The Influence of Sub-Unit Composition and Expression System on the Functional Antibody Response in the Development of a VAR2CSA Based Plasmodium falciparum Placental Malaria Vaccine

PloS One
Morten A NielsenAli Salanti

Abstract

The disease caused by Plasmodium falciparum (Pf) involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. Placental malaria (PM) is one such manifestation in which Pf infected erythrocytes (IE) bind to chondroitin sulphate A (CSA) through expression of VAR2CSA, a parasite-derived antigen. Protection against PM is mediated by antibodies that inhibit binding of IE in the placental intervillous space. VAR2CSA is a large antigen incompatible with large scale recombinant protein expression. Vaccines based on sub-units encompassing the functionally constrained receptor-binding domains may, theoretically, circumvent polymorphisms, reduce the risk of escape-mutants and induce cross-reactive antibodies. However, the sub-unit composition and small differences in the borders, may lead to exposure of novel immuno-dominant antibody epitopes that lead to non-functional antibodies, and furthermore influence the folding, stability and yield of expression. Candidate antigens from the pre-clinical development expressed in High-Five insect cells using the baculovirus expression vector system were transitioned into the Drosophila Schneider-2 cell (S2) expression-system compliant with clinical developmen...Continue Reading

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Citations

Oct 16, 2015·Vaccine·Michal Fried, Patrick E Duffy
Apr 28, 2016·Journal of Nanobiotechnology·Susan ThraneAdam F Sander
May 18, 2016·The Journal of Infectious Diseases·Justin Yai Alamou DoritchamouPatrick E Duffy
Dec 3, 2016·Human Vaccines & Immunotherapeutics·Isabelle LegasteloisBettina Werle
Apr 25, 2017·Expert Review of Vaccines·Caroline PehrsonMorten A Nielsen
Jun 13, 2017·Nature Reviews. Microbiology·Mats WahlgrenReetesh R Akhouri
Jan 11, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Benjamin MordmüllerMorten A Nielsen
Apr 2, 2019·Frontiers in Endocrinology·Johanna SeitzUdo Rudolf Markert
May 8, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Nicaise Tuikue NdamPhilippe Deloron
Dec 2, 2020·Cancers·Peng LiuMichiel Stevens
Oct 18, 2020·Trends in Parasitology·Sedami Gnidehou, Stephanie K Yanow
Jan 22, 2021·Expert Review of Vaccines·Justin Yai Alamou DoritchamouNicaise Tuikue Ndam
Mar 16, 2021·Frontiers in Immunology·Benoît GamainMorten A Nielsen

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Methods Mentioned

BETA
flow-cytometry
transfection
glycosylation
ELISA
PCR
size exclusion chromatography
glycosylations
electrophoresis

Software Mentioned

Sigma Stat

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