Mathematical model for assessing the level of cross-immunity between strains of influenza virus subtype H3N2

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Abstract

Introduction. The WHO regularly updates influenza vaccine recommendations to maximize their match with circulating strains. Nevertheless, the effectiveness of the influenza A vaccine, specifically its H3N2 component, has been low for several seasons.

The aim of the study is to develop a mathematical model of cross-immunity based on the array of published WHO hemagglutination inhibition assay (HAI) data.

Materials and methods. In this study, a mathematical model was proposed, based on finding, using regression analysis, the dependence of HAI titers on substitutions in antigenic sites of sequences. The computer program we developed can process data (GISAID, NCBI, etc.) and create “real-time” databases according to the set tasks.

Results. Based on our research, an additional antigenic site F was identified. The difference in 1.6 times the adjusted R2, on subsets of viruses grown in cell culture and grown in chicken embryos, demonstrates the validity of our decision to divide the original data array by passage histories. We have introduced the concept of a degree of homology between two arbitrary strains, which takes the value of a function depending on the Hamming distance, and it has been shown that the regression results significantly depend on the choice of function. The provided analysis showed that the most significant antigenic sites are A, B, and E. The obtained results on predicted HAI titers showed a good enough result, comparable to similar work by our colleagues.

Conclusion. The proposed method could serve as a useful tool for future forecasts, with further study to confirm its sustainability.

About the authors

Marina N. Asatryan

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Author for correspondence.
Email: masatryan@gamaleya.org
ORCID iD: 0000-0001-6273-8615

PhD (Med.), senior researcher epidemiological cybernetics group of the Epidemiology Department

Russian Federation, 123098, Moscow

Boris I. Timofeev

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0001-7425-0457

PhD (Phys.-Mat.), senior researcher D.I. Ivanovsky Institute of Virology Division

Russian Federation, 123098, Moscow

Ilya S. Shmyr

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-8514-5174

researcher epidemiological cybernetics group of the Epidemiology Department

Russian Federation, 123098, Moscow

Karlen R. Khachatryan

National Research University Higher School of Economics

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-1934-532X

master's student

Russian Federation, 123458, Moscow

Dmitrii N. Shcherbinin

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-8518-1669

PhD (Biol.), researcher, Department of Genetics and Molecular Biology of Bacteria

Russian Federation, 123098, Moscow

Tatiana A. Timofeeva

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-8991-8525

PhD (Biol.), head of laboratory D.I. Ivanovsky Institute of Virology Division

Russian Federation, 123098, Moscow

Elita R. Gerasimuk

State University “Dubna”

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-7364-163X

PhD (Med.), Assoc. Prof.

Russian Federation, 141982, Dubna

Vaagn G. Agasaryan

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0009-0009-3824-7061

researcher epidemiological cybernetics group of the Epidemiology Department

Russian Federation, 123098, Moscow

Ivan F. Ershov

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-3333-5347

researcher epidemiological cybernetics group of the Epidemiology Department

Russian Federation, 123098, Moscow

Tatyana I. Shashkova

Artificial Intelligence Research Institute

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-8754-8727

PhD (Biol.), senior researcher Bioinformatics group

Russian Federation, 121170, Moscow

Olga L. Kardymon

Artificial Intelligence Research Institute

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-4827-8891

head of Bioinformatics research group

Russian Federation, 121170, Moscow

Nikita V. Ivanisenko

Artificial Intelligence Research Institute

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-0333-8117

PhD (Biol.), senior researcher Bioinformatics group

Russian Federation, 121170, Moscow

Tatyana A. Semenenko

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0002-6686-9011

D. Sci. (Med.), Prof., Full Member of RANS, head Department of Epidemiology

Russian Federation, 123098, Moscow

Boris S. Naroditsky

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0001-5522-8238

D. Sci. (Biol.), professor, Deputy Director for research D.I. Ivanovsky Institute of Virology Division

Russian Federation, 123098, Moscow

Denis Yu. Logunov

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org

D. Sci. (Biol.), Full Member of RAS, Deputy Director for research

Russian Federation, 123098, Moscow

Aleksander L. Gintsburg

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: masatryan@gamaleya.org
ORCID iD: 0000-0003-1769-5059

D. Sci. (Biol.), Prof., Full Member of RAS, Director

Russian Federation, 123098, Moscow

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Supplementary files

Supplementary Files
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2. Application
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3. Figure. Functions for evaluating the degree of homology.

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Copyright (c) 2023 Asatryan M.N., Timofeev B.I., Shmyr I.S., Khachatryan K.R., Shcherbinin D.N., Timofeeva T.A., Gerasimuk E.R., Agasaryan V.G., Ershov I.F., Shashkova T.I., Kardymon O.L., Ivanisenko N.V., Semenenko T.A., Naroditsky B.S., Logunov D.Y., Gintsburg A.L.

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