Serological and molecular tools for the evaluation of malaria transmission blocking vaccines


Jones, SCP; (2015) Serological and molecular tools for the evaluation of malaria transmission blocking vaccines. PhD thesis, London School of Hygiene & Tropical Medicine. DOI: 10.17037/PUBS.02088685

[img]
Preview
Text - Accepted Version
License:

Download (4Mb) | Preview

Abstract

Malaria transmission blocking vaccines (TBV) have been prioritized as an intervention to facilitate malaria elimination, but tools are required to support roll-out and evaluation. This thesis presents research that aids development of pre-fertilization TBV candidate 10C (amino acids 159-428 of Pfs48/45). Gametocytes must be detected to identify the infectious reservoir and support mosquito infectivity studies. I proposed filter papers as a novel, cost effective, practical approach for collection and detection of mRNA in low density gametocytes. Comparing 3 filter papers, 2 RNA extraction methods and 2 molecular detection techniques, I concluded Whatman 903 and Whatman 3MM filter papers, combined with guanidine based nucleic acid extraction and detection using QT-NASBA, were operationally most appealing and most sensitive. To identify natural recognition to 10C and 230CMB (a vaccine candidate including amino acids 444-730 of Pfs230), cross sectional surveys were performed sampling school children (n=510) in 3 countries. I demonstrated naturally exposed individuals had antibodies against 10C and 230CMB which displayed age dependent acquisition (p<0.03). Supportive datasets demonstrated 10C and 230CMB antibodies are significantly associated with >90% transmission reducing activity (TRA) (p<0.003). To assess the TRA of 10C-immunized rats against genetically diverse parasites, I sampled venous blood from naturally infected participants in Burkina Faso (n=53), and performed direct membrane feeding assay combined with serum replacement using European control serum spiked with IgG from 10C vaccinated rats. I demonstrated 10C vaccine induced IgG significantly reduced transmission in 4/5 participants who were infectious and infected >2 mosquitoes. This resulted in 80.9-100% reduction in oocyst prevalence (p<0.042), and 85.2-100% reduction in oocyst density (p<0.023). My research identified an attractive combination of tools for detecting low density gametocytes to facilitate sampling in remote field settings. I advanced progress of 6 10C vaccine candidate by indicating antibodies are acquired following natural malaria exposure and are associated with functional TRA.

Item Type: Thesis
Thesis Type: Doctoral
Thesis Name: PhD
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Funders: The European FP7 Project
Grant number: 242079
Related URLs:
Copyright Holders: Sophie Jones
URI: http://researchonline.lshtm.ac.uk/id/eprint/2088685

Statistics


Download activity - last 12 months
Downloads since deposit
1,044Downloads
375Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item