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Volume 13
Issue 11
10.3390/vaccines13111117
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Article

Chimeric Virus-like Particles Formed by the Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465, Simultaneously Displaying the M2e Peptide and the Stalk HA Peptide from Influenza a Virus, Elicit Humoral and T-Cell Immune Responses in Mice

by
Egor A. Vasyagin
1,†,
Anna A. Zykova
1,†,
Elena A. Blokhina
1,
Olga O. Ozhereleva
2,
Liudmila A. Stepanova
2,
Marina A. Shuklina
2,
Sergey A. Klotchenko
2,
Eugenia S. Mardanova
1,* and
Nikolai V. Ravin
1,*
1
Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia
2
Smorodintsev Research Institute of Influenza, Russian Ministry of Health, 197376 St. Petersburg, Russia
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2025, 13(11), 1117; https://doi.org/10.3390/vaccines13111117
Submission received: 17 September 2025 / Revised: 26 October 2025 / Accepted: 28 October 2025 / Published: 30 October 2025
(This article belongs to the Special Issue Bioengineering Strategies for Developing Vaccines)
Versions Notes

Abstract

Background: The extracellular domain of the M2 protein (M2e) and the conserved region of the second subunit of the hemagglutinin (HA2, 76–130 а.а.) of the influenza A virus, could be used to develop broad-spectrum influenza vaccines. However, these antigens have low immunogenicity and require the use of special carriers to enhance it. Virus-like particles (VLPs) formed from viral capsid proteins are among the most effective carriers. Methods: In this work, we obtained and characterized VLPs based on capsid proteins (CPs) of single-stranded RNA bacteriophages Beihai32 and PQ465, simultaneously displaying M2e and HA2 peptides. Results: Fusion proteins expressed in Escherichia coli formed spherical VLPs of about 30 nm in size. Subcutaneous immunization of mice with chimeric VLPs elicited a robust humoral immune response against M2e and the whole influenza A virus, and promoted the formation of cytokine-secreting antigen-specific CD4+ and CD8+ effector memory T cells. Conclusions: VLPs based on CPs of phages Beihai32 and PQ465 carrying conserved peptides M2e and HA2 of the influenza A virus can be used for the development of universal influenza vaccines.
Keywords: virus-like particle; vaccine; ssRNA bacteriophage; M2e peptide; hemagglutinin; influenza A virus; T-cells virus-like particle; vaccine; ssRNA bacteriophage; M2e peptide; hemagglutinin; influenza A virus; T-cells

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MDPI and ACS Style

Vasyagin, E.A.; Zykova, A.A.; Blokhina, E.A.; Ozhereleva, O.O.; Stepanova, L.A.; Shuklina, M.A.; Klotchenko, S.A.; Mardanova, E.S.; Ravin, N.V. Chimeric Virus-like Particles Formed by the Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465, Simultaneously Displaying the M2e Peptide and the Stalk HA Peptide from Influenza a Virus, Elicit Humoral and T-Cell Immune Responses in Mice. Vaccines 2025, 13, 1117. https://doi.org/10.3390/vaccines13111117

AMA Style

Vasyagin EA, Zykova AA, Blokhina EA, Ozhereleva OO, Stepanova LA, Shuklina MA, Klotchenko SA, Mardanova ES, Ravin NV. Chimeric Virus-like Particles Formed by the Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465, Simultaneously Displaying the M2e Peptide and the Stalk HA Peptide from Influenza a Virus, Elicit Humoral and T-Cell Immune Responses in Mice. Vaccines. 2025; 13(11):1117. https://doi.org/10.3390/vaccines13111117

Chicago/Turabian Style

Vasyagin, Egor A., Anna A. Zykova, Elena A. Blokhina, Olga O. Ozhereleva, Liudmila A. Stepanova, Marina A. Shuklina, Sergey A. Klotchenko, Eugenia S. Mardanova, and Nikolai V. Ravin. 2025. "Chimeric Virus-like Particles Formed by the Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465, Simultaneously Displaying the M2e Peptide and the Stalk HA Peptide from Influenza a Virus, Elicit Humoral and T-Cell Immune Responses in Mice" Vaccines 13, no. 11: 1117. https://doi.org/10.3390/vaccines13111117

APA Style

Vasyagin, E. A., Zykova, A. A., Blokhina, E. A., Ozhereleva, O. O., Stepanova, L. A., Shuklina, M. A., Klotchenko, S. A., Mardanova, E. S., & Ravin, N. V. (2025). Chimeric Virus-like Particles Formed by the Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465, Simultaneously Displaying the M2e Peptide and the Stalk HA Peptide from Influenza a Virus, Elicit Humoral and T-Cell Immune Responses in Mice. Vaccines, 13(11), 1117. https://doi.org/10.3390/vaccines13111117

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