Table 1 Antigen characteristic list
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 | |||
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 | |||
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 | |
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 | |
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 | |
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 | |
Diphtheria | Diphtheria toxoid | Dip tox | Immunity | Vaccine acquired immunity | 123.7 | 0.01 IU, 5PL | List Labs (Campbell, CA) | None | 60 | pH 5 | |||
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 | |
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 | |
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 | |
Measles virus | whole virus | wMeV | Vaccination or historical exposure | Vaccine acquired immunity or natural infection. | 215 | 153 mIU, 5PL | Zeptometrix (Buffalo, NY) | None | 150 | ||||
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 | |
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |||
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 | |
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 | ||
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 | ||
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 | |
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 | |
Tetanus | Tetanus toxoid | Tet tox | Immunity | Vaccine acquired immunity. | 30.6 | 0.01 IU, 5PL | List Labs (Campbell, CA) | None | 12.5 | pH 5 | |||
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 | |
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 | |
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 | |
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 |