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

BMC Medicine

Research Article

Arlene E. Dent¹  James W. Kazura¹  Kiprotich Chelimo²  Peter M. Siba³  Nadia Cross⁴  Damien R. Drew⁴  Salenna R. Elliott⁴  Ulrich Terheggen⁵  James G. Beeson⁶  Danny W. Wilson⁷  Ivo Mueller⁸  Anthony N. Hodder⁸ 

[1] Case Western Reserve University, Cleveland, Ohio, USA;Kenya Medical Research Institute, Kisian, Kenya;Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea;The Burnet Institute of Medical Research and Public Health, 85 Commercial Road, 3004, Melbourne, Victoria, Australia;The Burnet Institute of Medical Research and Public Health, 85 Commercial Road, 3004, Melbourne, Victoria, Australia;Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia;The Burnet Institute of Medical Research and Public Health, 85 Commercial Road, 3004, Melbourne, Victoria, Australia;Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia;Department of Microbiology, Monash University, Clayton, Victoria, Australia;The Burnet Institute of Medical Research and Public Health, 85 Commercial Road, 3004, Melbourne, Victoria, Australia;Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia;Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;

关键词: Plasmodium falciparum;    Malaria;    Vaccines;    Apical membrane antigen 1;    Antibodies;    Immunity;   

DOI  :  10.1186/s12916-016-0691-6

 received in 2016-04-06, accepted in 2016-09-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsP. 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.ResultsWe 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.ConclusionsThese 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.

【 授权许可】

CC BY   
© The Author(s). 2016