ORCID Profile
0000-0002-5410-7562
Current Organisation
University of Oxford
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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: Springer Science and Business Media LLC
Date: 23-04-2013
DOI: 10.1038/SREP01706
Publisher: Springer Science and Business Media LLC
Date: 20-12-2011
DOI: 10.1038/NCOMMS1615
Publisher: Elsevier BV
Date: 12-2020
Publisher: The American Association of Immunologists
Date: 2014
Abstract: There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence of the following: 1) the ability to block the PfRH5–basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity 2) neutralizing mAbs bind spatially related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence 3) a brief exposure window of PfRH5 is likely to necessitate rapid binding of Ab to neutralize parasites and 4) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly neutralizing anti-malaria Abs and further encourage anti-PfRH5–based malaria prevention efforts.
Publisher: Oxford University Press (OUP)
Date: 21-10-2014
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Frontiers Media SA
Date: 04-06-2019
Publisher: American Society for Clinical Investigation
Date: 02-11-2017
Publisher: Elsevier BV
Date: 06-2019
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 21-05-2021
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Public Library of Science (PLoS)
Date: 08-11-2012
Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 25-10-2013
DOI: 10.1189/JLB.0513274
Abstract: New tools are required to expedite the development of an effective vaccine against the blood-stage infection with the human malaria parasite Plasmodium falciparum. This work describes the assessment of the ADRB assay in a mouse model, characterizing the functional interaction between antimalarial serum antibodies and FcRs upon neutrophils. We describe a reproducible, antigen-specific assay, dependent on functional FcR signaling, and show that ADRB activity is induced equally by IgG1 and IgG2a isotypes and is modulated by blocking FcR function. However, following immunization of mice with the blood-stage vaccine candidate antigen MSP142, no measurable ADRB activity was induced against PEMS and neither was vaccine efficacy modulated against Plasmodium yoelii blood-stage challenge in γ−/− mice compared with WT mice. In contrast, following a primary, nonlethal P. yoelii parasite challenge, serum from vaccinated mice and nonimmunized controls showed anti-PEMS ADRB activity. Upon secondary challenge, nonimmunized γ−/− mice showed a reduced ability to control blood-stage parasitemia compared with immunized γ−/− mice however, WT mice, depleted of their neutrophils, did not lose their ability to control infection. Thus, whereas neutrophil-induced ADRB against PEMS does not appear to play a role in protection against P. yoelii rodent malaria, induction of ADRB activity after challenge suggests that antigen targets of anti-PEMS ADRB activity remain to be established, as well as further supporting the observation that ADRB activity to P. falciparum arises following repeated natural exposure.
Publisher: Public Library of Science (PLoS)
Date: 18-06-2013
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3779160
Publisher: Frontiers Media SA
Date: 08-07-2015
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alexander Douglas.