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

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.