Search bioRxiv⌕ Search

Biology subjects

Nyamako, L.

Publications and source records attributed to Nyamako, L..

2 recordsLinked to original sources
bioRxiv2022

Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge

Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication while the gold standard growth inhibition assay was not. The breadth of Fc-mediated effector function clearly discriminated grades of clinical immunity following challenge. These findings present a paradigm shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.

immunology↗
bioRxiv2022

High-throughput profiling of natural acquired humoral immune response to a large panel of known and novel full length ectodomain P. falciparum merozoite vaccine candidates under reduced malaria transmission.

Despite recent progress in the fight against malaria, it still remains a global health challenge necessitating development of intervention strategies. However, the search for malaria vaccine(s) has so far been very challenging. Multiple targets have been tested and so far only a few show promise with one having been endorsed by the WHO. In this study we explore the development of immunity in a low transmission setting, with very few documented re-infections, in order to understand the kinetics of the development and waning of immunity to current and novel blood-stage vaccine candidate antigens. To do this we performed a high-throughput measurement of natural acquired immunity against P. falciparum antigens utilizing a well-established micro-array platform based on the mammalian protein expression system. This large panel of known and novel recombinant full length ectodomain P. falciparum merozoite vaccine candidates were differently recognized by the immune system. Based on the overal spread of the data, some of these antigens induced the acquisition of high levels (1st tertile) of antibodies, among which included novel antigens such as PF3D7_1025300, PF3D7_1105800, PF3D7_1334400, PF3D7_0911300, PF3D7_1252300, PF3D7_1460600, PF3D7_1453100, PF3D7_0831400 and some induced low levels of antibodies (3rd tertile) while others induced moderate levels (4th tertile). In this longitudinal cohort with low level of malaria endemicity, acquisition of humoral immunity to these full length ectodomains P. falciparum antigens demonstrate different dynamics over-time, whereby it was either not acquired or if it was acquired it was either maintained or lost at different rates. These various identified novel antigens are potentially ideal candidates to be prioritized for further functional and or serological studies.

immunology↗