- 148 views
- 232 downloads
Characterisation of antibody cross-reactivity between Plasmodium vivax DBL proteins and Plasmodium falciparum VAR2CSA in sera from Colombian and Brazilian populations
-
- Author / Creator
- Mena Palacios, Angie Yarleidy
-
Background: Malaria in pregnancy (MiP) poses a significant risk to the mother and fetus, causing approximately 10,000 maternal deaths and 200,000 infant deaths each year. A vast majority of these deaths are attributed to the species Plasmodium falciparum. MiP can cause severe negative birth outcomes such as maternal anemia, stillbirth, intrauterine growth restriction, and low infant birth weight. During infection with P. falciparum, the parasite protein VAR2CSA is expressed on the surface of infected red blood cells which sequester in the placenta. In Africa, maternal antibodies against VAR2CSA are acquired after several infections with the parasite and these antibodies confer protection against placental malaria. In Colombia and Brazil, we observed that non-pregnant populations exposed to Plasmodium vivax have high levels of antibodies against VAR2CSA. These sera also have antibodies to PvDBPII, a merozoite protein from P. vivax, which shares a DBL domain similar to those in VAR2CSA. We showed that PvDBPII affinity-purified antibodies from human sera recognized VAR2CSA by ELISA, as well as a mouse monoclonal antibody (mAb 3D10) raised against PvDBPII, demonstrating cross-reactivity between these proteins. The purpose of this study was to identify which are the shared cross-reactive epitopes between the DBL proteins from P. vivax that contribute to the protective antibodies against P. falciparum VAR2CSA.
Methods: Sera from non-pregnant populations from areas of Colombia and Brazil endemic to P. falciparum and P. vivax were analyzed for reactivity against VAR2CSA, PvDBPII, SD1 and EBP2. Cross-reactivity to VAR2CSA was characterized by ELISA. PvDBPII and SD1-specific antibodies were affinity-purified from pooled human sera from Colombia and the functional activity of these antibodies was evaluated in the inhibition of binding assay (IBA).
Results: Our study population has high levels of antibodies against PvDBPII, SD1, EBP2, and VAR2CSA. I found significant correlations between the antibody levels to PvDBPII, SD1 and VAR2CSA, but no correlation between VAR2CSA and EBP2. PvDBPII and SD1-specific antibodies recognized VAR2CSA by ELISA. SD1 affinity-purified antibodies inhibited the parasite binding to CSA in the IBA.
Conclusions: The findings from this work identified the subdomain 1 from PvDBPII as the potential source for the cross-reactive antibodies with VAR2CSA. This work contributes to our understanding of a new mechanism for natural cross-species immune recognition. This knowledge can be applied to the development of vaccine to protect women against placental malaria. -
- Graduation date
- Fall 2019
-
- Type of Item
- Thesis
-
- Degree
- Master of Science
-
- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.