ORCID Profile
0000-0001-7133-5375
Current Organisations
University of Oxford
,
Pwani University College
,
Imperial College London
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Publisher: Springer Science and Business Media LLC
Date: 30-01-2019
Publisher: Springer Science and Business Media LLC
Date: 16-09-2015
DOI: 10.1038/SREP14081
Abstract: The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration and importantly assess reproducibility. Our standardized protocol involves testing each serum s le in singlicate with three independent neutrophil donors and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of s les from in iduals enrolled in immuno-epidemiological studies or clinical vaccine trials and requires only 6 μL of serum per s le. Using a cohort of 86 s les, we show that malaria-exposed in iduals induce higher ADRB activity than malaria-naïve in iduals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity and provides an important standardized cell-based assay in the field.
Publisher: American Society for Microbiology
Date: 05-2008
DOI: 10.1128/IAI.01585-07
Abstract: In iduals living in areas where malaria is endemic are repeatedly exposed to many different malaria parasite antigens. Studies on naturally acquired antibody-mediated immunity to clinical malaria have largely focused on the presence of responses to in idual antigens and their associations with decreased morbidity. We hypothesized that the breadth (number of important targets to which antibodies were made) and magnitude (antibody level measured in a random serum s le) of the antibody response were important predictors of protection from clinical malaria. We analyzed naturally acquired antibodies to five leading Plasmodium falciparum merozoite-stage vaccine candidate antigens, and schizont extract, in Kenyan children monitored for uncomplicated malaria for 6 months ( n = 119). Serum antibody levels to apical membrane antigen 1 (AMA1) and merozoite surface protein antigens (MSP-1 block 2, MSP-2, and MSP-3) were inversely related to the probability of developing malaria, but levels to MSP-1 19 and erythrocyte binding antigen (EBA-175) were not. The risk of malaria was also inversely associated with increasing breadth of antibody specificities, with none of the children who simultaneously had high antibody levels to five or more antigens experiencing a clinical episode (17/119 15% P = 0.0006). Particular combinations of antibodies (AMA1, MSP-2, and MSP-3) were more strongly predictive of protection than others. The results were validated in a larger, separate case-control study whose end point was malaria severe enough to warrant hospital admission ( n = 387). These findings suggest that under natural exposure, immunity to malaria may result from high titers antibodies to multiple antigenic targets and support the idea of testing combination blood-stage vaccines optimized to induce similar antibody profiles.
Publisher: Frontiers Media SA
Date: 11-12-2018
Publisher: Springer Science and Business Media LLC
Date: 07-2014
Publisher: Springer Science and Business Media LLC
Date: 20-12-2011
DOI: 10.1038/NCOMMS1615
Publisher: Public Library of Science (PLoS)
Date: 10-11-2011
Publisher: Springer Science and Business Media LLC
Date: 16-10-2014
Publisher: Elsevier BV
Date: 12-2008
Abstract: Effective immunity to malaria has been clearly demonstrated among in iduals naturally exposed to malaria, and can be induced by experimental infections in animals and humans. The large number of malaria antigens has presented a major challenge to identifying protective responses and their targets, and it is likely that robust immunity is mediated by responses to multiple antigens. These include merozoite surface antigens and invasion ligands, variant antigens on the surface of parasitized red blood cells, in addition to sporozoite and liver-stage antigens. Immunity seems to require humoral and cellular immune components, probably in co-operation, although the relative importance of each remains unclear. This review summarizes recent progress towards understanding the targets and mechanisms that are important for mediating immunity to malaria.
