Аннотация
Иммунохроматография (ИХ) активно используется в современной практике серодиагностики – выявления в крови анти-
тел, специфичных к определённому патогену. Возможно несколько вариантов формирования в ходе ИХ меченых иммунных
комплексов, выбор между которыми требует экспериментальных оценок применительно к разным инфекциям. В статье
представлены разработка и сравнение трёх схем ИХ для выявления антител против возбудителя туляремии, отличающихся
по составу детектируемых комплексов: антиген – специфические антитела – меченый антиген (схема I); антиген – спец-
ифические антитела – меченые антивидовые антитела (схема II) и антивидовые антитела – специфические антитела –
меченый антиген (схема III). Для сравнения тест-систем использованы сыворотки крови больных туляремией, боррелиозом
и здоровых доноров (n=31). Для всех схем в выбранных условиях отсутствовали ложноположительные результаты, степени
выявления больных характеризовались рядом: схема II > схема III > схема I. Продолжительность ИХ для всех схем – 10 мин.
Annotation
Immunochromatography (IC) is widely used in modern practice of serodiagnostics, detection of antibodies specific to a certain
pathogen in the blood. Several variants of labeled immune complexes formation during IC are possible; the choice between them
requires experimental assessments in relation to different infections. The article presents the development and comparison of three
IC schemes for revealing antibodies against the causative agent of tularemia, differing in the composition of the detected complexes:
antigen – specific antibodies – labeled antigen (scheme I); antigen – specific antibodies – labeled anti-species antibodies (scheme II)
and anti-species antibodies – specific antibodies – labeled antigen (scheme III). Blood sera of patients with tularemia, borreliosis and
healthy donors (n=31) were applied to compare the test systems. For all schemes, there were no false positive results under the selected
conditions, and the revealing of sick patients was characterized by the following row: scheme II > scheme III > scheme I. The testing
time for all schemes was 10 min.
Key words: serodiagnostics; immunochromatography; test strips; labeled immune complexes; tularemia; Francisella tularensis
Список литературы
Л И Т Е РАТ У РА ( П П . 1 — 8 , 1 0 — 3 0 С М .
R E F E R E NC E S )
9. Горбатов А.А., Соловьёв П.В., Баранова Е.В., Титарёва Г.М.,
Куликалова Е.С., Бикетов С.Ф., Мазепа А.В. Сравнительное ис-
следование экспериментальных и коммерческих серологических
тестов для определения противотуляремийных антител у людей.
Клиническая лабораторная диагностика 2018; 63: 630-5. DOI:
10.18821/0869-2084-2018-63-10-630-635.
R E F E R E NC E S
1. Sjostedt A. Tularemia: History, epidemiology, pathogen physiology,
and clinical manifestations. Ann. N.-Y. Acad. Sci. 2007; 1105: 1–29.
DOI: 10.1196/annals.1409.009.
2. Wawszczak M., Banaszczak B., Rastawicki W. Tularaemia – A diagnostic
challenge. Ann. Agric. Environ. Med. 2022; 29: 12–21. DOI:
10.26444/aaem/139242.
3. Hepburn M.J., Simpson A.J.H. Tularemia: Current diagnosis and treatment
options. Expert Rev. Anti-Infect. Ther. 2008; 6: 231–40. DOI:
10.1586/14787210.6.2.231.
4. Banada P., Deshpande S., Chakravorty S., Russo R., Occi J., Meister G.
et al. Sensitive detection of Francisella tularensis directly from whole
blood by use of the GeneXpert system. J. Clin. Microbiol. 2017; 55:
291–301. DOI: 10.1128/JCM.01126-16.
5. Shchit I.Yu., Kudryavtseva T.Yu., Mokrievich A.N., Biketov S.F. Detection
of tularemia agent DNA by loop mediated isothermal amplification.
Mol. Gen. Microbiol. Virol. 2022; 37: 202–8. DOI: 10.3103/
S0891416822040085.
