Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria
- Author(s)
- Chiu, CY; Healer, J; Thompson, JK; Chen, L; Kaul, A; Savergave, L; Raghuwanshi, A; Li Wai Suen, CS; Siba, PM; Schofield, L; Mueller, I; Cowman, AF; Hansen, DS;
- Journal Title
- Frontiers in Microbiology
- Publication Type
- Journal Article
- Abstract
- Emerging evidence suggests that antibodies against merozoite proteins involved in Plasmodium falciparum invasion into the red blood cell (RBC) play an important role in clinical immunity to malaria. The protein family of parasite antigens known as P. falciparum reticulocyte binding protein-like homolog (PfRh) is required for RBC invasion. PfRh5 is the only member within the PfRh family that cannot be genetically deleted, suggesting it plays an essential role in parasite survival. This antigen forms a complex with the cysteine-rich P. falciparum Rh5 interacting protein (PfRipr), on the merozoite surface during RBC invasion. The PfRh5 ectodomain sequence and a C-terminal fragment of PfRipr were cloned and expressed in Escherichia coli and baculovirus-infected cells, respectively. Immunization of rabbits with these recombinant proteins induced antibodies able to inhibit growth of various P. falciparum strains. Antibody responses to these proteins were investigated in a treatment-re-infection study conducted in an endemic area of Papua New Guinea (PNG) to determine their contribution to naturally acquired immunity. Antibody titers to PfRh5 but not PfRipr showed strong association with protection against P. falciparum clinical episodes. When associations with time-to-first infection were analyzed, high antibody levels against PfRh5 were also found to be associated with protection from high-density infections but not from re-infection. Together these results indicate that PfRh5 is an important target of protective immunity and constitutes a promising vaccine candidate.
- Publisher
- Frontiers Media
- Research Division(s)
- Infection And Immunity
- Link To PubMed Central Version
- http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00314/full
- Publisher's Version
- https://doi.org/10.3389/fmicb.2014.00314
- Open Access at Publisher's Site
http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00314/full- Terms of Use/Rights Notice
- Copyright © 2014 Chiu, Healer, Thompson, Chen, Kaul, Savergave, Raghuvanshi, Li Wai Suen, Siba, Schofield, Mueller, Cowman and Hansen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Creation Date: 2014-07-31 12:19:42