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Anti-CelTOS Transmission Blocking Activity in vivo and in vitro against P. falciparum by Epitope-specific Monoclonal Antibodies
EP27090
Poster Title: Anti-CelTOS Transmission Blocking Activity in vivo and in vitro against P. falciparum by Epitope-specific Monoclonal Antibodies
Submitted on 08 Feb 2018
Author(s): Shulin Xu
Affiliations: COPH
This poster was presented at USF Health Research Day 2018 at USF Tampa campus
Poster Views: 403
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Poster Information
Abstract: Standard in vitro culture methods were used to produce mature gametocytes for the SMFA. The in vivo studies relied on an NF54 line carrying a luciferase-expressing cassette integrated in the genome. NSG mice treated with clodronate lipsome supported high-level engraftment of huRBC and can be infected by this P. falciparum luciferase reporter line, including development of mature gametocytes infectious for mosquitoes and leading to salivary gland sporozoites. This in vivo laboratory model permitted a highly sensitive transmission blocking assay to reliably quantify early oocyst development on day 22 post infection when stage V gametocytemia reached 0.07-0.18%. Mice were randomly divided into 4 groups and 60 min. before direct mosquito feed, each mouse in the antibody-treatment group received 16 mg/kg mAb in 200µl RPMI by iv injection and the blank control group received of equal volume RPMI. For the in vitro SMFA, 400 µg/ml of CelTOS mAb was added to gametocyte culture 60 min. prior to the mosquito feed. The presence of CelTOS mAb significantly inhibited oocyst development in mosquitoes in both in vivo and in vitro assays. Summary: The presence of CelTOS mAb significantly inhibited oocyst development in mosquitoes in both in vivo and in vitro assays. Importantly, the experimental results with an innovative in vivo humanized mouse model confirmed that circulating anti-CelTOS antibody effectively inhibits P. falciparum ookinete development to oocyst in mosquitoes. These results support the development of CelTOS as a transmission blocking vaccine.
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Tanner M, Greenwood B, Whitty CJ, Ansah EK, Price RN, Dondorp AM, von Seidlein L, Baird JK, Beeson JG, Fowkes FJ, Hemingway J, Marsh K, Osier F. 2015. Malaria eradication and elimination: views on how to translate a vision into reality. BMC Med 13: 167
WHO. 2016. World Malaria Report. Facts sheets, http://www.who.int/mediacentre/factsheets/fs094/en/ released in December 2016.
Bergmann-Leitner ES, Mease RM, De La Vega P, Savranskaya T, Polhemus M, Ockenhouse C, Angov E. 2010. Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei. PLoS One 5: e12294
Jimah JR, Salinas ND, Sala-Rabanal M, Jones NG, Sibley LD, Nichols CG, Schlesinger PH, Tolia NH. 2016. Malaria parasite CelTOS targets the inner leaflet
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