The Relationship between Anti-merozoite Antibodies and Incidence of Malaria: A Systematic Review and Meta-analysis

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Background:
One of the criteria to objectively prioritize merozoite antigens for malaria vaccine development is the demonstration that naturally acquired antibodies are associated with protection from malaria. However, published evidence of the protective effect of these antibodies is conflicting.

Methods and Findings:
We performed a systematic review with meta-analysis of prospective cohort studies examining the association between anti-merozoite immunoglobin (Ig) G responses and incidence of Plasmodium falciparum malaria. Two independent researchers searched six databases and identified 33 studies that met predefined inclusion and quality criteria, including a rigorous definition of symptomatic malaria. We found that only five studies were performed outside sub-Saharan Africa and that there was a deficiency in studies investigating antibodies to leading vaccine candidates merozoite surface protein (MSP)-1₄₂ and erythrocyte binding antigen (EBA)-175. Meta-analyses of most-studied antigens were conducted to obtain summary estimates of the association between antibodies and incidence of P. falciparum malaria. The largest effect was observed with IgG to MSP-3 C terminus and MSP-1₁₉ (responders versus nonresponders, 54%, 95% confidence interval [CI] [33%–68%] and 18% [4%–30%] relative reduction in risk, respectively) and there was evidence of a dose-response relationship. A tendency towards protective risk ratios (RR<1) was also observed for individual study estimates for apical membrane antigen (AMA)-1 and glutamate-rich protein (GLURP)-R0. Pooled estimates showed limited evidence of a protective effect for antibodies to MSP-1 N-terminal regions or MSP-1-EGF (epidermal growth factor-like modules). There was no significant evidence for the protective effect for MSP-2 (responders versus nonresponders pooled RR, MSP-2_FC27 0.82, 95% CI 0.62–1.08, p = 0.16 and MSP-2_3D7 0.92, 95% CI 0.75–1.13, p = 0.43). Heterogeneity, in terms of clinical and methodological diversity between studies, was an important issue in the meta-analysis of IgG responses to merozoite antigens.

Conclusions:
These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans, and to help identify antigens that confer protection from malaria. Further prospective cohort studies that include a larger number of lead antigens and populations outside Africa are greatly needed to ensure generalizability of results. The reporting of results needs to be standardized to maximize comparability of studies. We therefore propose a set of guidelines to facilitate the uniform reporting of malaria immuno-epidemiology observational studies.

: Please see later in the article for the Editors' Summary

Vyšlo v časopise: The Relationship between Anti-merozoite Antibodies and Incidence of Malaria: A Systematic Review and Meta-analysis. PLoS Med 7(1): e32767. doi:10.1371/journal.pmed.1000218
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000218

Souhrn

Zdroje

1. MarshK

KinyanjuiS

2006 Immune effector mechanisms in malaria. Parasite Immunol 28 51 60

2. CohenS

McGI

CarringtonS

1961 Gamma-globulin and acquired immunity to human malaria. Nature 192 733 737

3. SabchareonA

BurnoufT

OuattaraD

AttanathP

Bouharoun-TayounH

1991 Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 45 297 308

4. CohenS

ButcherGA

CrandallRB

1969 Action of malarial antibody in vitro. Nature 223 368 371

5. BrownGV

AndersRF

MitchellGF

HeywoodPF

1982 Target antigens of purified human immunoglobulins which inhibit growth of Plasmodium falciparum in vitro. Nature 297 591 593

6. McCallumFJ

PerssonKE

MugyenyiCK

FowkesFJ

SimpsonJA

2008 Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum. PLoS One 3 e3571 doi:10.1371/journal.pone.0003571

7. Bouharoun-TayounH

AttanathP

SabchareonA

ChongsuphajaisiddhiT

DruilheP

1990 Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med 172 1633 1641

8. HodderAN

CrewtherPE

AndersRF

2001 Specificity of the protective antibody response to apical membrane antigen 1. Infect Immun 69 3286 3294

9. GaurD

MayerDC

MillerLH

2004 Parasite ligand-host receptor interactions during invasion of erythrocytes by Plasmodium merozoites. Int J Parasitol 34 1413 1429

