Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

Abstract

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

Influence of cationic lipid concentration on properties of lipid–polymer hybrid nanospheres for gene delivery

“…Cell viability was expressed as a percentage based on control (untreated) cells. Additionally, CCK-8 assays were performed with HEK293 cells for groups with different concentrations (15,30,60, and 90 µg).…”

“…DLS analysis revealed that there was a significant size reduction (Figures 2A, S1) compared to bare PLGA NSs (247±12.8 nm), which could be explained by the fact that the processing of those particles in a single step was stabilized by the function of the lipids with PVA. 15,20 It was also found that there was a decrease in particle size Notes: LPHNSs that consisted of DOTAP-protamine-PLGA for efficient gene delivery were fabricated by emulsion-solvent evaporation with a self-assembly process.…”

“…12 Recently, lipid-polymer hybrid nanospheres (LPHNSs) were designed to achieve complementary benefits of liposomes and polymeric NSs. [13][14][15] They were designed to have a biodegradable polymer core and lipid layers. 14,16 Depending on their application, specific fabrication methods have been reported.…”

“…12 Alternatively, a single-step fabrication method was developed, which combined the fabrication process of emulsion-solvent evaporation with the self-assembly of lipids. 15 Although successful outcomes have been achieved using the single-step method, a better understanding of the parameters involved in the fabrication process is required in order to significantly improve the design and fabrication of LPHNSs. 19,20 Specifically, cationic lipids forming outer shells could allow for superior gene-delivery capabilities.…”

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNF&alpha;-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

“…7 PLGA-based vaccine delivery systems possess several advantages such as sustained and controlled antigen release, adjuvant co-encapsulation, protection from degradation by enzymes, as well as the ability of specific tissue targeting. 8,9 Several studies have demonstrated that these nano-sized delivery systems can induce both humoral and cell-mediated specific immune responses via activation of dendritic cells (DCs) in animals in combination with tumor antigenic peptides, 10,11 or parasitic 12 or viral antigenic molecules. 13,14 Several types of micro-or nanoformulations (ie, liposomes, chitosan, PLGA) and antigens have been tested up till now for vaccine development against leishmaniasis with encouraging results.…”