Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens

Reddy, Sreenivasulu B.; Anders, Robin F.; Cross, Nadia; Müeller, Ivo; Senn, Nicolas; Stanisic, Danielle I.; Siba, Peter; Wahlgren, Mats; Kironde, Fred; Beeson, James G.; Persson, Kristina

doi:10.1186/s12866-015-0461-1

Cited by 14 publications

(11 citation statements)

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“…While antibody avidity is theoretically important in the function of an antibody response [ 45 ], there are few available empiric data to support the relationship between avidity and immunity in malaria. Reddy et al found that individuals with higher antibody avidity to P. falciparum antigens were less likely to experience malaria during follow-up [ 21 , 46 ]. In an RTS,S malaria vaccine trial, investigators did not find an association between antibody avidity to circumsporozoite protein and protection after the last dose of vaccination among children, but they did show that the change in avidity between second and third vaccination was associated with a 54% reduced risk of acquiring malaria [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda

Ssewanyana

Arinaitwe

Nankabirwa

et al. 2017

Malar J

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BackgroundPeople living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection.MethodsCross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA.ResultsWithin a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1.ConclusionAvidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as well as their clinical consequences will require additional investigation, ideally utilizing longitudinal data and investigation of a broader array of responses.

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Section: Discussionmentioning

confidence: 99%

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda

Ssewanyana

Arinaitwe

Nankabirwa

et al. 2017

Malar J

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“…In addition, the results highlighted that the sensors at 1 nM are more sensitive to an antibody binder with a KD £ 1 nM ( Figure S4B, C). Importantly, this threshold is equivalent to the median affinity reported for polyclonal antibody repertoires (Poulsen et al, 2007;Reddy et al, 2015).…”

Section: Engineering Split Luminescent Biosensors (Spluc) For Sars-comentioning

confidence: 87%

Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection

Elledge

Zhou

Byrnes

et al. 2020

Preprint

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Current serology tests for SARS-CoV-2 antibodies mainly take the form of enzyme-linked immunosorbent assays or lateral flow assays, with the former being laborious and the latter being expensive and often lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost solution-based assay to detect antibodies in serum, plasma, whole blood, and saliva, using rationally designed split luciferase antibody biosensors (spLUC). This new assay, which generates quantitative results in as short as 5 minutes, substantially reduces the complexity and improves the scalability of COVID-19 antibody tests for point-of-care and broad population testing.

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“…Even though the first malaria vaccine, GSK′s Plasmodium falciparum circumsporozoite protein (CSP)-based Mosquirix (RTS,S), (Wilby et al, 2012 ) is expected to enter the market within the next 6–12 months, there is still an urgent demand for a malaria vaccine that reliably delivers long lasting protection against infection, clinical manifestation and transmission of the disease. RTS′S (Chattopadhyay et al, 2003 ; Richards et al, 2013 ; Penny et al, 2015 ; Reddy et al, 2015 ; RTS,S Clinical Trials Partnership, 2015 ) presents pre-erythrocytic stage epitopes and targets the parasite in an early phase of its life cycle within the human host. However, Mosquirix does not induce complete protection, and efficacy decreases rapidly over the first 24 months after immunization (RTS,S Clinical Trials Partnership et al, 2012 ; Moorthy et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…Many epidemiological studies involving donors from malaria endemic areas associate protective immunity with antibody responses against various, predominantly merozoite antigens (Osier et al, 2008 ) including Pf MSP1, Pf AMA1, Pf MSP4, Pf MSP8, Pf EBA175, and Pf RIPR. Many of these proteins elicit in vitro parasite growth-inhibitory antibody responses after animal immunization experiments (Sim et al, 2001 ; Stowers et al, 2002 ; Moss et al, 2012 ), but despite substantial efforts (Richards et al, 2013 ; Penny et al, 2015 ; Reddy et al, 2015 ; RTS,S Clinical Trials Partnership, 2015 ) the roles of these proteins in protective immunity remains poorly understood, making it difficult to select rational targets for the design of an ultimate malaria vaccine candidate.…”

Section: Introductionmentioning

confidence: 99%

Application of a Scalable Plant Transient Gene Expression Platform for Malaria Vaccine Development

et al. 2015

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Despite decades of intensive research efforts there is currently no vaccine that provides sustained sterile immunity against malaria. In this context, a large number of targets from the different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates. None of these candidates has fulfilled expectations, and as long as we lack a single target that induces strain-transcending protective immune responses, combining key antigens from different life cycle stages seems to be the most promising route toward the development of efficacious malaria vaccines. After the identification of potential targets using approaches such as omics-based technology and reverse immunology, the rapid expression, purification, and characterization of these proteins, as well as the generation and analysis of fusion constructs combining different promising antigens or antigen domains before committing to expensive and time consuming clinical development, represents one of the bottlenecks in the vaccine development pipeline. The production of recombinant proteins by transient gene expression in plants is a robust and versatile alternative to cell-based microbial and eukaryotic production platforms. The transfection of plant tissues and/or whole plants using Agrobacterium tumefaciens offers a low technical entry barrier, low costs, and a high degree of flexibility embedded within a rapid and scalable workflow. Recombinant proteins can easily be targeted to different subcellular compartments according to their physicochemical requirements, including post-translational modifications, to ensure optimal yields of high quality product, and to support simple and economical downstream processing. Here, we demonstrate the use of a plant transient expression platform based on transfection with A. tumefaciens as essential component of a malaria vaccine development workflow involving screens for expression, solubility, and stability using fluorescent fusion proteins. Our results have been implemented for the evidence-based iterative design and expression of vaccine candidates combining suitable P. falciparum antigen domains. The antigens were also produced, purified, and characterized in further studies by taking advantage of the scalability of this platform.

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Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens

Cited by 14 publications

References 68 publications

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda

Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection

Application of a Scalable Plant Transient Gene Expression Platform for Malaria Vaccine Development

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