10. O'DonnellRA

de Koning-WardTF

BurtRA

BockarieM

ReederJC

2001 Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria. J Exp Med 193 1403 1412

11. ClarkJT

DonachieS

AnandR

WilsonCF

HeidrichHG

1989 46–53 kilodalton glycoprotein from the surface of Plasmodium falciparum merozoites. Mol Biochem Parasitol 32 15 24

12. OeuvrayC

Bouharoun-TayounH

Gras-MasseH

BottiusE

KaidohT

1994 Merozoite surface protein-3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes. Blood 84 1594 1602

13. TheisenM

SoeS

OeuvrayC

ThomasAW

VuustJ

1998 The glutamate-rich protein (GLURP) of Plasmodium falciparum is a target for antibody-dependent monocyte-mediated inhibition of parasite growth in vitro. Infect Immun 66 11 17

14. DuttaS

HaynesJD

MochJK

BarbosaA

LanarDE

2003 Invasion-inhibitory antibodies inhibit proteolytic processing of apical membrane antigen 1 of Plasmodium falciparum merozoites. Proc Natl Acad Sci USA 100 12295 12300

15. PerssonKE

McCallumFJ

ReilingL

ListerNA

StubbsJ

2008 Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. J Clin Invest 118 342 351

16. CowmanAF

CrabbBS

2006 Invasion of red blood cells by malaria parasites. Cell 124 755 766

17. RichardsJS

BeesonJG

2009 The future for blood-stage vaccines against malaria. Immunol Cell Biol 87 377 390

18. GuptaS

SnowRW

DonnellyCA

MarshK

NewboldC

1999 Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 5 340 343

19. StroupDF

BerlinJA

MortonSC

OlkinI

WilliamsonGD

2000 Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283 2008 2012

20. World Health Organization 1990 Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg 84 Suppl 2 1 65

21. World Health Organization 2000 Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg 94 Suppl 1 S1 S90

22. EggerM

SmithGD

PhillipsAN

1997 Meta-analysis: principles and procedures. BMJ 315 1533 1537

23. ZhangJ

YuKF

1998 What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280 1690 1691

24. HigginsJP

ThompsonSG

DeeksJJ

AltmanDG

2003 Measuring inconsistency in meta-analyses. BMJ 327 557 560

25. IoannidisJP

PatsopoulosNA

EvangelouE

2007 Uncertainty in heterogeneity estimates in meta-analyses. BMJ 335 914 916

26. SterneJA

EggerM

2001 Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 54 1046 1055

27. EggerM

Davey SmithG

SchneiderM

MinderC

1997 Bias in meta-analysis detected by a simple, graphical test. BMJ 315 629 634

28. MeraldiV

NebieI

TionoAB

DialloD

SanogoE

2004 Natural antibody response to Plasmodium falciparum Exp-1, MSP-3 and GLURP long synthetic peptides and association with protection. Parasite Immunol 26 265 272

29. NebieI

DiarraA

OuedraogoA

SoulamaI

BougoumaEC

2008 Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun 76 759 766

30. NebieI

TionoAB

DialloDA

SamandoulougouS

DiarraA

2008 Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria? Trop Med Int Health 13 229 237

31. ConwayDJ

CavanaghDR

TanabeK

RoperC

MikesZS

2000 A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nat Med 6 689 692

32. PolleySD

TettehKK

CavanaghDR

PearceRJ

LloydJM

2003 Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria. Infect Immun 71 1833 1842

33. MetzgerWG

OkenuDM

CavanaghDR

RobinsonJV

BojangKA

2003 Serum IgG3 to the Plasmodium falciparum merozoite surface protein 2 is strongly associated with a reduced prospective risk of malaria. Parasite Immunol 25 307 312

