Anti-MSP11 IgG inhibits Plasmodium falciparum merozoite invasion into erythrocytes in vitro. (April 2019)

• Record Type: Journal Article
• Authors: Tohmoto, Tatsuhiro; Takashima, Eizo; Takeo, Satoru; Morita, Masayuki; Nagaoka, Hikaru; Udomsangpetch, Rachanee; Sattabongkot, Jetsumon; Ishino, Tomoko; Torii, Motomi; Tsuboi, Takafumi
• Is Part Of: Parasitology international. Volume 69(2019)
• Page Start: 25
• Page End: 29
• Publication Date: 2019-04
• Subjects: Blood-stage vaccine -- Malaria -- MSP11 -- Plasmodium falciparum -- Rhoptry -- Thailand; ADCI antibody dependent cellular inhibition -- GIA growth inhibition activity -- WGCFS wheat germ cell-free system; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2018.10.012
• Languages: English
• ISSNs: 1383-5769

Abstract

Abstract: Merozoite surface proteins (MSPs) are considered as promising blood-stage malaria vaccine candidates. MSP3 has long been evaluated for its vaccine candidacy, however, the candidacy of other members of MSP3 family is insufficiently characterized. Here, we investigated Plasmodium falciparum MSP11 (PF3D7_1036000), a member of the MSP3 family, for its potential as a blood-stage vaccine candidate. The full-length protein (MSP11-FL) as well as the N-terminal half-MSP11 (MSP11-N), known to be unique among the MSP3 family members, were expressed by wheat germ cell-free system, and used to raise antibodies in rabbit. Immunoblot analysis of schizont lysates probed with anti-MSP11-N antibodies detected double bands at approximately 40 and 60 kDa, consistent with the previous report thus confirming antibodies specificity. However, inconsistent with previously reported merozoite's surface localization, immunofluorescence assay (IFA) revealed that MSP11 likely localizes to rhoptry neck of merozoites in mature schizonts. After invasion, MSP11 localized to parasitophorous vacuole and thereafter in Maurer's clefts in trophozoites. Anti-MSP11-FL antibody levels were significantly higher in asymptomatic than symptomatic P. falciparum cases in malaria low endemic Thailand. This reconfirmed that anti-MSP11 antibodies play an important role in protection against clinical malaria, as previously reported. Furthermore, in vitro growth inhibition assay revealed that anti-MSP11-FL rabbit antibodies biologically function by inhibiting merozoite invasion of erythrocytes. These findings further support the vaccine candidacy of MSP11. Highlights: MSP11 localizes to the merozoite's rhoptry neck and not on the surface. Antibodies to MSP11 were higher in asymptomatic than symptomatic cases in Thailand. Rabbit antibodies against MSP11 inhibit merozoite invasion of erythrocytes in vitro .