Searching for a vaccine against toxoplasmosis

Around 1/3 of the world"s population is infected by Toxoplasma gondii, an obligatory intracellular parasite that causes toxoplasmosis (1). This infection can lead to encephalitis and death of immunocompromised individuals. In pregnant women, primo infection or re-infection with highly virulent strains can lead to abortion or congenital toxoplasmosis (1). To date, there is no effective human vaccine, and recent studies using nanotechnology in vaccine development showed promising results (2).

The goal of this work was to optimize a poly lactic-co-glycolic acid (PLGA) delivery nano system containing an antigen extract of T. gondii for intranasal administration inducing an effective immune response and protection against infection. Single emulsion method was used for the synthesis of the formulation and its physical chemical parameters were evaluated by nanoparticle tracking analysis and dynamic light scattering. Lowry assay and UV-Vis spectroscopy were used to determine the encapsulation efficiency. To access biocompatibility of the nanoformulation, cell viability assay was performed. To infer about the permeation of the nasal epithelium and delivery to target cells, cell permeability and cell internalization assays were performed using human nasal epithelial cells (RPMI) and mouse bone marrow-derived dendritic cells (BMDCs), respectively.

The nanoparticles obtained presented a size of 207 nm, a polydispersity index of 0.227, a zeta potential of -14.15 mV, which are adequate physical-chemical properties for induction of immune response, and an encapsulation efficiency of 55%. After 24h of exposure there was no cytotoxicity for a nanoparticle concentration of 7.5 mg/ml in L929 and RPMI cell lines, and 0.25 mg/ml in BMDCs. At the same timepoint, nanoparticles reached a 66.4% of permeability across a nasal epithelial monolayer. There was also a time-dependent increase in the nanoparticle uptake by BMDCs.

These data are determinant to advance in the development of an effective vaccine preventing congenital toxoplasmosis.

References

Borges M, Magalhães Silva T, Brito C, Teixeira N, Roberts CW. How does toxoplasmosis affect the maternal-foetal immune interface and pregnancy? Parasite Immunol. 2019;41(3):e12606. Brito C, Lourenço C, Magalhães J, Reis S, Borges M. Nanoparticles as a Delivery System of Antigens for the Development of an Effective Vaccine against Toxoplasma gondii. Vaccines (Basel). 2023;11(4).