Antibodies to the Plasmodium falciparum proteins MSPDBL1 and MSPDBL2 opsonize merozoites, inhibit parasite growth, and predict protection from clinical malaria

Chiu, Chris Y.H., Hodder, Anthony N., Lin, Clara S., Hill, Danika L., Suen, Connie S.N. Li Wai, Schofield, Louis, Siba, Peter M., Mueller, Ivo, Cowman, Alan F., and Hansen, Diana S. (2015) Antibodies to the Plasmodium falciparum proteins MSPDBL1 and MSPDBL2 opsonize merozoites, inhibit parasite growth, and predict protection from clinical malaria. Journal of Infectious Diseases, 212 (3). pp. 406-415.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: http://dx.doi.org/10.1093/infdis/jiv057
 
23
12


Abstract

Increasing evidence suggests that antibodies against merozoite surface proteins (MSPs) play an important role in clinical immunity to malaria. Two unusual members of the MSP-3 family, merozoite surface protein duffy binding-like (MSPDBL)1 and MSPDBL2, have been shown to be extrinsically associated to MSP-1 on the parasite surface. In addition to a secreted polymorphic antigen associated with merozoite (SPAM) domain characteristic of MSP-3 family members, they also contain Duffy binding–like (DBL) domain and were found to bind to erythrocytes, suggesting that they play a role in parasite invasion. Antibody responses to these proteins were investigated in a treatment-reinfection study conducted in an endemic area of Papua New Guinea to determine their contribution to naturally acquired immunity. Antibodies to the SPAM domains of MSPDBL1 and MSPDBL2 as well as the DBL domain of MSPDBL1 were found to be associated with protection from Plasmodium falciparum clinical episodes. Moreover, affinity-purified anti-MSPDBL1 and MSPDBL2 were found to inhibit in vitro parasite growth and had strong merozoite opsonizing capacity, suggesting that protection targeting these antigens results from ≥2 distinct effector mechanisms. Together these results indicate that MSPDBL1 and MSPDBL2 are important targets of naturally acquired immunity and might constitute potential vaccine candidates.

Item ID: 42056
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: malaria, Plasmodium falciparum, MSPDBL1, MSPDBL2, antibodies, immunity
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Project grant 1031212, NHMRC Project grant 1058665
Date Deposited: 08 Dec 2015 18:07
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 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) > 920108 Immune System and Allergy @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
Downloads: Total: 12
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page