Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum

Fiona J. McCallum, Kristina E.M. Persson, Cleopatra K. Mugyenyi, Freya J.I. Fowkes, Julie A. Simpson, Jack S. Richards, Thomas N. Williams, Kevin Marsh, James G. Beeson

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Abstract

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.

Original languageEnglish
Article numbere3571
JournalPLoS ONE
Volume3
Issue number10
DOIs
Publication statusPublished - 29 Oct 2008
Externally publishedYes

Cite this

McCallum, Fiona J. ; Persson, Kristina E.M. ; Mugyenyi, Cleopatra K. ; Fowkes, Freya J.I. ; Simpson, Julie A. ; Richards, Jack S. ; Williams, Thomas N. ; Marsh, Kevin ; Beeson, James G. / Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum. In: PLoS ONE. 2008 ; Vol. 3, No. 10.
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abstract = "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.",
author = "McCallum, {Fiona J.} and Persson, {Kristina E.M.} and Mugyenyi, {Cleopatra K.} and Fowkes, {Freya J.I.} and Simpson, {Julie A.} and Richards, {Jack S.} and Williams, {Thomas N.} and Kevin Marsh and Beeson, {James G.}",
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Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum. / McCallum, Fiona J.; Persson, Kristina E.M.; Mugyenyi, Cleopatra K.; Fowkes, Freya J.I.; Simpson, Julie A.; Richards, Jack S.; Williams, Thomas N.; Marsh, Kevin; Beeson, James G.

In: PLoS ONE, Vol. 3, No. 10, e3571, 29.10.2008.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum

AU - McCallum, Fiona J.

AU - Persson, Kristina E.M.

AU - Mugyenyi, Cleopatra K.

AU - Fowkes, Freya J.I.

AU - Simpson, Julie A.

AU - Richards, Jack S.

AU - Williams, Thomas N.

AU - Marsh, Kevin

AU - Beeson, James G.

PY - 2008/10/29

Y1 - 2008/10/29

N2 - 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.

AB - 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.

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