Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Abstract

Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

Deletion of Toxoplasma Rhoptry Protein 38 (PruΔrop38) as a Vaccine Candidate for Toxoplasmosis in a Murine Model

“…Toxoplasmosis is a serious zoonotic disease that threatens human and animal health, and vaccination strategies are considered ideal to prevent infection. The objectives are to prevent congenital toxoplasmosis in both women and livestock, prevent/reduce T. gondii tissue cysts in food-producing animals and oocyst shedding in cats [ 8 ]. While various approaches have been attempted to develop and achieve effective anti- T. gondii vaccines with varying degrees of protective immunity, the field of live-attenuated vaccine development has been carried out for safer vaccines for advantages in terms of protective efficacy [ 7 ].…”

“…The development of toxoplasmosis vaccines has evolved from traditional vaccines (e.g., live and inactivated vaccines) to molecular biotechnology vaccines (e.g., recombinant live vector vaccines, recombinant subunit vaccines, and DNA vaccines), but none of these have yet been able to eliminate the formation of cysts effectively. Although live-attenuated vaccines are assumed to induce a stronger immune response against infection and provide more stable protection for experimental animals [ 8 ], only the S48 live-attenuated strain (Toxovax) is a licensed vaccine. S48 is restricted to sheep to reduce abortion and congenital toxoplasmosis, which remains a risk for vulnerable hosts and provides partial protection for sheep [ 9 ].…”

Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

“…Due to the burdensome effects of toxoplasmosis and the failure and/or adverse effects of the currently used therapeutic approaches, several attempts were made to develop vaccines against T. gondii (for a review, see [171]). In 1995, the first commercial vaccine for toxoplasmosis, Ovilis Toxovax, was developed.…”

Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant

“…Although most infections are asymptomatic, the pathogen can cause severe disease manifestations and even death in immunocompromised individuals and significant economic losses to the livestock industry ( Wang et al., 2017 ). T. gondii infection is acquired by consumption of raw or undercooked meat containing tissue cysts and food or water contaminated with oocysts shed from cats ( Mévélec et al., 2020 ). Currently, there are no effective vaccines against toxoplasmosis, and treatment relies on the use of drug therapies.…”