Protection Against Toxoplasma gondii Lethal ME49 Challenge Induced by Influenza Virus-like Particles Containing Dense Granule Protein 14

TL;DR

A vaccine using influenza-based particles with a Toxoplasma protein offers strong and lasting protection against a deadly form of the parasite.

Contribution

Demonstrates GRA14 VLPs as a novel vaccine platform for long-term protection against T. gondii.

Findings

GRA14 VLP vaccination induced strong antibody and T-cell responses in mice.

Vaccinated mice showed reduced brain cysts and 100% survival in short-term tests.

Long-term immunity was sustained with 83% survival and reduced cyst loads.

Abstract

Background/Objectives: Toxoplasma gondii (T. gondii) dense granule antigen 14 (GRA14) is a parasitophorous vacuole membrane protein that plays a critical role in the development of chronic-stage cysts. However, its potential as a vaccine antigen and long-term immunity have not been evaluated using a virus-like particle (VLP) platform. Methods: influenza matrix protein (M1)-based VLPs displaying GRA14 were generated. Female BALB/c mice were intranasally immunized with the VLP vaccine and orally challenged with lethal ME49 cysts either 10 weeks or 32 weeks after prime vaccination for short-term and long-term immunity evaluation, respectively. Results: GRA14 VLP vaccination elicited higher levels of T. gondii-specific IgG, IgG1, and IgG2a antibody responses in sera compared to non-immunized controls. Upon challenge infection, elevated IgG- and IgA-secreting plasma cells, germinal center B cells, and memory B cells were observed, and CD4+, CD8+ T-cells, as well as both Th1 (IFN-γ) and Th2 (IL-4, IL-5) cytokines, were also increased. For the short-term immunity study, vaccinated mice exhibited suppressed cerebral inflammation, significantly reduced brain cyst burdens, maintained stable body weight, and achieved 100% survival. For the long-term study, GRA14 VLPs sustained elevated IgG and IgG1 levels as well as conferred partial yet significant protection, with lower cyst loads and 83% survival. Conclusions: GRA14 VLPs induce durable, balanced humoral and cellular immunity and provide both short-term and long-term protection against lethal chronic toxoplasmosis, supporting their potential as promising vaccine candidates.

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