Biology subjects

Tuju, J.

Publications and source records attributed to Tuju, J..

3 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↗

bioRxiv2018

Comprehensive profiling of antibodies against multiple infectious diseases in serum and the airway mucosa using synthetic peptide-based linear epitope microarrays

BackgroundDespite the considerable progress that has been achieved in the development of vaccines, infectious diseases continue to be the major cause of morbidity and mortality in developing countries. The first year of life remains the time of greatest risk with more than half of all deaths caused by infectious diseases in children under the age of five years occurring during this period. For most infections, antibodies are the strongest immune correlate of protective immunity and characterizing the breadth of the antibody repertoire against infectious diseases in early life is key to profiling individual disease risk.\n\nMethodsIn order to comprehensively profile the antibody repertoire against infectious diseases in early life, we developed a synthetic peptide-based microarray to simultaneously measure antibodies against forty one common infectious diseases. 82 empirically-validated linear B-cell epitopes were selected from the Immune Epitope Database (IEBD), expressed as synthetic peptides and printed onto microarray glass slides (microarray chip). The chip was used to simultaneously measure antigen-specific IgG and IgA in serum and mucosal samples from thirty eight infants and young children presenting to hospital with different illnesses. We also used the data from the microarray to estimate antibody decay kinetics for the five most frequently detected antigens during the first year of life.\n\nResultsA synthetic peptide microarray to measure antibodies against forty one infectious diseases was successfully developed. Although the combination of antigens that were recognized were different for each child, antigens derived from Epstein-Barr virus, poliovirus, Streptococcus pneumoniae, plasmodium falciparum and varicella zoster were recognized by most study participants. While the combination of antigens recognized in serum was generally similar as those recognized in mucosal samples, antibodies to antigens such as herpesvirus, rubella and echinococcus were more predominant in either serum or mucosal samples. With the exception of the pneumococcus, we observed a progressive decline in serum IgG specific to all the infections above in the first six months of life. Pneumococcal IgG in serum exhibited a continuous rise in the first six months of life.\n\nConclusionsWe successfully developed a synthetic peptide microarray and used it to profile the diversity of systemic and mucosal antibody against multiple infectious diseases in children. The data from the slide provide a snapshot overview of the breadth and kinetics of infectious disease antibodies early in life and opens the opportunity for conducting in-depth multi, multi-target serological studies of infectious diseases in future.

immunology↗