Genetic Mapping Identifies Novel Highly Protective Antigens for an Apicomplexan Parasite
Apicomplexan parasites are responsible for a myriad of diseases in humans and livestock; yet despite intensive effort, development of effective sub-unit vaccines remains a long-term goal. Antigenic complexity and our inability to identify protective antigens from the pool that induce response are serious challenges in the development of new vaccines. Using a combination of parasite genetics and selective barriers with population-based genetic fingerprinting, we have identified that immunity against the most important apicomplexan parasite of livestock (Eimeria spp.) was targeted against a few discrete regions of the genome. Herein we report the identification of six genomic regions and, within two of those loci, the identification of true protective antigens that confer immunity as sub-unit vaccines. The first of these is an Eimeria maxima homologue of apical membrane antigen-1 (AMA-1) and the second is a previously uncharacterised gene that we have termed ‘immune mapped protein-1’ (IMP-1). Significantly, homologues of the AMA-1 antigen are protective with a range of apicomplexan parasites including Plasmodium spp., which suggest that there may be some characteristic(s) of protective antigens shared across this diverse group of parasites. Interestingly, homologues of the IMP-1 antigen, which is protective against E. maxima infection, can be identified in Toxoplasma gondii and Neospora caninum. Overall, this study documents the discovery of novel protective antigens using a population-based genetic mapping approach allied with a protection-based screen of candidate genes. The identification of AMA-1 and IMP-1 represents a substantial step towards development of an effective anti-eimerian sub-unit vaccine and raises the possibility of identification of novel antigens for other apicomplexan parasites. Moreover, validation of the parasite genetics approach to identify effective antigens supports its adoption in other parasite systems where legitimate protective antigen identification is difficult.
Vyšlo v časopise:
Genetic Mapping Identifies Novel Highly Protective Antigens for an Apicomplexan Parasite. PLoS Pathog 7(2): e32767. doi:10.1371/journal.ppat.1001279
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001279
Souhrn
Apicomplexan parasites are responsible for a myriad of diseases in humans and livestock; yet despite intensive effort, development of effective sub-unit vaccines remains a long-term goal. Antigenic complexity and our inability to identify protective antigens from the pool that induce response are serious challenges in the development of new vaccines. Using a combination of parasite genetics and selective barriers with population-based genetic fingerprinting, we have identified that immunity against the most important apicomplexan parasite of livestock (Eimeria spp.) was targeted against a few discrete regions of the genome. Herein we report the identification of six genomic regions and, within two of those loci, the identification of true protective antigens that confer immunity as sub-unit vaccines. The first of these is an Eimeria maxima homologue of apical membrane antigen-1 (AMA-1) and the second is a previously uncharacterised gene that we have termed ‘immune mapped protein-1’ (IMP-1). Significantly, homologues of the AMA-1 antigen are protective with a range of apicomplexan parasites including Plasmodium spp., which suggest that there may be some characteristic(s) of protective antigens shared across this diverse group of parasites. Interestingly, homologues of the IMP-1 antigen, which is protective against E. maxima infection, can be identified in Toxoplasma gondii and Neospora caninum. Overall, this study documents the discovery of novel protective antigens using a population-based genetic mapping approach allied with a protection-based screen of candidate genes. The identification of AMA-1 and IMP-1 represents a substantial step towards development of an effective anti-eimerian sub-unit vaccine and raises the possibility of identification of novel antigens for other apicomplexan parasites. Moreover, validation of the parasite genetics approach to identify effective antigens supports its adoption in other parasite systems where legitimate protective antigen identification is difficult.
