significance for HIV vaccine research and the training received during the fellowship will place the researcher in an optimal position to start a research laboratory at a European Institution.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY COLLEGE LONDON · LondonКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз