HEИндивидуална стипендия2023–2025

Bmem-Malaria · Identifying cellular and molecular features of protective anti-malaria B cell response

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-09-01 → 2025-08-31
Финансиране от ЕС: 187 624 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Имунният отговор на B-клетките към различни видове паразити се анализира чрез проби от клинични изпитвания върху хора. Това помага за разбирането на защитните механизми на организма, което е важно за разработването на по-ефективни ваксини срещу малария.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Identifying cellular and molecular features of protective anti-malaria B cell response

Malaria is one of the major infectious diseases that causes high disease burden worldwide. According to World malaria Report 2024, 263 million cases and 597,000 deaths are related to malaria in 2023. Most of the disease incidences are observed in low- and middle-income countries (LMICs) in sub-Saharan Africa, South America and Southeast Asia. Importantly, the deaths related to malaria disease are observed mainly in children. In the last two decades, two malaria vaccines have been approved by WHO and implemented in several countries in Africa. Even with low protective efficacy, the vaccines is making major differences in the vaccinees. Howeve, the disease is not eradicated and vaccine-induced protective efficacy wanes, highlighting the need to develop highly efficacious malaria vaccines. In this project, I proposed to perform an in-depth immunological analysis of B cell response to malaria, making use of the unique clinical trial samples from controlled human malaria infection studies. To that end, I characterized cellular and humoral immunity against two distinct genetically attenuated parasite exposures in malaria-naive individuals. This thorough analysis revealed a broad convergence between the two arms of adaptive immunity to the parasites. Furthermore, this study also uncovered malaria antigens targeted by the antibody response, that are unique to late- but not early-liver stage arresting parasites. Additionally, from the samples, I isolated B cells and characterized the evolution of their response over repeated parasite exposure. Collectively, this work advanced our understanding on different components of adaptive immunity that contribute to protection against malaria and thereby help develop efficacious vaccines.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Malaria is one of the leading life-threatening diseases with a reported 627,000 deaths and 241 million infections in 2020, mostly in low-income countries. Despite the advances gained by control measures, malaria incidence by Plasmodium falciparum (Pf) has plateaued in the last decade. Intervention through vaccines and antibody therapy shows promising results, yet long-lasting protective immunity remains unattainable. Anti-malaria memory B cells comprise transcriptionally distinct sub-populations, but their contribution to protective immunity is unclear. Here, I plan to combine state-of-the-art strategies to identify the cellular and molecular features of protective immunity offered by B cells and encoded antibodies, respectively. To that end, I will use the unique samples from controlled human malaria infection trials to isolate memory B cells reactive to Pf antigens, obtain transcriptome and immunoglobulin (Ig) gene sequences at the single cell level and measure antibody inhibitory properties at the monoclonal level. Transcripts signifying resting, activated or exhausted phenotype will allow memory B cell clustering, whereas Ig gene features will help define clonal expansion and selection strength of antibodies. By cloning and testing antibodies in specialized in vitro and in vivo assays, I aim to discover potent inhibitory antibodies targeting different parasite developmental stages. I will reveal the protective antibody molecular properties defined by Ig gene features, affinity, and epitope specificity. By single-cell level integration of transcriptome and antibody functionality for the first time, this project will not only deliver potent parasite inhibitory antibodies of therapeutic potential but also lay a clear blueprint for attaining protective immunity through future vaccine designs. This fellowship will support me in acquiring interdisciplinary expertise and advancing my career as a leading scientist in B cell immunology and malaria vaccinology.

Оригинален текст от CORDIS (на английски).

Участници

ACADEMISCH ZIEKENHUIS LEIDEN · LeidenКоординаторНидерландия