34. PolleySD

TettehKK

LloydJM

AkpoghenetaOJ

GreenwoodBM

2007 Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection. J Infect Dis 195 279 287

35. DziegielM

RoweP

BennettS

AllenSJ

OlerupO

1993 Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children. Infect Immun 61 103 108

36. EganAF

MorrisJ

BarnishG

AllenS

GreenwoodBM

1996 Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J Infect Dis 173 765 769

37. TaylorRR

AllenSJ

GreenwoodBM

RileyEM

1998 IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. Am J Trop Med Hyg 58 406 413

38. OkenuDM

RileyEM

BickleQD

AgomoPU

BarbosaA

2000 Analysis of human antibodies to erythrocyte binding antigen 175 of Plasmodium falciparum. Infect Immun 68 5559 5566

39. OkechBA

CorranPH

ToddJ

Joynson-HicksA

UthaipibullC

2004 Fine specificity of serum antibodies to Plasmodium falciparum merozoite surface protein, PfMSP-1(19), predicts protection from malaria infection and high-density parasitemia. Infect Immun 72 1557 1567

40. GrayJC

CorranPH

MangiaE

GauntMW

LiQ

2007 Profiling the antibody immune response against blood stage malaria vaccine candidates. Clin Chem 53 1244 1253

41. DodooD

TheanderTG

KurtzhalsJA

KoramK

RileyE

1999 Levels of antibody to conserved parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malaria. Infect Immun 67 2131 2137

42. DodooD

TheisenM

KurtzhalsJA

AkanmoriBD

KoramKA

2000 Naturally acquired antibodies to the glutamate-rich protein are associated with protection against Plasmodium falciparum malaria. J Infect Dis 181 1202 1205

43. CavanaghDR

DodooD

HviidL

KurtzhalsJA

TheanderTG

2004 Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria. Infect Immun 72 6492 6502

44. DodooD

AikinsA

Asamoah KusiK

LampteyH

RemarqueE

2008 Cohort study of the association of antibody levels to AMA1, MSP119, MSP3 and GLURP with protection from clinical malaria in Ghanaian children. Malar J 7 142

45. PolleySD

MwangiT

KockenCH

ThomasAW

DuttaS

2004 Human antibodies to recombinant protein constructs of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) and their associations with protection from malaria. Vaccine 23 718 728

46. PolleySD

ConwayDJ

CavanaghDR

McBrideJS

LoweBS

2006 High levels of serum antibodies to merozoite surface protein 2 of Plasmodium falciparum are associated with reduced risk of clinical malaria in coastal Kenya. Vaccine 24 4233 4246

47. OsierFH

PolleySD

MwangiT

LoweB

ConwayDJ

2007 Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3. Parasite Immunol 29 387 394

48. Al-YamanF

GentonB

AndersR

TaraikaJ

GinnyM

1995 Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria. Parasite Immunol 17 493 501

49. Al-YamanF

GentonB

KramerK

ChangS

HuiG

1996 Assessment of the role of naturally acquired antibody levels to Plasmodium falciparum merozoite surface protein-1 in protecting Papa New Guinean children from malaria morbidity. Am J Trop Med Hyg 54 443 448

50. PerrautR

MarramaL

DioufB

SokhnaC

TallA

2005 Antibodies to the conserved C-terminal domain of the Plasmodium falciparum merozoite surface protein 1 and to the merozoite extract and their relationship with in vitro inhibitory antibodies and protection against clinical malaria in a Senegalese village. J Infect Dis 191 264 271

51. LusinguJP

VestergaardLS

AlifrangisM

MmbandoBP

TheisenM

2005 Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission. Malar J 4 48

52. JohnCC

O'DonnellRA

SumbaPO

MoormannAM

de Koning-WardTF

2004 Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa. J Immunol 173 666 672

53. JohnCC

MoormannAM

PregibonDC

SumbaPO

McHughMM

2005 Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. Am J Trop Med Hyg 73 222 228