6. Ziegler I., Vollmar P., Knüpfer M., Braun P., Stoecker K. Reevaluating
limits of detection of 12 lateral flow immunoassays for the detection of
Yersinia pestis, Francisella tularensis, and Bacillus anthracis spores
using viable risk group-3 strains. J. Appl. Microbiol. 2020; 130: 1173-
80. DOI: 10.1111/jam.14863.
7. Splettstoesser W., Guglielmo-Viret V., Seibold E., Thullier P. Evaluation
of an immunochromatographic test for rapid and reliable serodiagnosis
of human tularemia and detection of Francisella tularensisspecific
antibodies in sera from different mammalian species. J. Clin.
Microbiol. 2010; 48: 1629-34. DOI: 10.1128/JCM.01475-09.
8. Chaignat V., Djordjevic-Spasic M., Ruettger A., Otto P., Klimpel D.,
Müller W. et al. Performance of seven serological assays for diagnosing
tularemia. BMC Infect. Dis. 2014; 14: 234. DOI: 10.1186/1471-
2334-14-234.
9. Gorbatov A.A., Soloviev P.V., Baranova E.V., Titareva G.M., Kulikalova
E.S., Biketov S.F., Mazepa A.V. Comparative study of experimental and
commercial serological tests for determining anti-tularemia antibodies in
humans. Klinicheskaya Laboratornaya Diagnostika. 2018; 63: 630–5.
DOI: 10.18821/0869-2084-2018-63-10-630-635. (in Russian)
10. Boehringer H.R., O’Farrell B.J. Lateral flow assays in infectious disease
diagnosis. Clin. Chem. 2022; 68: 52–8. DOI: 10.1093/clinchem/
hvab194.
11. Rosati G., Idili A., Parolo C., Fuentes-Chust C., Calucho E., Hu L.M. et
al. Nanodiagnostics to face SARS-CoV-2 and future pandemics: From
an idea to the market and beyond. ACS Nano. 2021; 15: 17137–49.
DOI: 10.1021/acsnano.1c06839.
12. Wang Z.X., Zhao J., Xu X.X., Guo L.L., Xu L.G., Sun M.Z. et al. An
overview for the nanoparticles-based quantitative lateral flow assay.
Small Methods. 2022; 6: 2101143. DOI: 10.1002/smtd.202101143.
13. Abduljalil J.M. Laboratory diagnosis of SARS-CoV-2: Available approaches
and limitations. New Microbes New Infect. 2020; 36: 100713.
DOI: 10.1016/j.nmni.2020.100713:
14. Su Z., Dou W., Liu X., Ping J., Li D., Ying Y. et al. Nano‐labeled materials
as detection tags for signal amplification in immunochromatographic
assay. TrAC Trends Anal. Chem. 2022; 154: 116673. DOI:
10.1016/j.trac.2022.116673.
15. Zhu W., Meng K., Zhang Y., Bu Z., Zhao D., Meng G. Lateral flow assay
for the detection of African swine fever virus antibodies using gold
nanoparticle-labeled acid-treated p72. Front. Chem. 2022; 9: 804981.
DOI: 10.3389/fchem.2021.804981.
16. Zhang Y., Chen Y., He Y., Li Y., Zhang X., Liang J. et al. Development
of receptor binding domain-based double-antigen sandwich lateral
flow immunoassay for the detection and evaluation of SARS-CoV-2
neutralizing antibody in clinical sera samples compared with the conventional
virus neutralization test. Talanta. 2023; 255: 124200. DOI:
10.1016/j.talanta.2022.124200.
17. Sotnikov D.V., Byzova N.A., Zherdev A.V., Xu Y., Dzantiev B.B.
Comparison of three lateral flow immunoassay formats for the detection
of antibodies against the SARS-CoV-2 antigen. Biosensors. 2023;
13: 750. DOI: 10.3390/bios13070750.
