A study of the alteration of B cell functionality associated with malaria and its impact on susceptibility to co-infections and vaccination

Exposure to malaria affects the frequency of B lymphocyte populations in peripheral blood, increasing atypical memory cells and decreasing cells similar to those in the splenic marginal zone. The function, mechanisms and consequences of these disturbances is unknown. Malaria is associated with a higher prevalence of certain bacterial and viral infections and with defective responses to vaccines. The hypothesis is that malaria alters the functionality of B lymphocytes and causes an ineffective immune response against infections and against vaccination. First, this project will describe the functional characteristics of B lymphocyte populations to identify mechanisms of immunomodulation by Plasmodium. Thisresearch project will characterize cell populations by flow cytometry, transcriptomics and in vitro culture and quantify antibodies and cytokine / chemokine production by Luminex. Second, the effect of malaria on immune cells of the spleen and its association with bacteremia will be investigated in autopsy samples of monkeys and humans, by means of immunofluorescence and functional assays. Third, it will investigate whether the expansion of B lymphocytes mediated by malaria affects the reactivation of the Epstein-Barr virus. Finally, the impact of B lymphocyte disturbances on the antigenic specificity and immunogenicity and efficacy of vaccines will be evaluated.

Basic Science
Immunology
Vaccines

Jan 2015 — Jun 2019

$177,320

Spain

Study of immune correlates of protection against malaria after vaccination with RTS,S/AS01E. A comprehensive immunological arm of a phase III double-blind, randomized, controlled multi-centre trial (MAL055-Immuno)