Table 1 Antigen characteristic list

From: Multiplex bead assays enable integrated serological surveillance and reveal cross-pathogen vulnerabilities in Zambezia Province, Mozambique

Pathogen

Antigen

Abbreviation

Rationale

Description

MFI cutoff

Cutoff determination method

Sensitivity in our study

Specificity in our study

Source of antigen

Tag

Coupling concentration (ug Ag/1.25e7 beads)

Coupling pH

References

Brugia malayi

SXP-1

Bm14

Exposure

Seroconversion to positive may take years even in an area of high ongoing transmission and there is evidence that antibodies are long-lived but will eventually go down following cure.

106.5

Mean + 3Stdev (CDC controls)

  

Recombinant CDC

GST

120

pH 7.2

39,40

Brugia malayi

Pepsin inhibitor analog AP-1

Bm33

Exposure

Seroconversion to positive may take years even in an area of high ongoing transmission and there is evidence that antibodies are long-lived but will eventually go down following cure.

375.2

Mean + 3Stdev (CDC controls)

  

Recombinant CDC

GST-His

20

pH 6 + 2 M Urea

41,42

Chlamydia trachomatis

Hypothetical, T3SS substrate

CT694

Historical exposure

Provides information about infection, exposure, cumulative infection

108

ROC

96%

97%

Recombinant CDC

GST

30

pH 7.2

43

Chlamydia trachomatis

pCT03 ORF

pgp3

Historical exposure

Provides information about infection, exposure, cumulative infection

212

ROC

93%

100%

Recombinant CDC

GST

120

pH 7.2

36

Cryptosporidium parvum

GP40/ 17-kDa antigen

Cp17

Exposure

Provides information about previous infection

72.5

ROC (Maximum Youden’s J)

100%

95%

Recombinant CDC

GST

6.8

pH 5

44,45,46

Cryptosporidium parvum

27-kDa antigen

Cp23

Exposure

Provides information about previous infection

830

ROC (Maximum Youden’s J)

100%

100%

Recombinant CDC

GST

12.5

pH 5

45,46,47

Diphtheria

Diphtheria toxoid

Dip tox

Immunity

Vaccine acquired immunity

123.7

0.01 IU, 5PL

  

List Labs (Campbell, CA)

None

60

pH 5

28,48

Expression tag control

Glutathione S-tranferase

GST

Control

Correct for background reactivity due to GST-tag

27

n/a negative control

n/a

n/a

CDC

GST

15

pH 5

49

Expression tag control

Glutathione S-tranferase

GST

Control

Correct for background reactivity due to GST-tag

93

n/a negative control

n/a

n/a

LSHTM

GST

58

pH 7.2

 

Giardia lamblia

Variant-specific surface protein AS8

VSP3

Exposure

Provides information about previous infection

72

ROC (Maximum Youden’s J)

100%

85%

CDC

GST

60

pH 5

50

Giardia lamblia

Variant-specific surface protein 42e

VSP5

Exposure

Provides information about previous infection

148

ROC (Maximum Youden’s J)

91%

100%

CDC

GST

60

pH 5

50

Measles virus

whole virus

wMeV

Vaccination or historical exposure

Vaccine acquired immunity or natural infection.

215

153 mIU, 5PL

  

Zeptometrix (Buffalo, NY)

None

150

 

29,51

Onchocerca volvulus

Ag16 Diagnostic antigen

OV16

Historical exposure

Marker of current or past infections. Antibody responses take at least 15 months to develop, so not immediate marker of infection. Detectable for several years after infections clear

422

ROC (Maximum Youden’s J)

91%

95%

Tom Nutman (National Institutes of Health, Bethesda, MD)

GST

30

pH 7.2

52

Plasmodium falciparum

Circumsporozoite protein full length

CSP

Liver stage exposure/ protection/RTS,S vaccination

Marker of recent exposure to infective mosquito bite; exposed to host immune system during journey to liver through skin delivery; validated

392.5

Maximum negative (LSHTM control)

  

Gennova

None

2.18

pH 7.2

22,53

Plasmodium falciparum

Early transcribed membrane protein 5 antigen 1 (N-terminal)

Etramp5 Ag1

Recent exposure

Marker of recent exposure based on blood stage infection; transmembrane protein exposed to immune system on iRBC surface and presumably following destruction; validated

168

Maximum negative (LSHTM control)

  

Recombinant LSHTM

GST

65

pH 7.2

22,25,54,55,56

Plasmodium falciparum

Gametocyte exported protein 18

Gexp18

Recent exposure

Marker of recent exposure based on blood stage infection; transmembrane protein exposed to immune system on iRBC surface and presumably following destruction; validated

632

Maximum negative (LSHTM control)

  

Recombinant LSHTM

GST

26.6

pH 7.2

22,25,56,57

Plasmodium falciparum

Glutamate rich protein region 2

GLURPR2

Historical exposure

Marker of historical exposure based on blood stage; validated

160.5

Maximum negative (LSHTM control)

  

Michael Theisen

His

0.084

pH 7.2

22,25,56,58

Plasmodium falciparum

Apical membrane antigen 1

PfAMA1

Historical exposure

Marker of historical exposure based on blood stage infection; released from apical tip during RBC invasion. Essential to invasion process; validated

143

Maximum negative (LSHTM control)

  

Recombinant LSHTM

His

7.7

pH 7.2

22,25,56,59,60

Plasmodium falciparum

19 kDa fragment of merozoite surface protein 1 molecule

PfMSP119

Historical exposure

Marker of historical exposure based on blood stage infection; major protein on surface of mz. Involved in invasion. Heterogeneous interaction with other merozoite proteins. Full function still to be determined. validated

