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

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

ACS Pharmacology & Translational Science2025Vol. 8(9), pp. 3182–3198

Arivalagan Ponbharathi, Sivaraj Mehnath, Chithaiyan Kamaladevi Sowndharya, Kannaiyakumar Dharshini, Ammavasi Chandran Ambigaibalan, Murugaraj Jeyaraj

Abstract

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+ and CD8+ T-cell responses, alongside strong IgA and IgG production. Serum bacterial neutralization assay confirms the high amount of antibody production, and it is able to neutralize the bacteria, which was confirmed through confocal and HRTEM analysis. This potent neutralization capability underscores the therapeutic promise of these antibodies for controlling bacterial pathogenesis. Overall, nanovaccine was potentially targeting the antigen-presenting cells (APCs), inherent adjuvant function, and peptides providing systemic immunity.

Abstract

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