Evaluation of Pregnancy Malaria Vaccine Candidates: The Binding Inhibition Assay

Saveria, Tracy; Duffy, Patrick E.; Fried, Michal

doi:10.1007/978-1-4939-2815-6_19

Cited by 8 publications

(4 citation statements)

References 8 publications

(8 reference statements)

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“…The UCPH and Inserm teams routinely perform the well-established Petri dish BIA method [ 29 ] as well as a high throughput technique based on the use of 96-well microtitre plates [ 30 ]. In both approaches, CSA is coated on a plastic substrate as a platform for binding of infected erythrocytes, and BIA with sera or other inhibitors are performed under static conditions (Fig.…”

Section: Immunoassaysmentioning

confidence: 99%

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

Chêne

Houard

Nielsen

et al. 2016

Malar J

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Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines.

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Section: Immunoassaysmentioning

confidence: 99%

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

Chêne

Houard

Nielsen

et al. 2016

Malar J

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“…The parasite suspension was preincubated with plasma diluted 1:5 for 30 min at room temperature, then allowed to bind to the immobilized receptor for 30 min at room temperature. Plates were washed with PBS to remove unbound cells, fixed, stained, and quantified as previously described ( 15 ). Level of inhibition was defined based on the level of IE binding in the presence of a pool of plasma samples collected from malaria-naïve adults in the USA, using the formula [100-((Ntest/Ncontrol) x 100)].…”

Section: Methodsmentioning

confidence: 99%

Acquisition of antibodies that block Plasmodium falciparum adhesion to placental receptor chondroitin sulfate A with increasing gravidity in Malian women

Mahamar,

Traore,

Swihart

et al. 2024

Front. Immunol.

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In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.

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“…The CSA binding inhibition assay was evaluated in a static binding inhibition assay using immobilized CSA as previously described [75]. In brief, CSA (Sigma) at 10 μg/ml in PBS was coated as 15 μl spots on a 100 x 15 mm Petri dish (Falcon 351029) by overnight incubation at 4˚C.…”

Section: Binding Inhibition Assay (Bia)mentioning

confidence: 99%

Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for a placental malaria vaccine

Ma,

Salinas,

Orr-Gonzalez

et al. 2024

PLoS Pathog

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Placental accumulation of Plasmodium falciparum infected erythrocytes results in maternal anemia, low birth weight, and pregnancy loss. The parasite protein VAR2CSA facilitates the accumulation of infected erythrocytes in the placenta through interaction with the host receptor chondroitin sulfate A (CSA). Antibodies that prevent the VAR2CSA-CSA interaction correlate with protection from placental malaria, and VAR2CSA is a high-priority placental malaria vaccine antigen. Here, structure-guided design leveraging the full-length structures of VAR2CSA produced a stable immunogen that retains the critical conserved functional elements of VAR2CSA. The design expressed with a six-fold greater yield than the full-length protein and elicited antibodies that prevent adhesion of infected erythrocytes to CSA. The reduced size and adaptability of the designed immunogen enable efficient production of multiple variants of VAR2CSA for use in a cocktail vaccination strategy to increase the breadth of protection. These designs form strong foundations for the development of potent broadly protective placental malaria vaccines.

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Evaluation of Pregnancy Malaria Vaccine Candidates: The Binding Inhibition Assay

Cited by 8 publications

References 8 publications

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

Acquisition of antibodies that block Plasmodium falciparum adhesion to placental receptor chondroitin sulfate A with increasing gravidity in Malian women

Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for a placental malaria vaccine

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