Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19) are associated with the protection of naturally exposed children against infection.
BACKGROUND
The 19 kDa C-terminal region of Plasmodium falciparum Merozoite Surface Protein-1 is a known target of naturally acquired humoral immunity and a malaria vaccine candidate. MSP-119 has four predominant haplotypes resulting in amino acid changes labelled EKNG, QKNG, QTSR and ETSR. IgG antibodies directed against all four variants have been detected, but it is not known if these variant specific antibodies are associated with haplotype-specific protection from infection.


METHODS
Blood samples from 201 healthy Kenyan adults and children who participated in a 12-week treatment time-to-infection study were evaluated. Venous blood drawn at baseline (week 0) was examined for functional and serologic antibodies to MSP-119 and MSP-142 variants. MSP-119 haplotypes were detected by a multiplex PCR assay at baseline and weekly throughout the study. Generalized linear models controlling for age, baseline MSP-119 haplotype and parasite density were used to determine the relationship between infecting P. falciparum MSP-119 haplotype and variant-specific antibodies.


RESULTS
A total of 964 infections resulting in 1,533 MSP-119 haplotypes detected were examined. The most common haplotypes were EKNG and QKNG, followed by ETSR and QTSR. Children had higher parasite densities, greater complexity of infection (>1 haplotype), and more frequent changes in haplotypes over time compared to adults. Infecting MSP-119 haplotype at baseline (week 0) had no influence on haplotypes detected over the subsequent 11 weeks among children or adults. Children but not adults with MSP-119 and some MSP-142 variant antibodies detected by serology at baseline had delayed time-to-infection. There was no significant association of variant-specific serology or functional antibodies at baseline with infecting haplotype at baseline or during 11 weeks of follow up among children or adults.


CONCLUSIONS
Variant transcending IgG antibodies to MSP-119 are associated with protection from infection in children, but not adults. These data suggest that inclusion of more than one MSP-119 variant may not be required in a malaria blood stage vaccine.
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA. arlene.dent@case.edu
Arlene E
AE
Dent
Ann M
AM
Moormann
Christopher T
CT
Yohn
Rhonda J
RJ
Kimmel
Peter O
PO
Sumba
John
J
Vulule
Carole A
CA
Long
David L
DL
Narum
Brendan S
BS
Crabb
James W
JW
Kazura
Daniel J
DJ
Tisch
D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood*; D002648:Child; D006239:Haplotypes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology* / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D010963:Plasmodium falciparum / Q000276:immunology*; D055815:Young Adult
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1