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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Respiratory Syncytial Virus Infections* ; Influenza Vaccines* ; Influenza, Human* ; Respiratory Syncytial Virus, Human*/genetics ; Respiratory Syncytial Virus Vaccines*; Animals ; Mice ; Humans ; Antibodies, Viral ; Mice, Inbred BALB C

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.

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0373100122119000065 Federal State Budgetary Institution "Centre for Strategic Planning and Manage-ment of Biomedical Health Risks" of the Ministry of Health of the Russian Fed-eration

Keywords: influenza vector; regulatory T-cells; respiratory syncytial virus; vaccine design

0 (Influenza Vaccines)
0 (Antibodies, Viral)
0 (Respiratory Syncytial Virus Vaccines)

Date Created: 20230729 Date Completed: 20230731 Latest Revision: 20230801

20240829

PMC10380829

10.3390/ijms241411445

37511205