Development and evaluation of irradiated vaccine strain against Toxoplasma gondii infection

Background, context, needs: Toxoplasma gondii is an obligate intracellular parasite of birds and mammals causes a serious infectious disease, known as toxoplasmosis, in one-third of global populations (Harun et al., 2020).

Toxoplasmosis is a major food-borne infections with a serious public health concern and socio-economic importance to the animal industry due to abortion, stillbirth and neonatal loss (Yañuk et al., 2017).

The infection in immunocompromised patients results in clinical ocular, neurological, congenital or systematic complications and the severity of the clinical manifestations varies with the virulence of the parasite strain and immune-genetic background of the host (Arruda da Silva Sanfelice et al., 2022).

The establishment of infection by T. gondii requires a series of dynamic interactions between the host and parasite, of which attachment, invasion, replication of the tachyzoites as well as the ability to differentiate to cyst are particularly significant.

The live functional tachyzoites can induce host humoral-mediated immune response to tolerate the establishment and consequences of infection, therefore attenuation of the tachyzoites to with keeping their immunogenicity and hence providing protective immunity is promising (Kannan et al., 2014).

Several studies demonstrated the employing of irradiation in development of potential vaccine for controlling the different infectious diseases of human and animal (Quan et al. 2005).

The ionizing radiation can produce non proliferated, immunologically active and non-pathogenic stages to their hosts with advantage of development of a robust immune responses mimicking to that stimulated by a live and untreated stages (Li et al., 2016). The X-ray have been found to have an effect on the viability of Toxoplasma tachyzoites in vitro (Dubey, 1996).

The research studies suggested that X-rays can be an effective method for reducing the viability of tachyzoites, which could potentially be used as a means of controlling the spread of toxoplasmosis.

However, further research is needed to determine the optimal dose and duration of x-ray exposure, as well as the level of replication of irradiated tachyzoites and immunomodulators production such as cytokine and Reactive Oxygen Species (ROS) from infected cells.

Project hypothesis and aim: In this project, we will test the hypothesis that attenuation of Toxoplasma tachyzoites by irradiation render the tachyzoites unable to replicate inside the host cells while inducing immunogenicity and protective immunity to infections.

We aim to characterize the effect of X-ray irradiation on the parasite infectivity, replication capability and differentiation to the resistant form.

These studies will lay the foundation for the use of irritated infective forms of T. gondii as a vaccine for inducing immune response and protection against the infection.

Research outputs: Production of x-ray-attenuated tachyzoites of T. gondii that have the potential to be used as a vaccine for eliciting humoral and cellular immune response against subsequent infection and providing protection to the host.