Unravelling the heterogoneity and function of monocytes in vaccination and immunity to malaria (VaMonos)

Malaria remains one of the major public health concerns worldwide. An effective vaccine against malaria is a global health priority to advance toward the elimination goals of this infectious disease. WHO recently recommended the RTS,S/AS01E malaria vaccine for African children for areas with high and medium malaria transmission. However, RTS,S has a moderate efficacy that needs to be improved. Understanding its mode of action and why a high proportion of vaccinated children are not protected will guide rational development of second-generation better vaccines. Whereas antibodies induced by RTS,S are associated with protection, the exact effector mechanisms have not been well defined.

Additionally, there is high heterogeneity in the antibody levels induced by the vaccine in African children and the factors and mechanisms associated with this heterogeneity are uncertain. There are also are vaccinated children who despite high antibody titers are not protected. Monocytes are crucial innate cells for early vaccine responses through inflammatory responses, antigen-presenting functions and interactions with T cells that shape the subsequent acquired response to the vaccine. This cell type is also important for antibody effector functions via binding to Fc receptors (FcR) through mechanisms such as antibodydependent phagocytosis. Therefore, particular monocyte subsets may impact vaccine outcomes.

The project will use cryopreserved peripheral blood mononuclear cells and data collected in (i) an immunological study ancillary to the RTS,S pediatric phase 3 trial, before and after vaccination, and (ii) in a trial performed in malaria-naïve adults to optimize the dose and route of sporozoites injections in controlled human malaria infection studies. For sample selection, it will be used exhaustive antibody and clinical data already gathered in the RTS,S immunology study to define high and low vaccine responders, protected and protected children and malaria-exposed and unexposed individuals. It will be performed in-depth immune phenotyping of monocytes through spectral flow cytometry and single-cell RNA-Seq and subsequently in vitro assays to assess the function of the identified monocyte subsets.

Project Details

Basic Science
Vaccines (Immune Correlates)

Sep 2023 — Aug 2026

$349,385

Spain