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HEIndividual fellowship2023–2025

IDSpnBmem · Characterization of protective anti-pneumococcal B cell immunity after immunization.

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-04-01 → 2025-03-31
EU contribution
€203,464
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

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Results in brief

Characterization of protective anti-pneumococcal B cell immunity after immunization.

Pneumonia is the leading infectious cause of death in children worldwide, accounting for nearly a million infant deaths yearly. Likewise, community-acquired pneumonia is a leading cause of severe illness and death among the elderly, with Streptococcus pneumoniae (pneumococcus) being the principal etiologic bacterial agent. Pneumococcal infections in both children and adults are preventable by vaccination; however current vaccines do not offer the level of protection needed due to multiple limitations and insight on protective cellular immunity is currently incomplete. Memory B cells (Bmem) are central in immunization, as re-exposure to antigens leads to rapid generation of high-affinity antibody responses. The magnitude of Bmem after vaccination is associated with long-lasting humoral immunity and increased booster response. Studies with the experimental human pneumococcal carriage (EHPC) model, in which healthy adult volunteers are intranasally inoculated with S. pneumoniae, show that naturally-acquired serotype-specific IgG+ Bmem correlate with protection in healthy UK adults. However, whether specific subsets vaccine-induced B cells responses are associated to protection remains unknown. Therefore, characterization of the cellular responses to pneumococcal immunization by integrating multiple analytical approaches may provide critical insight into protective immunity. The objectives of IDSpnBmem were to phenotypically characterize pneumococcal antigen-specific B cells and elucidate understanding of protective immunity via linking phenotypic and transcriptomic characterization with functionality of the humoral response. This was performed using two methods (spectral flow cytometry and 10X single-cell sequencing) from participant of different age groups (children, adults and elderly) exposed to various immunization methods (polysaccharide conjugate vaccination, polysaccharide non-conjugate vaccination, natural exposure and experimental human challenge) and compare across antigen specificities.

Data: CORDIS, © European Union

Project objective

Pneumococcal pneumonia is one of the leading causes of death in children and the elderly worldwide. Pneumococcal vaccines have significantly reduced global incidence of pneumococcal disease, however, current vaccines show varying efficacy among covered serotypes, leading to insufficient level of protection for complete herd immunity. Memory B cells (Bmem) are responsible for high-affinity and long-lasting humeral immunity, and serotype-specific Bmem are associated with increased protection against pneumococcal colonization. Despite their critical role, to date, information on immunization-elicited cellular responses is limited. Here, I propose to characterize pneumococcal serotype-specific B cells for 25 cellular markers, transcriptome and BCR sequence, and link this phenotypic profile with functionality by analyzing recombinantly expressed antibodies. These analysis will involve the integration of 33-colour spectral flow cytometry, 10X next generation RNA and BCR sequencing, B cell cloning, generation of recombinant monoclonal antibodies and functional analysis by antibody avidity and opsonophagocytic capacity. Via computational science, using a data-driven and high-dimensional approach, I aim to identify the phenotypes of protective serotype-specific B cell immunity by analyzing individuals of different ages (children and adults), geographic location (Malawi and Europe) and immunization route (vaccination and colonization). This information will shed light on cellular differences of non-efficient vaccine responses, and may aid in development of improved vaccines. Additionally, the proposed activities and training by experts will be critical for my career development to become an independent researcher in the field of clinical immunology and vaccinology.

Original text from CORDIS.

Participants

  • ACADEMISCH ZIEKENHUIS LEIDEN · LeidenCoordinatorNetherlands

Links

Data: CORDIS, © European Union