Publisher: Elsevier BV
Date: 03-2015
Publisher: F1000 Research Ltd
Date: 12-02-2019
DOI: 10.12688/GATESOPENRES.12897.1
Abstract: Measurement of malaria specific antibody responses represents a practical and informative method for malaria control programs to assess recent exposure to infection. Technical advances in recombinant antigen production, serological screening platforms, and analytical methods have enabled the identification of several target antigens for laboratory based and point-of-contact tests. Questions remain as to how these serological assays can best be integrated into malaria surveillance activities to inform programmatic decision-making. This report synthesizes discussions from a convening at Institut Pasteur in Paris in June 2017 aimed at defining practical and informative use cases for serology applications and highlights five programmatic uses for serological assays including: documenting the absence of transmission stratification of transmission measuring the effect of interventions informing a decentralized immediate response and testing and treating P. vivax hypnozoite carriers.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2022
DOI: 10.1038/S41467-021-27863-8
Abstract: Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in 65 adult travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a combination of five serological markers that detect exposure within the previous three months with % sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-in idual variation in response kinetics, and minimal persistence over time. Such serological exposure markers could be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.
Publisher: American Society for Clinical Investigation
Date: 02-11-2017
Publisher: Frontiers Media SA
Date: 13-10-2016
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-07-2014
DOI: 10.1126/SCITRANSLMED.3008705
Abstract: Uncharacterized proteins from the merozoite stage of Plasmodium falciparum provide new antigens for malaria blood-stage vaccine development.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-02-2023
DOI: 10.1126/SCITRANSLMED.ABN5993
Abstract: Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf _11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2015
Publisher: American Chemical Society (ACS)
Date: 11-03-2014
DOI: 10.1021/AC404188G
Abstract: Insecticide resistance is one of the most prevalent ex les of anthropogenic genetic change, yet our understanding of metabolic-based resistance remains limited by the analytical challenges associated with rapidly tracking the in vivo metabolites of insecticides at nonlethal doses. Here, using twin ion mass spectrometry analysis of the extracts of whole Drosophila larvae and excreta, we show that (i) eight metabolites of the neonicotinoid insecticide, imidacloprid, can be detected when formed by susceptible larval genotypes and (ii) the specific overtranscription of a single gene product, Cyp6g1, associated with the metabolic resistance to neonicotinoids, results in a significant increase in the formation of three imidacloprid metabolites that are formed in C-H bond activation reactions that is, Cyp6g1 is directly linked to the enhanced metabolism of imidacloprid in vivo. These results establish a rapid and sensitive method for dissecting the metabolic machinery of insects by directly linking single gene products to insecticide metabolism.
Publisher: Oxford University Press (OUP)
Date: 23-03-2018
Abstract: Human immunization with a polymorphic malaria vaccine candidate, MSP2, induced functional cross-reactive antibodies targeting conserved epitopes. This contrasts with naturally acquired antibodies, which target polymorphic epitopes, mediating immune escape. Findings reveal potential to overcome antigenic ersity for effective malaria vaccines.
Publisher: Cold Spring Harbor Laboratory
Date: 16-12-2020
DOI: 10.1101/2020.12.14.20242768
Abstract: Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could dramatically improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a novel combination of five serological markers (GAMA, MSP1, MSPDBL1 C- and N-terminal, and PfSEA1) that detect exposure within the previous 3-months with % sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-in idual variation in response kinetics, and minimal persistence over time. These serological exposure markers can be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1038/S41572-022-00399-X
Abstract: Asplenia (the congenital or acquired absence of the spleen) and hyposplenism (defective spleen function) are common causes of morbidity and mortality. The spleen is a secondary lymphoid organ that is responsible for the regulation of immune responses and blood filtration. Hence, asplenia or hyposplenism increases susceptibility to severe and invasive infections, especially those sustained by encapsulated bacteria (namely, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b). Asplenia is predominantly due to splenectomy for either traumatic events or oncohaematological conditions. Hyposplenism can be caused by several conditions, including haematological, infectious, autoimmune and gastrointestinal disorders. Anatomical disruption of the spleen and depletion of immune cells, especially IgM memory B cells, seem to be predominantly responsible for the clinical manifestations. Early recognition of hyposplenism and proper management of asplenia are warranted to prevent overwhelming post-splenectomy infections through vaccination and antibiotic prophylaxis. Although recommendations are available, the implementation of vaccination strategies, including more effective and immunogenic vaccines, is needed. Additionally, screening programmes for early detection of hyposplenism in high-risk patients and improvement of patient education are warranted.
Publisher: Oxford University Press (OUP)
Date: 02-08-2017
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Faith Hope Amongin Osier.