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Toxoplasmosis

The comprehensive strategy in creating vaccines and therapeutics s for toxoplasmosis plays a pivotal role in combatting the worldwide impact of this condition. Through the utilization of cutting-edge scientific exploration and inventive technologies, our company remains steadfast in progressing the battle against this prevalent parasitic ailment.

Overview of Toxoplasmosis

Toxoplasmosis, a zoonotic ailment caused by the intracellular protozoan parasite Toxoplasma gondii, has the ability to invade nearly any nucleated cell in warm-blooded creatures, including humans. It is estimated that approximately 2 billion individuals worldwide are chronically infected by this parasite. The disease entails a sophisticated life cycle involving definitive hosts, such as felines, and intermediate hosts like humans and livestock. Transmission primarily occurs through the ingestion of oocysts from contaminated food, water, or soil, or by consuming undercooked meat containing tissue cysts.

Summary of some of the targets for chemotherepeutic interventions against Toxoplasma gondii.Fig.1 Summary of some of the targets for Toxoplasma gondii. (Smith N. C., et al., 2021)

Vaccine Development for Toxoplasmosis

The development of a vaccine against toxoplasmosis has been a significant challenge due to the complex life cycle of T. gondii and its ability to exist in three distinct forms: tachyzoites, bradyzoites, and sporozoites. An effective vaccine must induce a robust immune response targeting all stages of the parasite to prevent infection and disease.

Table 1. Examples of experimental murine vaccines against Toxoplasma gondii. (Smith N. C., et al., 2021)

Live Attenuated Vaccines
Gene deleted Toxoplasma Immunising Strain Toxoplasma Challenge Strain Murine Host Strain Immune Response Vaccine Trial Results Summary
CDPK2 PruΔcdpk2 RH, PRU Kunming IgG, Th1/Th2 cytokines Protection of host against lethal challenge; partial reduction of brain cyst numbers.
Gra17 and NPT1 RHΔgra17Δnpt1 RH, PRU Kunming IgG, IFN-γ, IL-2, IL-10 and IL-12 Protection of host against lethal challenge; partial reduction of brain cyst numbers; partial protection against congenital toxoplasmosis
Tyrosine kinase-like 1 RHΔtkl1 RH, PRU Kunming IgG1, IgG2a, IFN-γ, IL-2 Protection of host against lethal challenge; partial reduction of brain cyst numbers; partial protection against congenital toxoplasmosis
Subunit/Recombinant Vaccines
Antigen Formulation/Adjuvant Toxoplasma Challenge Strain Murine Host Strain Immune Response Vaccine Trial Results Summary
Recombinant GRA2 Monophosphorryl lipid A (MPL) Tehran C57BL/6 IgG, IFN-γ Partial reduction of brain cyst numbers
Recombinant calcium-dependent protein kinases family, TgCDPK1 BALB/c RH BALB/c IgG, IFN-γ, IL-12, IL-10 Prolonged survival of host
DNA Vaccines
Gene Formulation/Adjuvant Toxoplasma Challenge Strain Murine Host Strain Immune Response Vaccine Trial Results Summary
GRA7 and ROP2 - RH BALB/c IgG2a, IFN-y Prolonged survival of host
T. gondii profilin (TgPF) IL-15 PRU Kunming IgG, IgG2a, IFN-γ, IL-2, IL-4, IL-10 Partial reduction of brain cyst numbers
ROP22  - RH BALB/c IgG1, IgG2a, IL-2, IFN-γ Prolonged survival of host; partial reduction of brain cyst numbers

Therapeutics Development for Toxoplasmosis

Therapeutic options for managing toxoplasmosis are currently limited. The mainstay of therapeutics involves the use of chemotherapeutic agents, though research continues to explore novel therapeutic avenues.

Pyrimethamine and Sulfadiazine: This combination therapy targets folic acid metabolism and is considered the first-line therapeutics for toxoplasmosis. While effective, it is associated with significant side effects, including hematologic toxicity and allergic reactions, which can limit its use, particularly in vulnerable populations such as pregnant women.

Clindamycin and Azithromycin: These antibiotics are often combined with pyrimethamine to enhance therapeutic outcomes. Clindamycin, in particular, has been shown to be effective in treating severe cases of toxoplasmosis, especially in patients who cannot tolerate sulfadiazine.

Atovaquone: Primarily used for the therapeutics of pneumocystis pneumonia, atovaquone has also demonstrated efficacy against T. gondii. Its unique mechanism of action, which targets the electron transport chain, presents an alternative therapeutics pathway.

Research is actively exploring new classes of compounds with anti-Toxoplasma activity. For instance, inhibitors targeting the parasite's unique metabolic pathways, such as fatty acid synthesis inhibitors and bumped kinase inhibitors, are under investigation. These compounds offer the potential for reduced toxicity and improved efficacy compared to existing therapies.

Our Services

In our pursuit of vaccine development, we concentrate on pinpointing and modifying antigens capable of eliciting a comprehensive and potent immune reaction against T. gondii. By employing reverse vaccinology and structure-based design methodologies, our objective is to fashion vaccines that combat various life cycle phases of the parasite.

Within the domain of drug discovery, our focus is on unearthing innovative compounds that exhibit strong efficacy against T. gondii. We dedicate our efforts to refining the pharmacological characteristics of these compounds to enhance bioavailability and diminish toxicity levels.

We are also actively exploring the potential of immunotherapies and nanotechnology in the context of toxoplasmosis therapeutics. This includes the development of monoclonal antibodies with specificity for key parasite antigens and the design of nanoparticles for targeted drug delivery. If you are interested in our services, please feel free to contact us.

References

  1. Smith, Nicholas C., et al. "Control of human toxoplasmosis." International journal for parasitology 51.2-3 (2021): 95-121.
  2. Alday, P. Holland, and Joseph Stone Doggett. "Drugs in development for toxoplasmosis: advances, challenges, and current status." Drug design, development and therapy (2017): 273-293.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.