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BMC Medicine
Published in: BMC Medicine 1/2014

Open Access 01-12-2014 | Research article

Opsonic phagocytosis of Plasmodium falciparummerozoites: mechanism in human immunity and a correlate of protection against malaria

Authors: Faith HA Osier, Gaoqian Feng, Michelle J Boyle, Christine Langer, Jingling Zhou, Jack S Richards, Fiona J McCallum, Linda Reiling, Anthony Jaworowski, Robin F Anders, Kevin Marsh, James G Beeson

Published in: BMC Medicine | Issue 1/2014

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Abstract

Background

An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but critically important to advance the development of highly efficacious vaccines. Antibodies play a key role in acquired immunity, but the functional basis for their protective effect remains unclear. Furthermore, there is a strong need for immune correlates of protection against malaria to guide vaccine development.

Methods

Using a validated assay to measure opsonic phagocytosis of Plasmodium falciparum merozoites, we investigated the potential role of this functional activity in human immunity against clinical episodes of malaria in two independent cohorts (n = 109 and n = 287) experiencing differing levels of malaria transmission and evaluated its potential as a correlate of protection.

Results

Antibodies promoting opsonic phagocytosis of merozoites were cytophilic immunoglobulins (IgG1 and IgG3), induced monocyte activation and production of pro-inflammatory cytokines, and were directed against major merozoite surface proteins (MSPs). Consistent with protective immunity in humans, opsonizing antibodies were acquired with increasing age and malaria exposure, were boosted on re-infection, and levels were related to malaria transmission intensity. Opsonic phagocytosis was strongly associated with a reduced risk of clinical malaria in longitudinal studies in children with current or recent infections. In contrast, antibodies to the merozoite surface in standard immunoassays, or growth-inhibitory antibodies, were not significantly associated with protection. In multivariate analyses including several antibody responses, opsonic phagocytosis remained significantly associated with protection against malaria, highlighting its potential as a correlate of immunity. Furthermore, we demonstrate that human antibodies against MSP2 and MSP3 that are strongly associated with protection in this population are effective in opsonic phagocytosis of merozoites, providing a functional link between these antigen-specific responses and protection for the first time.

Conclusions

Opsonic phagocytosis of merozoites appears to be an important mechanism contributing to protective immunity in humans. The opsonic phagocytosis assay appears to be a strong correlate of protection against malaria, a valuable biomarker of immunity, and provides a much-needed new tool for assessing responses to blood-stage malaria vaccines and measuring immunity in populations.
Appendix
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Metadata
Title
Opsonic phagocytosis of Plasmodium falciparummerozoites: mechanism in human immunity and a correlate of protection against malaria
Authors
Faith HA Osier
Gaoqian Feng
Michelle J Boyle
Christine Langer
Jingling Zhou
Jack S Richards
Fiona J McCallum
Linda Reiling
Anthony Jaworowski
Robin F Anders
Kevin Marsh
James G Beeson
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2014
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-12-108

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