405.9

FMM (LSHTM controls)

  

Recombinant LSHTM

GST

103

pH 7.2

22,25,56,60,61,62,63,64,65

Plasmodium falciparum

Reticulocyte Binding Protein-Like Homologue 4

Rh4.2

Medium term exposure and protection

Marker of recent exposure based on blood stage infection; part of invasion machinery. validated

448

Maximum negative (LSHTM control)

  

Recombinant LSHTM

GST

85

pH 7.2

22,66,67

Plasmodium malariae

19 kDa fragment of merozoite surface protein 1 molecule

PmMSP119

Historical exposure

Marker of historical exposure based on blood stage infection; based on Pf data

370

Maximum negative (LSHTM control)

  

Recombinant LSHTM

GST

1.15

pH 7.2

68,69

Plasmodium ovale

19 kDa fragment of merozoite surface protein 1 molecule

PoMSP119

Historical exposure

Marker of historical exposure based on blood stage infection; based on Pf data

373.5

Maximum negative (LSHTM control)

  

Recombinant LSHTM

GST

9.41

pH 7.2

68

Plasmodium vivax

Duffy binding protein RII

PvDBPRII

Exposure

Vivax invasion machinery component. Duffy binding protein/ligand. validated

534.3

Maximum negative (LSHTM control)

  

Chetan Chitnis, Pasteur

GST

2.23

pH 7.2

70,71,72

Plasmodium vivax

19 kDa fragment of merozoite surface protein 1 molecule

PvMSP119

Historical exposure

As for Pfalciparum. validated

550

Maximum negative (LSHTM control)

  

LSHTM

GST

380

pH 7.2

68

Plasmodium vivax

Reticulocyte-binding protein 2b

PvRBP2b

Exposure

Reticulocyte binding protein homologe. Part of invasion machinery. Validated

577

Maximum negative (LSHTM control)

  

Chetan Chitnis, Pasteur

GST

4.13

pH 7.2

70,73,74

Rubella virus

Whole virus

wRuV

Vaccination or historical exposure

Vaccine acquired immunity or natural infection.

255

9.36 IU, 5PL

  

Commercial

None

30

pH 7.2

29,51

SARS-CoV-2 Wuhan/L strain

Nucleocapsid protein

SARS2 NP

Exposure

Usually natural infection except in places were nucleocapsid is in vaccines.

614.8

Maximum negative (LSHTM control)

  

COVID-19 Protein Portal

His

3.4

pH 7.2

75,76

SARS-CoV-2 Wuhan/L strain

Spike glycoprotein S1 receptor-binding domain

SARS2 RBD

Vaccination or natural exposure

Vaccine acquired immunity or natural infection.

387.5

Maximum negative (LSHTM control)

  

Native Antigen Company

His

15

pH 7.2

75,76

Schistosoma mansoni

Soluble egg antigen

SEA

Historical exposure

Measures antibodies against scistosome eggs.

410

ROC (Maximum Youden’s J)

85%

98%

CDC

None

120

pH 7.2

77,78

Schistosoma mansoni

 

Sm25

Historical exposure

Measures antibodies against S. mansoni adult worms.

38.5

ROC (Maximum specificity)

75%

98%

Recombinant CDC

GST

12

pH 7.2

78,79,80

Strongyloides stercoralis

 

NIE

Exposure

High titers can be indicative of current chronic infection if individuals have never been treated.

526

ROC (Maximum Youden’s J)

81%

100%

Recombinant CDC

GST

20

pH 7.2 + 2 M Urea

81,82

Taenia solium

T. solium excretory secretory 33 kDa

ES33

Exposure

Antibodies are markers of exposure to tape worm.

22

ROC (Maximum specificity)

88%

100%

Recombinant CDC

GST

10

pH 5

83

Taenia solium

Cysticercosis marker

T24H

Exposure

Antibodies are markers of exposure to cysts.

103.5

ROC (Maximum specificity)

86%

100%

Recombinant CDC

GST

120

pH 5

84,85

Tetanus

Tetanus toxoid

Tet tox

Immunity

Vaccine acquired immunity.

30.6

0.01 IU, 5PL

  

List Labs (Campbell, CA)

None

12.5

pH 5

30,86

Treponema pallidum pertenue

Yaws

rp17

Historical exposure

Current infection or previous exposure to T. pallidum subsp pallidum (syphilis) or T. pallidum subsp pertenue (yaws). Marker of historical infection.

73.5

ROC (Maximum Youden’s J)

94%

95%

ViroGen (Boston, MA)

Beta galactosidase

15

pH 7.2

27

Treponema pallidum pertenue

Treponemal membrane protein A (Yaws)

TmpA

Recent exposure

Marker of current infection to T. pallidum subsp pallidum (syphilis) or T. pallidum subsp pertenue (yaws). Responses decline after treatment.

247

ROC (Maximum Youden’s J)

100%

96%

ViroGen (Boston, MA)

Beta galactosidase

30

pH 7.2

27,87

Cercopithecus aethiops

Uninfected Vero cell lysate

UnLys

Control

Identify and eliminate samples with high background for cell line used to produce viral antigens wMeV and RuV.

n/a

n/a negative control

n/a

n/a

CDC

n/a

150

7.2

15

Wuchereria bancrofti

Larval antigen

Wb123

exposure

Antibodies expressed by the L3 larval stage transmitted by mosquitoes

58.2

Mean  +3Stdev (CDC controls)

  

Tom Nutman (National Institutes of Health, Bethesda, MD)

GST

30

pH 7.2

88,89,90