Does disease tolerance delay the development of anti-parasite immunity in human malaria?

Anti-parasite immunity in human malaria develops slowly and is only ever partially efficacious. Meanwhile, immunity to severe malaria occurs early on in life and commonly only requires a few infections. This immunity is independent of anti-parasite immunity and thus can be defined as disease tolerance. Mechanisms of disease tolerance are still being elucidated. Previous human challenge work has demonstrated an explosive cytotoxic T cell response during the first malaria infection which is silenced in subsequent infections. This might impair T cell functions such as the CD4 T follicular helper (TFH) cells’ capacity to help germinal center (GC) B cells produce antibodies. Thus, the question is: does disease tolerance delay and/or diminish anti-parasite immunity? Matteo Putra will utilize samples from an upcoming controlled human malaria infection trial (BIO-004). He will examine changes in (1) TFH cells with mass cytometry and bone marrow organoids; (2) GC with B cell receptor repertoire sequencing to identify somatic hypermutation of GC B cells; and (3) antibodies with multiplex immunoassay, surface plasmon resonance, and growth inhibition and cytoadherence assays.

Vaccines (Immune Correlates)

Oct 2023 — Sep 2026

United Kingdom