Abstract
BackgroundAn effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a “gold standard” assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation. Therefore, there is currently no assurance that SMFA results are comparable between different studies.MethodsMouse anti-Pfs25 monoclonal antibody (mAb, 4B7 mAb), rat anti-Pfs48/45 mAb (85RF45.1 mAb) and a human polyclonal antibody (pAb) collected from a malaria-exposed adult were tested at the same concentrations (6–94 μg/mL for 4B7, 1.2–31.3 μg/mL for 85RF45.1 and 23–630 μg/mL for human pAb) in two laboratories following their own standardized SMFA protocols. The mAbs and pAb, previously shown to have strong inhibition activities in the SMFA, were tested at three or four concentrations in two or three independent assays in each laboratory, and percent inhibition in mean oocyst intensity relative to a control in the same feed was determined in each feeding experiment.ResultsBoth monoclonal and polyclonal antibodies dose-dependently reduced oocyst intensity in all experiments performed at the two test sites. In both laboratories, the inter-assay variability in percent inhibition in oocyst intensity decreased at higher levels of inhibition, regardless of which antibody was tested. At antibody concentrations that led to a >80 % reduction in oocyst numbers, the inter-laboratory variations were in the same range compared with the inter-assay variation observed within a single laboratory, and the differences in best estimates from multiple feeds between the two laboratories were <5 percentage points.ConclusionsThis study confirms previous reports that the precision of the SMFA increases with increasing percent inhibition. Moreover, the variation between the two laboratories is not greater than the variation observed within a laboratory. The findings of this study provide guidance for comparison of SMFA data from different laboratories.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1515-z) contains supplementary material, which is available to authorized users.
Highlights
An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development
The TropIQ method differs from the Radboudumc method in that the quality of the gametocyte culture is assessed based on microscopic examination of male exflagellation instead of determination of ookinete formation in a sample that is fed to mosquitoes a day before the actual feed
Similar correlations between mean oocysts and standard deviations or prevalence between the two laboratories Several groups have reported that the distribution of oocyst numbers is explained well by a negative binomial model [20, 25, 28, 29]
Summary
An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. Malaria mortality and morbidity have declined significantly in many parts of the world in the last 2 decades [1]. Despite this achievement, the World Health Organization estimated that there were still 438,000 deaths due to malaria in 2015, and that ~70 % of deaths occurred in children less than 5 years old [1]. SSM-VIMT have the potential to reduce malaria transmission from humans to mosquitoes for whole populations, and could be an important supplement to traditional controls in countries striving for malaria elimination [6,7,8]
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