Commentary: PLGA nanoparticles as an efficient carrier in Toxoplasma GAP45: a more effective vaccine against acute toxoplasmosis than traditional ones

Nathkapach Kaewpitoon Rattanapitoon^1*Patpicha Arunsan²Nav La³Khristine Sandoval⁴Schawanya Kaewpitoon Rattanapitoon¹

• ¹Parasitic Disease Research, FMC Medical Center of Thailand, Nakhon Ratchasima, Thailand
• ²Faculty of Medicine, Vongchavalitkul University, Nakhon Ratchasima, Thailand, Nakhon Ratchasima, Thailand
• ³Faculty of Pediatric and Medicine, International University, Phnom Penh, Cambodia
• ⁴School of Arts and School, National University, Pasay City, Philippines

convincingly demonstrate that TgGAP45-PLGA nanoparticles not only enhance both humoral and cellular immune responses-including mixed Th1/Th2 and IL-17-driven Th17 profiles-but also significantly reduce parasite burden in target organs (heart and spleen), surpassing oiladjuvanted formulations. This is a particularly notable achievement considering previous attempts with subunit vaccines have struggled to achieve robust CD8⁺ T-cell activation or durable protection (1,2).The mechanistic depth of the study is exemplary. Flow cytometry reveals enhanced dendritic cell maturation (CD83⁺/CD86⁺, MHC-I/II expression), while ELISA and lymphocyte proliferation assays substantiate broad cytokine induction, notably IFN-γ and IL-17. These findings align with the necessity for both antigen-specific cytotoxic responses and mucosal immunity in T. gondii control (3).Compared to earlier efforts using SAG1-based or GRA7-based vaccines (4, 5), TgGAP45 targets the glideosome-a conserved and essential structure for motility and invasion. This strategic antigen selection distinguishes the present study from SAG1-centric vaccines that fail to elicit effective responses against intracellular tachyzoites. Furthermore, PLGA nanoparticles exhibit superior storage stability and safety over liposomes or lipid nanoparticles, which are prone to oxidative degradation (6).Despite its many strengths, the study leaves several compelling avenues for future exploration:1. Chronic Infection Model: While this work focuses on acute toxoplasmosis, the bradyzoite stage is responsible for chronic infection and reactivation. Evaluating vaccine efficacy in models using ME49 or VEG strains would enhance translational relevance (7). 2. Mucosal Immunity and Oral Delivery: Given T. gondii is primarily acquired via the gastrointestinal route, oral or intranasal administration of TgGAP45-PLGA could be transformative. PLGA particles are known to be amenable to mucosal delivery and could be formulated with mucoadhesive polymers to promote Peyer's patch uptake (8). DCs could elucidate transcriptional programs underpinning the observed immune response, enabling biomarker discovery for correlates of protection. 4. Cross-Species Application: Evaluating this platform in target livestock species (e.g., ovine or porcine models) would address the need for agricultural biosecurity and zoonotic transmission control. 5. Antigen Multiplexing: Incorporation of additional antigens-e.g., ROP18, GRA14-in multivalent PLGA formulations may yield synergistic protective effects and reduce escape mechanisms by parasite stage switching. 6. T-Cell Epitope Mapping: Identification of TgGAP45-derived epitopes presented by MHC-I/MHC-II molecules in vaccinated hosts could inform the rational design of synthetic peptide vaccines and MHC tetramer development for immunomonitoring. Zhou et al. have laid a robust foundation for nanotechnology-enabled toxoplasmosis vaccination, and their study stands as a benchmark for rational subunit vaccine engineering. Expanding upon their approach in the directions outlined above could yield a next-generation vaccine that is not only safe and effective but also field-deployable for both human and veterinary applications. Given the zoonotic impact and global prevalence of toxoplasmosis, this line of research is not only scientifically sound but of pressing public health importance.