Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria

Chiu, Chris Y.H., Healer, Julie, Thompson, Jennifer K., Chen, Lin, Kaul, Aiki, Savergave, Laxman, Raghuwanshi, Arjun, Suen, Connie S.N. Li Wai, Siba, Peter M., Schofield, Louis, Mueller, Ivo, Cowman, Alan F., and Hansen, Diana S. (2014) Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria. Frontiers In Microbiology, 5. 314. pp. 1-8.

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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.

Item ID: 36241
Item Type: Article (Research - C1)
ISSN: 1664-302X
Keywords: malaria, Plasmodium falciparum, reticulocyte binding protein homolog 5, antibodies, immunity
Additional Information:

© 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.

Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC IRIISS Grant, NHMRC Project Grant 1031212
Date Deposited: 12 Nov 2014 12:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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