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Toxoplasmosis

The all-encompassing strategy in formulating vaccines and therapeutics s for toxoplasmosis is crucial in mitigating the global burden of the 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 is an infectious disease caused by the parasite Toxoplasma gondii, for warm blooded animals including people, almost every nucleated cell can be invaded by this intracellular protozoan parasite. UN reports have claimed that this parasite has caused an estimated 2 billion chronic infections and the disease has multiple stages with its most common definitive hosts being cats and intermediate hosts being humans and livestock. Transmission of the parasite takes place mostly from the ingestion of oocysts from contaminated food, water, soil, or either by the consumption of undercooked meat that contains 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 formulation of a vaccine against toxoplasmosis is complex given the life cycle of T. gondii which is complicated and T. gondii exists in three different forms, namely tachyzoites, bradyzoites, and sporozoites. A potent vaccine is expected to elicit an immune response against all infracellular stages of the parasite, so that infection and disease do not occur.

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

Available therapy for the management of toxoplasmosis is still limited. The mainstay of therapeutics is the use of chemotherapeutic agents and research is being done on other therapeutic options.

Pyrimethamine and Sulfadiazine: This combination therapeutic works by inhibiting the metabolism of folic acid and it is the first line therapeutic for toxoplasmosis. It is effective, however, it comes with some severe side effects. These include allergic reactions and hematologic toxicity which can stop its use in certain populations such as pregnant women.

Clindamycin and Azithromycin: These are some of the broad-spectrum antibiotics which together with pyrimethamine give better results. As for Clindamycin, he has had some success treating severe forms of the disease, especially in those who cannot take sulfadiazine.

Atovaquone: Although this drug is mainly used in the treatment of pneumocystis pneumonia, atovaquone has proved useful against T. gondii as well. The targeting of the electron transport chain can provide new methods of therapeutic.

There is ongoing research into new classes of compounds which could have an anti Toxoplasma activity. For example, inhibitors of enzymes which have a unique role in metabolism of the parasite such as fatty acid synthesis inhibitors and bumped Kinase inhibitors are under investigation. These compounds may be less toxic and more effective than current therapeutic options.

Our Services

In the course of developing the vaccine, attention is given to detecting and altering the antigens that will trigger the most reliable and expansive immune response against the T. gondii parasite. Such vaccines will, however, have to be developed using reverse vaccinology and structure-based design techniques as our goal is to engineer vaccines that work against multiple life cycle stages of the parasite.

In the context of pharmaceutical research, great attention is given to finding new compounds with high efficacy against T. gondii. We are also refining the pharmacokinetic properties of these compounds in order to increase their bioavailability and decrease their toxicity.

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.