Zdroje
1. DuttaS
LeeSY
BatchelorAH
LanarDE
2007 Structural basis of antigenic escape of a malaria vaccine candidate. Proc Natl Acad Sci U S A 104 12488 12493
2. MelbyP
YangJ
ZhaoW
PerezL
ChengJ
2001 Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infect Immun 69 4719 4725
3. GodfrayHC
BeddingtonJR
CruteIR
HaddadL
LawrenceD
2010 Food security: the challenge of feeding 9 billion people. Science 327 812 818
4. PerryB
RandolphT
McDermottJ
SonesK
ThorntonP
2002 Investing in animal health research to alleviate poverty. ILRI (International Livestock Research Institute), Nairobi, Kenya
5. ShirleyMW
SmithAL
TomleyFM
2005 The biology of avian Eimeria with an emphasis on their control by vaccination. Adv Parasitol 60 285 330
6. BlakeDP
HeskethP
ArcherA
CarrollF
SmithAL
2004 Parasite genetics and the immune host: recombination between antigenic types of Eimeria maxima as an entree to the identification of protective antigens. Mol Biochem Parasitol 138 143 152
7. MartinelliA
CheesmanS
HuntP
CulletonR
RazaA
2005 A genetic approach to the de novo identification of targets of strain-specific immunity in malaria parasites. Proc Natl Acad Sci U S A 102 814 819
8. Maynard SmithJ
HaighJ
1974 The hitch-hiking effect of a favorable gene. Genet Res 23 23 35
9. ShirleyM
HarveyD
2000 A genetic linkage map of the apicomplexan protozoan parasite Eimeria tenella. Genome Res 10 1587 1593
10. ClarkJD
BillingtonK
BumsteadJM
OakesRD
SoonPE
2008 A toolbox facilitating stable transfection of Eimeria species. Mol Biochem Parasitol 162 77 86
11. RichieT
SaulA
2002 Progress and challenges for malaria vaccines. Nature 415 694 701
12. ZhangH
NishikawaY
YamagishiJ
ZhouJ
IkeharaY
2010 Neospora caninum: Application of apical membrane antigen 1 encapsulated in the oligomannose-coated liposomes for reduction of offspring mortality from infection in BALB/c mice. Exp Parasitol 125 130 136
13. KockenCH
van der WelAM
DubbeldMA
NarumDL
van de RijkeFM
1998 Precise timing of expression of a Plasmodium falciparum-derived transgene in Plasmodium berghei is a critical determinant of subsequent subcellular localization. J Biol Chem 273 15119 15124
14. DuttaS
DlugoszLS
ClaytonJW
PoolCD
HaynesJD
2010 Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1. Infect Immun 78 661 671
15. MuJ
MyersRA
JiangH
LiuS
RicklefsS
2010 Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet 42 268 271
16. LeeEC
YuD
Martinez de VelascoJ
TessarolloL
SwingDA
2001 A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73 56 65
17. KallL
KroghA
SonnhammerEL
2004 A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338 1027 1036
18. BendtsenJD
NielsenH
von HeijneG
BrunakS
2004 Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340 783 795
19. LetunicI
DoerksT
BorkP
2009 SMART 6: recent updates and new developments. Nucleic Acids Res 37 D229 232
20. AltschulSF
MaddenTL
SchafferAA
ZhangJ
ZhangZ
1997 Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 3389 3402
21. CheesmanS
O'MahonyE
PattaradilokratS
DegnanK
KnottS
2010 A single parasite gene determines strain-specific protective immunity against malaria: the role of the merozoite surface protein I. Int J Parasitol 40 951 961
22. BlakeDP
SmithAL
ShirleyMW
2003 Amplified fragment length polymorphism analyses of Eimeria spp.: an improved process for genetic studies of recombinant parasites. Parasitol Res 90 473 475
23. BlakeDP
HeskethP
ArcherA
ShirleyMW
SmithAL
2006 Eimeria maxima: the influence of host genotype on parasite reproduction as revealed by quantitative real-time PCR. Int J Parasitol 36 97 105
24. EckertJ
BraunR
ShirleyM
CoudertP
1995 Guidelines on techniques in coccidiosis research Brussels, Luxembourg European Commission
25. OsoegawaK
WoonPY
ZhaoB
FrengenE
TatenoM
1998 An improved approach for construction of bacterial artificial chromosome libraries. Genomics 52 1 8
26. ShirleyMW
KempDJ
PallisterJ
ProwseSJ
1990 A molecular karyotype of Eimeria tenella as revealed by contour-clamped homogeneous electric field gel electrophoresis. Mol Biochem Parasitol 38 169 173
27. VosP
HogersR
BleekerM
ReijansM
van de LeeT
1995 AFLP: a new technique for DNA fingerprinting. Nucleic Acids Res 23 4407 4414
28. RozenS
SkaletskyH
2000 Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132 365 386
29. ThompsonJD
GibsonTJ
PlewniakF
JeanmouginF
HigginsDG
1997 The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25 4876 4882
30. ThomasonL
CourtDL
BubunenkoM
CostantinoN
WilsonH
2007 Recombineering: genetic engineering in bacteria using homologous recombination. Curr Protoc Mol Biol Chapter 1 Unit 1. 16
31. SambrookJ
RussellD
2001 Molecular cloning: a laboratory manual New York, USA Cold Spring Harbour Laboratory Press
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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