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Volume 24
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10.3390/ijms241411445
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Article

IgGκ Signal Peptide Enhances the Efficacy of an Influenza Vector Vaccine against Respiratory Syncytial Virus Infection in Mice

by
Anastasia Pulkina
,
Kirill Vasilyev
,
Arman Muzhikyan
,
Mariia Sergeeva
,
Ekaterina Romanovskaya-Romanko
,
Anna-Polina Shurygina
,
Marina Shuklina
,
Andrey Vasin
,
Marina Stukova
and
Andrej Egorov
*
Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(14), 11445; https://doi.org/10.3390/ijms241411445
Submission received: 15 June 2023 / Revised: 11 July 2023 / Accepted: 12 July 2023 / Published: 14 July 2023
(This article belongs to the Special Issue Mucosal Delivery of Vaccines)
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Abstract

Intranasal vaccination using influenza vectors is a promising approach to developing vaccines against respiratory pathogens due to the activation of the mucosa-associated immune response. However, there is no clear evidence of a vector design that could be considered preferable. To find the optimal structure of an influenza vector with a modified NS genomic segment, we constructed four vector expressing identical transgene sequences inherited from the F protein of the respiratory syncytial virus (RSV). Two vectors were designed aiming at transgene accumulation in the cytosol. Another two were supplemented with an IgGκ signal peptide prior to the transgene for its extracellular delivery. Surprisingly, adding the IgGκ substantially enhanced the T-cell immune response to the CD8 epitope of the transgene. Moreover, this strategy allowed us to obtain a better protection of mice from the RSV challenge after a single intranasal immunization. Protection was achieved without antibodies, mediated by a balanced T-cell immune response including the formation of the RSV specific effector CD8+ IFNγ+/IL10+-producing cells and the accumulation of Treg cells preventing immunopathology in the lungs of infected mice. In addition to the presented method for optimizing the influenza vector, our results highlight the possibility of achieving protection against RSV through a respiratory-associated T-cell immune response alone.
Keywords: respiratory syncytial virus; vaccine design; influenza vector; regulatory T-cells respiratory syncytial virus; vaccine design; influenza vector; regulatory T-cells

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MDPI and ACS Style

Pulkina, A.; Vasilyev, K.; Muzhikyan, A.; Sergeeva, M.; Romanovskaya-Romanko, E.; Shurygina, A.-P.; Shuklina, M.; Vasin, A.; Stukova, M.; Egorov, A. IgGκ Signal Peptide Enhances the Efficacy of an Influenza Vector Vaccine against Respiratory Syncytial Virus Infection in Mice. Int. J. Mol. Sci. 2023, 24, 11445. https://doi.org/10.3390/ijms241411445

AMA Style

Pulkina A, Vasilyev K, Muzhikyan A, Sergeeva M, Romanovskaya-Romanko E, Shurygina A-P, Shuklina M, Vasin A, Stukova M, Egorov A. IgGκ Signal Peptide Enhances the Efficacy of an Influenza Vector Vaccine against Respiratory Syncytial Virus Infection in Mice. International Journal of Molecular Sciences. 2023; 24(14):11445. https://doi.org/10.3390/ijms241411445

Chicago/Turabian Style

Pulkina, Anastasia, Kirill Vasilyev, Arman Muzhikyan, Mariia Sergeeva, Ekaterina Romanovskaya-Romanko, Anna-Polina Shurygina, Marina Shuklina, Andrey Vasin, Marina Stukova, and Andrej Egorov. 2023. "IgGκ Signal Peptide Enhances the Efficacy of an Influenza Vector Vaccine against Respiratory Syncytial Virus Infection in Mice" International Journal of Molecular Sciences 24, no. 14: 11445. https://doi.org/10.3390/ijms241411445

APA Style

Pulkina, A., Vasilyev, K., Muzhikyan, A., Sergeeva, M., Romanovskaya-Romanko, E., Shurygina, A.-P., Shuklina, M., Vasin, A., Stukova, M., & Egorov, A. (2023). IgGκ Signal Peptide Enhances the Efficacy of an Influenza Vector Vaccine against Respiratory Syncytial Virus Infection in Mice. International Journal of Molecular Sciences, 24(14), 11445. https://doi.org/10.3390/ijms241411445

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