Spermine-Functionalized Multiepitope Signaling Peptide Nanovaccine to Stimulate the Systemic Immunity against Pneumonia.

Pneumonia is a high-risk chronic respiratory infection with serious morbidity and mortality rates. Existing vaccines have a poor immune response; vaccine efficiency is limited to the specific serotypes, indicating an urgent need to develop an effective vaccine. The study pursues to design multiepitope signaling peptide nanovaccine using the YSIRK-G/S motif, B/T-cell epitope, and surface modification of the dextran (Dex), functionalized with spermine. It improves the higher load of signaling peptide motif (SPM), pH-responsive delivery, immune cell targeting, endosomal escape, higher antigenicity, and immune activation. The surface modification of dextran enhances nanoparticle uptake, and spermine functionalization regulates particle aggregation. Spermine-modified acetalated dextran nanoparticles (AcDx-Sp NPs) show a higher loading of SPM and uniform spherical morphology with a size range of 105 nm. After impregnation of SPM, the nanovaccine was stable and maintained the structural integrity for 3 days in both PBS and DMEM. In acidic pH conditions, the nanovaccine destabilized to release SPM in 65% in 5 days; at pH 5.0, AcDx was degraded into Dex, providing endosomal escape and releasing the SPM. In vitro studies show the activation of dendritic cells (DCs) and upregulation up to a 200-fold increase in pro-inflammatory cytokine compared to SPM. Comparatively, mice after immunization elicited higher antibody titers and stimulated the robust CD4