Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines.

Details

Serval ID
serval:BIB_7A45803B7B0B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines.
Journal
BMC Medicine
Author(s)
Terheggen U., Drew D.R., Hodder A.N., Cross N.J., Mugyenyi C.K., Barry A.E., Anders R.F., Dutta S., Osier F.H., Elliott S.R., Senn N., Stanisic D.I., Marsh K., Siba P.M., Mueller I., Richards J.S., Beeson J.G.
ISSN
1741-7015 (Electronic)
ISSN-L
1741-7015
Publication state
Published
Issued date
2014
Volume
12
Number
1
Pages
183
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
BACKGROUND: Polymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.
METHODS: We aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.
RESULTS: We found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.
CONCLUSIONS: Antigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines.
Keywords
Adolescent, Adult, Alleles, Antibodies, Protozoan/immunology, Antigenic Variation, Antigens, Protozoan/immunology, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Humans, Kenya, Malaria Vaccines/genetics, Malaria Vaccines/immunology, Malaria, Falciparum/prevention & control, Membrane Proteins/immunology, Middle Aged, Papua New Guinea, Plasmodium falciparum/genetics, Plasmodium falciparum/immunology, Polymorphism, Genetic, Protozoan Proteins/immunology
Pubmed
Web of science
Open Access
Yes
Create date
09/01/2015 13:56
Last modification date
20/08/2019 14:36
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