Biological properties of the recombinant influenza A/H1N1pdm09 virus expressing a fragment of the Streptococcus pneumoniae surface protein

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Abstract

BACKGROUND: Live influenza vaccine strains may serve as a promising system for the delivery of target antigens to the body because such a vaccine is administered intranasally and stimulates multiple chains of immunity against both the target pathogen and the influenza virus, a serious infection that causes significant socioeconomic damage worldwide each year.

AIM: The study was aimed to evaluate the biological properties of a recombinant live influenza vaccine strain of subtype A/H1N1pdm09 expressing a fragment of the Streptococcus pneumoniae Spr1875 surface protein.

MATERIALS AND METHODS: The A/H1N1pdm09 recombinant live influenza vaccine strain expressing a 69-amino-acid fragment of the S. pneumoniae surface protein Spr1875 as part of a chimeric hemagglutinin molecule was prepared by reverse genetics using an 8-plasmid system. The reproductive activity of the recombinant virus was studied in chicken embryos, whereas immunogenicity and protective efficiency were studied in Balb/C mice.

RESULTS: The recombinant influenza virus strain with hemagglutinin H1-Spr-69 demonstrated active reproduction in chicken embryos and retained the temperature-sensitive phenotypic trait of vaccine viruses. However, its growth in the respiratory tract of mice was limited compared with the original A/H1N1pdm09 vaccine virus. Intranasal administration of the recombinant H1-Spr strain to mice resulted in stimulation of virus-specific serum IgG antibody production comparable to that induced by the classic live influenza A/H1N1pdm09 vaccine. Furthermore, this strain induced an increase in IgG antibodies against the pneumococcal insertion Spr1875. Although the A/H1N1pdm09 variant was more effective than the chimeric H1-Spr virus in preventing weight loss in mice infected with mouse-adapted influenza A/California/07/09 (H1N1)pdm09 (H1N1)pdm09 virus, the titers of the challenge virus in the lungs of mice from both vaccine groups were significantly reduced compared with unvaccinated animals.

CONCLUSIONS: The results demonstrate the ability of the chimeric recombinant H1-Spr strain to stimulate protective immunity against influenza virus.

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About the authors

Yulia A. Desheva

Institute of Experimental Medicine; Saint Petersburg State University

Email: desheva@mail.ru
ORCID iD: 0000-0001-9794-3520
SPIN-code: 4881-3786

MD, Dr. Sci. (Medicine), Professor of the Department of Fundamental Problems in Medicine and Medical Technologies; Leading Research Associate of the Department of Virology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022; Saint Petersburg

Andrey R. Rekstin

Institute of Experimental Medicine

Email: arekstin@yandex.ru
ORCID iD: 0000-0003-2156-1635
SPIN-code: 5359-1516

Cand. Sci. (Biology), Leading Research Associate of the Department of Virology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Irina V. Mayorova

Institute of Experimental Medicine

Email: mayorovairina0248@gmail.com
ORCID iD: 0009-0009-5130-5000

Research Technician of the Department of Virology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Nina V. Kopylova

Institute of Experimental Medicine

Email: KNINA5485@gmail.com
ORCID iD: 0009-0004-1963-0333

Research Technician of the Department of Virology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Olga S. Kopteva

Institute of Experimental Medicine; Saint Petersburg State University

Email: olga.s.kopteva@yandex.ru
ORCID iD: 0000-0002-2645-3433
SPIN-code: 7630-3067

Research Associate at the world-class scientific center “Center for Personalized Medicine”, Postgraduate student

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022; Saint Petersburg

Daria S. Petrachkova

Institute of Experimental Medicine

Author for correspondence.
Email: ya.dashook@ya.ru
ORCID iD: 0009-0004-0045-4886
SPIN-code: 8464-2810

Research Technician of the Department of Virology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Polina A. Kudar

Institute of Experimental Medicine

Email: polina6226@mail.ru
ORCID iD: 0000-0002-3342-5828
SPIN-code: 9211-0537

Junior Research Associate at the world-class scientific center “Center for Personalized Medicine”

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Tatyana S. Kotomina

Institute of Experimental Medicine

Email: tstretiak@gmail.com
ORCID iD: 0000-0001-9999-089X
SPIN-code: 7613-9715

Research Associate at the Laboratory of Immunology and Prevention of Viral Infections of the A.A. Smorodintsev Virology Department

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Anastasia S. Matushkina

Institute of Experimental Medicine

Email: anastasiia.evsina@gmail.com
ORCID iD: 0000-0002-9045-0683
SPIN-code: 5437-8402

Research Associate at the A.A. Smorodintsev Virology Department

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Galina F. Leontieva

Institute of Experimental Medicine

Email: galeonte@yandex.ru
ORCID iD: 0000-0002-9876-6594
SPIN-code: 5204-9252

Cand. Sci. (Biology), Senior Research Associate at the world-class scientific center “Center for Personalized Medicine”, Senior Research Associate at the Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Tatyana A. Kramskaya

Institute of Experimental Medicine

Email: Tatyana.kramskaya@gmail.com
ORCID iD: 0000-0002-9408-6647
SPIN-code: 4529-3260

Cand. Sci. (Biology), Senior Research Associate in the Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Irina N. Isakova-Sivak

Institute of Experimental Medicine

Email: isakova.sivak@iemspb.ru
ORCID iD: 0000-0002-2801-1508
SPIN-code: 3469-3600

Dr. Sci. (Biology), Head of the Laboratory of Immunology and Prevention of Viral Infections of the A.A. Smorodintsev Virology Department

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

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Supplementary files

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2. Fig. 1. Results of molecular genetic analysis of H1-Spr: a , separation of amplified fragments in agarose gel; b , amino acid sequence of the bacterial fragment integrated into hemagglutinin

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3. Fig. 2. Replication activity of influenza virus strains in developing chicken embryos at different incubation temperatures. * p < 0.05

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4. Fig. 3. Reproduction of influenza vaccine viruses in the upper and lower respiratory tract of mice ( n = 5 per group). ** p < 0.01. The dotted line indicates the sensitivity threshold of the method

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5. Fig. 4. Results of the immunogenicity study: a , serum IgG to the whole virus A/South Africa/3626/13 (H1N1), enzyme-linked immunosorbent assay ( n = 5 per group) on Day 14 and Day 28 after the first vaccination; b , serum IgG to the recombinant PSP protein on Day 14 after the first vaccination. * р < 0.05 compared with unvaccinated animals (PBS)

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6. Fig. 5. Results of the study of the protective effect of immunization with the recombinant H1-Spr virus: a , changes in the average weight of mice after experimental infection ( n = 10); b , reproduction of the infecting virus A/California/07/09 (H1N1)pdm09-MA in the lungs of mice on Day 3 after experimental infection ( n = 3). PBS, unvaccinated animals

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