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

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