Abstract
Dengue remains a severe threat to public health. The safety and efficacy of the licensed dengue vaccine is not clinically satisfactory, which necessitate the need of new approach in designing an effective dengue vaccine without eliciting adverse reaction. Herein, we have designed a lipidated multi-epitope peptide vaccine (LipoDV) that can elicit highly targeted humoral and cell-mediated immune responses. To improve its immunogenicity, LipoDV was presented on the surface of MPLA-functionalized polymersome nanoparticles (PNs-LipoDV-MPLA). The as-constructed vaccine delivery platform resembles the structural morphology of DENV owing to its spherical nanoscale particle size and surface immunostimulatory properties given by LipoDV and MPLA that emulating the functional role of DENV E and prM/M proteins respectively. A proof-of-concept study demonstrated that BALB/c mice immunized with PNs-LipoDV-MPLA induced a stronger antigen-specific antibody response with an enhanced cell-mediated immunity as characterized by the elevated IFN-γ secretion in comparison to other tested vaccine candidates which possess a lesser structural trait of DENV. The DENV-mimicking nanoparticles vaccine exhibited negligible toxicity as analyzed by hemolytic test, MTT assay, histopathological examination and abnormal toxicity test on immunized mice. Collectively, our study provides a strong foundation in designing an effective peptide-based vaccine delivery platform against DENV infection.
Highlights
The results demonstrated that the secretion of IFN-γ was significantly elevated in splenocytes from mice vaccinated with PNs-lipidated multi-epitope peptide vaccine (LipoDV)-monophosphoryl-lipid A (MPLA) in comparison to PNs-LipoDV and free LipoDV, while the secretion of IL-2 and IL-4 were comparable among the tested groups (Figure 5)
We have successfully constructed a dengue virus (DENV)-mimicking vaccine delivery platform (PNs-LipoDV-MPLA) based on polymersome nanoparticles intercalated with lipidated antigenic polypeptide targeting B and T cells receptor activation and functionalized with immunostimulatory MPLA on the polymersome surface
Comparative immunization studies in mice showed that the DENV-mimicking vaccine PNs evoked a stronger humoral immune response with an enhanced Th1 activity than its relative vaccine constructs with lesser structural functionality of DENV
Summary
Dengue is an arthropod-borne disease that is transmitted to humans through the bites of female Aedes aegypti or Aedes albopictus mosquitos which have been infected with a dengue virus (DENV). The DENV can be classified into four genetically related but antigenically distinct serotypes, designated as DENV 1–4. Infection by all dengue serotypes causes a wide spectrum of diseases, ranged from asymptomatic/mild febrile illness to severe clinical manifestations that can lead to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [1]. Dengue has been declared to be endemic in Pharmaceutics 2022, 14, 156.
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