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BMC Medicine
Published in: BMC Medicine 1/2016

Open Access 01-12-2016 | Research article

A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens

Authors: Damien R. Drew, Danny W. Wilson, Salenna R. Elliott, Nadia Cross, Ulrich Terheggen, Anthony N. Hodder, Peter M. Siba, Kiprotich Chelimo, Arlene E. Dent, James W. Kazura, Ivo Mueller, James G. Beeson

Published in: BMC Medicine | Issue 1/2016

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Abstract

Background

The polymorphic nature of many malaria vaccine candidates presents major challenges to achieving highly efficacious vaccines. Presently, there is very little knowledge on the prevalence and patterns of functional immune responses to polymorphic vaccine candidates in populations to guide vaccine design. A leading polymorphic vaccine candidate against blood-stage Plasmodium falciparum is apical membrane antigen 1 (AMA1), which is essential for erythrocyte invasion. The importance of AMA1 as a target of acquired human inhibitory antibodies, their allele specificity and prevalence in populations is unknown, but crucial for vaccine design.

Methods

P. falciparum lines expressing different AMA1 alleles were genetically engineered and used to quantify functional antibodies from two malaria-exposed populations of adults and children. The acquisition of AMA1 antibodies was also detected using enzyme-linked immunosorbent assay (ELISA) and competition ELISA (using different AMA1 alleles) from the same populations.

Results

We found that AMA1 was a major target of naturally acquired invasion-inhibitory antibodies that were highly prevalent in malaria-endemic populations and showed a high degree of allele specificity. Significantly, the prevalence of inhibitory antibodies to different alleles varied substantially within populations and between geographic locations. Inhibitory antibodies to three specific alleles were highly prevalent (FVO and W2mef in Papua New Guinea; FVO and XIE in Kenya), identifying them for potential vaccine inclusion. Measurement of antibodies by standard or competition ELISA was not strongly predictive of allele-specific inhibitory antibodies. The patterns of allele-specific functional antibody responses detected with our novel assays may indicate that acquired immunity is elicited towards serotypes that are prevalent in each geographic location.

Conclusions

These findings provide new insights into the nature and acquisition of functional immunity to a polymorphic vaccine candidate and strategies to quantify functional immunity in populations to guide rational vaccine design.
Appendix
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Metadata
Title
A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens
Authors
Damien R. Drew
Danny W. Wilson
Salenna R. Elliott
Nadia Cross
Ulrich Terheggen
Anthony N. Hodder
Peter M. Siba
Kiprotich Chelimo
Arlene E. Dent
James W. Kazura
Ivo Mueller
James G. Beeson
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2016
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-016-0691-6

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