Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum.
BACKGROUND
Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood.


METHODS
We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42).


RESULTS
Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied.


CONCLUSIONS
Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria.
McCallum
Fiona J
FJ
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Persson
Kristina E M
KE
Mugyenyi
Cleopatra K
CK
Fowkes
Freya J I
FJ
Simpson
Julie A
JA
Richards
Jack S
JS
Williams
Thomas N
TN
Marsh
Kevin
K
Beeson
James G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007630:Kenya / Q000453:epidemiology; D008018:Life Cycle Stages / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D016036:Seroepidemiologic Studies; D055815:Young Adult
D000913:Antibodies, Protozoan