54. TolleR

FruhK

DoumboO

KoitaO

N'DiayeM

1993 A prospective study of the association between the human humoral immune response to Plasmodium falciparum blood stage antigen gp190 and control of malarial infections. Infect Immun 61 40 47

55. StanisicDI

RichardsJS

McCallumFJ

MichonP

KingCL

2009 IgG subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun 77 1165 1174

56. PerrautR

MarramaL

DioufB

FontenilleD

TallA

2003 Distinct surrogate markers for protection against Plasmodium falciparum infection and clinical malaria identified in a Senegalese community after radical drug cure. J Infect Dis 188 1940 1950

57. WangL

RichieTL

StowersA

NhanDH

CoppelRL

2001 Naturally acquired antibody responses to Plasmodium falciparum merozoite surface protein 4 in a population living in an area of endemicity in Vietnam. Infect Immun 69 4390 4397

58. ScopelKK

da Silva-NunesM

MalafronteRS

BragaEM

FerreiraMU

2007 Variant-specific antibodies to merozoite surface protein 2 and clinical expression of Plasmodium falciparum malaria in rural Amazonians. Am J Trop Med Hyg 76 1084 1091

59. OsierFH

FeganG

PolleySD

MurungiL

VerraF

2008 Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect Immun 76 2240 2248

60. SarrJB

PelleauS

TolyC

GuitardJ

KonateL

2006 Impact of red blood cell polymorphisms on the antibody response to Plasmodium falciparum in Senegal. Microbes Infect 8 1260 1268

61. KoussisK

Withers-MartinezC

YeohS

ChildM

HackettF

2009 A multifunctional serine protease primes the malaria parasite for red blood cell invasion. Embo J 28 725 735

62. HuberW

FelgerI

MatileH

LippsHJ

SteigerS

1997 Limited sequence polymorphism in the Plasmodium falciparum merozoite surface protein 3. Mol Biochem Parasitol 87 231 234

63. HuJ

ChenZ

GuJ

WanM

ShenQ

2008 Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults. PLoS One 3 e1952 doi:10.1371/journal.pone.0001952

64. MalkinE

HuJ

LiZ

ChenZ

BiX

2008 A phase 1 trial of PfCP2.9: an AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria. Vaccine 26 6864 6873

65. OgutuBR

ApolloOJ

McKinneyD

OkothW

SianglaJ

2009 Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS ONE 4 e4708 doi:10.1371/journal.pone.0004708

66. MoherD

FortinP

JadadAR

JuniP

KlassenT

1996 Completeness of reporting of trials published in languages other than English: implications for conduct and reporting of systematic reviews. Lancet 347 363 366

67. RoussilhonC

OeuvrayC

Muller-GrafC

TallA

RogierC

2007 Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLoS Med 4 e320 doi:10.1371/journal.pmed.0040320

68. MabundaS

AponteJJ

TiagoA

AlonsoP

2009 A country-wide malaria survey in Mozambique. II. Malaria attributable proportion of fever and establishment of malaria case definition in children across different epidemiological settings. Malar J 8 74

69. MwangiTW

RossA

SnowRW

MarshK

2005 Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis 191 1932 1939

70. SmithT

SchellenbergJA

HayesR

1994 Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med 13 2345 2358

71. BejonP

WarimweG

MackintoshCL

MackinnonMJ

KinyanjuiSM

2009 Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun 77 1917 1923

72. EganAF

BurghausP

DruilheP

HolderAA

RileyEM

1999 Human antibodies to the 19kDa C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 inhibit parasite growth in vitro. Parasite Immunol 21 133 139

73. VandenbrouckeJP

von ElmE

AltmanDG

GotzschePC

MulrowCD

2007 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Ann Intern Med 147 W163 194

74. von ElmE

AltmanDG

EggerM

PocockSJ

GotzschePC

2007 The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370 1453 1457