Protective activity of CR9114 universal antibody isotypes against influenza A virus in vivo

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Abstract

Introduction. Influenza can cause diseases of varying severity, sometimes leading to hospitalization or death. One of the most promising strategies aimed at reducing morbidity and preventing the risks of severe consequences of infection is the use of broad-spectrum antibodies that provide effective protection against infection with seasonal strains.

The aim of the study was to evaluate the protective activity of CR9114 antibodies of the IgG1 and IgA1 isotypes when administered systemically and locally against experimental influenza infection in mice.

Materials and methods. The recombinant antibodies CR9114 of IgG1 or IgA1 isotypes were administered intranasally to BALB/c mice at a dose of 100 or 20 μg 24 hours before infection with influenza virus A/California/07/09 (H1N1)pdm09 virus at a dose of 10 MLD50 (prophylactic regimen) and/or 24 hours after infection (therapeutic regimen). Body weight dynamics were assessed and mortality was recorded in the animals for 14 days after infection.

Results. Intranasal administration of IgG1 or IgA1 isotype antibodies in the therapeutic-prophylactic regimen led to a decrease in viral load in the respiratory tract tissues of infected mice. At the same time, parenteral administration of IgG (but not IgA) also reduced the virus titer in the nasal passages (but not in the lungs) of mice. It was demonstrated that prophylactic administration of IgG1 or IgA1 antibodies provides complete protection against lethal influenza infection.

Conclusion. Intranasal prophylactic administration of human neutralizing antibodies CR9114 of IgG1 or IgA1 isotypes provides 100% survival of mice in lethal infection with influenza A/California/07/09 (H1N1)pdm09 virus. At the same time, Fc fragments of immunoglobulins of different isotypes, responsible for effector functions, appear to influence the degree of antiviral protection.

About the authors

Ekaterina A. Romanovskaya-Romanko

Smorodintsev Research Institute of Influenza

Email: romromka@yandex.ru
ORCID iD: 0000-0001-7560-398X

Cand. Sci. (Biol.), leading researcher, Laboratory of Vector Vaccines

Russian Federation, St. Petersburg

Marina A. Plotnikova

Smorodintsev Research Institute of Influenza

Email: biomalinka@mail.ru
ORCID iD: 0000-0001-8196-3156

Cand. Sci. (Biol.), seniour researcher, Laboratory of Vector Vaccines

Russian Federation, St. Petersburg

Veronika A. Oleynik

Smorodintsev Research Institute of Influenza

Email: working.lyutik@gmail.com
ORCID iD: 0009-0005-3081-0463

laboratory researcher, Laboratory of immunobiological technologies

Russian Federation, St. Petersburg

Aram A. Shaldzhyan

Smorodintsev Research Institute of Influenza

Email: shaldzhyan@yandex.ru
ORCID iD: 0000-0002-8646-6252

laboratory researcher, Laboratory of genetic engineering and recombinant protein expression

Russian Federation, St. Petersburg

Varvara S. Monakhova

Smorodintsev Research Institute of Influenza

Email: varvara.bio@gmail.com
ORCID iD: 0009-0002-9519-5316

Cand. Sci. (Biol.), researcher, Laboratory of immunobiological technologies

Russian Federation, St. Petersburg

Dmitry S. Balabashin

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: dbalabashin@mail.ru
ORCID iD: 0000-0002-7627-0600

Cand. Sci. (Biol.), junior researcher, Laboratory of protein engineering

Russian Federation, Moscow

Viktoriya A. Toporova

Smorodintsev Research Institute of Influenza; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: toporova.viktorija@gmail.com
ORCID iD: 0000-0002-7450-7096

laboratory researcher, Laboratory of immunobiological technologies, Smorodintsev Research Institute of Influenza; researcher, Laboratory of protein engineering, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Russian Federation, St. Petersburg; Moscow

Teymur K. Aliev

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Lomonosov Moscow State University

Email: ta12345@list.ru
ORCID iD: 0000-0002-1753-9614

Cand. Sci. (Chem.), Deputy Head, Competence Center of the National Technological Initiative, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry; researcher, Department of chemical enzymology, Lomonosov Moscow State University

Russian Federation, Moscow; Moscow

Sergey A. Klotchenko

Smorodintsev Research Institute of Influenza

Author for correspondence.
Email: fosfatik@mail.ru
ORCID iD: 0000-0003-0289-6560

Cand. Sci. (Biol.), Head, Laboratory of immunobiological technologies

Russian Federation, St. Petersburg

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Copyright (c) 2025 Romanovskaya-Romanko E.A., Plotnikova M.A., Oleynik V.A., Shaldzhyan A.A., Monakhova V.S., Balabashin D.S., Toporova V.A., Aliev T.K., Klotchenko S.A.

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