18. Sotnikov D.V., Zherdev A.V., Dzantiev B.B. Theoretical and experimental
comparison of different formats of immunochromatographic
serodiagnostics. Sensors. 2018; 18: 36. DOI: 10.3390/s18010036.
19. Byzova N.A., Zherdev A.V., Gorbatov A.А., Shevyakov A.G., Biketov
S.F., Dzantiev B.B. Rapid detection of lipopolysaccharide and whole
cells of Francisella tularensis based on agglutination of antibody-coated
gold nanoparticles and colorimetric registration. Micromachines.
2022; 13: 2194. DOI: 10.3390/mi13122194.
20. Frens G. Controlled nucleation for the regulation of the particle size in
monodisperse gold suspensions. Nat. Phys. Sci. 1973; 241: 20–2. DOI:
10.1038/physci241020a0.
21. Byzova N.A., Zherdev A.V., Khlebtsov B.N., Burov A.M., Khlebtsov
N.G., Dzantiev B.B. Advantages of highly spherical gold nanoparticles
as labels for lateral flow immunoassay. Sensors. 2020; 20: 3608. DOI:
10.3390/s20123608.
22. Khlebtsov N.G., Dykman L.A. Optical properties and biomedical applications
of plasmonic nanoparticles. J. Quant. Spectr. Rad. Trans.
2010; 111: 1–35. DOI: 10.1016/j.jqsrt.2009.07.012.
23. Sotnikov D.V., Zherdev A.V., Dzantiev B.B. Lateral flow serodiagnosis
in the double‐antigen sandwich format: Theoretical consideration
and confirmation of advantages. Sensors. 2021; 21: 39. DOI: 10.3390/
s21010039.
24. Sotnikov D.V., Byzova N.A., Zherdev A.V., Dzantiev B.B. Ability
of antibodies immobilized on gold nanoparticles to bind small antigen
fluorescein. Int. J. Mol. Sci. 2023; 24: 16967. DOI: 10.3390/
ijms242316967.
25. Srivastav S., Dankov A., Adanalic M., Grzeschik R., Tran V., Pagel-
Wieder S. et al. Rapid and sensitive SERS-based lateral flow test for
SARS-CoV2-specific IgM/IgG antibodies. Anal. Chem. 2021; 93:
12391–9. DOI: 10.1021/acs.analchem.1c02305.
26. Sotnikov D.V., Zherdev A.V., Dzantiev B.B. Mathematical model of
serodiagnostic immunochromatographic assay. Anal. Chem. 2017; 89:
4419–27. DOI: 10.1021/acs.analchem.6b03635.
27. Wang C., Yang X., Gu B., Liu H., Zhou Z., Shi L. et al. Sensitive and
simultaneous detection of SARS-CoV-2-specific IgM/IgG using lateral
flow immunoassay based on dual-mode quantum dot nanobeads. Anal.
Chem. 2020; 92: 15542–9. DOI: 10.1021/acs.analchem.0c03484.
28. Peng T., Sui Z., Huang Z., Xie J., Wen K., Zhang Y. et al. Point-of-care
test system for detection of immunoglobulin-G and -M against nucleocapsid
protein and spike glycoprotein of SARS-CoV-2. Sens. Actuators
B Chem. 2021; 331: 129415. DOI: 10.1016/j.snb.2020.129415.
29. Liu H., Dai E., Xiao R., Zhou Z., Zhang M., Bai Z. et al. Development
of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive
detection of anti-SARS-CoV-2 IgM/IgG in clinical samples. Sens. Actuators
B Chem. 2021; 329: 129196. DOI: 10.1016/j.snb.2020.129196.
30. Zhou Y., Chen Y., Liu W., Fang H., Li X., Hou L. et al. Development
of a rapid and sensitive quantum dot nanobead-based double-antigen
sandwich lateral flow immunoassay and its clinical performance for the
detection of SARS-CoV-2 total antibodies. Sens. Actuators B Chem.
2021; 343: 130139. DOI: 10.1016/j.snb.2021.130139.