Naturally acquired immune responses to P. vivax merozoite surface protein 3α and merozoite surface protein 9 are associated with reduced risk of P. vivax malaria in young Papua New Guinean children.
BACKGROUND
Plasmodium vivax is the most geographically widespread human malaria parasite. Cohort studies in Papua New Guinea have identified a rapid onset of immunity against vivax-malaria in children living in highly endemic areas. Although numerous P. vivax merozoite antigens are targets of naturally acquired antibodies, the role of many of these antibodies in protective immunity is yet unknown.


RESULTS
In a cohort of children aged 1-3 years, antibodies to different regions of Merozoite Surface Protein 3α (PvMSP3α) and Merozoite Surface Protein 9 (PvMSP9) were measured and related to prospective risk of P. vivax malaria during 16 months of active follow-up. Overall, there was a low prevalence of antibodies to PvMSP3α and PvMSP9 proteins (9-65%). Antibodies to the PvMSP3α N-terminal, Block I and Block II regions increased significantly with age while antibodies to the PvMSP3α Block I and PvMSP9 N-terminal regions were positively associated with concurrent P. vivax infection. Independent of exposure (defined as the number of genetically distinct blood-stage infection acquired over time (molFOB)) and age, antibodies specific to both PvMSP3α Block II (adjusted incidence ratio (aIRR) = 0.59, p = 0.011) and PvMSP9 N-terminus (aIRR = 0.68, p = 0.035) were associated with protection against clinical P. vivax malaria. This protection was most pronounced against high-density infections. For PvMSP3α Block II, the effect was stronger with higher levels of antibodies.


CONCLUSIONS
These results indicate that PvMSP3α Block II and PvMSP9 N-terminus should be further investigated for their potential as P. vivax vaccine antigens. Controlling for molFOB assures that the observed associations are not confounded by individual differences in exposure.
Walter and Eliza Hall Institute, Parkville, Australia ; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
Danielle I
DI
Stanisic
Sarah
S
Javati
Benson
B
Kiniboro
Enmoore
E
Lin
Jianlin
J
Jiang
Balwan
B
Singh
Esmeralda V S
EV
Meyer
Peter
P
Siba
Cristian
C
Koepfli
Ingrid
I
Felger
Mary R
MR
Galinski
Ivo
I
Mueller
D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D010219:Papua New Guinea / Q000453:epidemiology; D010966:Plasmodium vivax / Q000276:immunology* / Q000472:pathogenicity*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan