Anti-T. gondii chimeric monoclonal antibody, clone B24I2F5

The protozoan parasite Toxoplasma gondii (T. gondii) infects nearly all warm-blooded animals including humans. Generally, infection is acquired through ingestion of or ingestion of contaminated food or drink, or vertical transmission from an infected mother to a child. T gondii infection is usually asymptomatic or mild, and fatal in pregnant women and immune compromised patients. IgM antibodies are potent markers for T gondii infection. IgM antibodies often peak about 1-2 weeks into an infection and then decrease after a few weeks or months. And if it's positive, you're infected because IgM antibodies are volatile. IgM antibody tests, however, are by no means pristine. IgM antibodies can remain in the body months or years after infection, and false positives are common. Immunocompromised patients also lose or block IgM production, making T gondii infection difficult to recognize with IgM antibodies alone. To maximize diagnostic efficiency, IgM antibody testing is typically supplemented with IgG antibody testing, IgG avidity testing and PCR.

The deadliest disease during pregnancy is T. gondii infection: vertical transmission from the mother to the baby. The likelihood of miscarriage, stillbirth, and birth abnormalities decreases with increasing gestational age; however, it affects more at shorter gestational ages. Later infections typically cause worse outcomes, including damage to the central nervous system and sight problems. Preterm pregnancy infections are generally less risky but much more likely to result in severe foetal deformities or miscarriage. As organ systems are still at an early stage of development during embryogenesis, T. gondii infection can permanently disrupt emerging tissues. Mid-gestation infections are relatively rare, as the placenta barrier has evolved and the parasite has less time to clog the entrance and spread into the foetus. Early infections can cause fetal growth restriction, central nervous system defects and congenital toxoplasmosis. More specifically, central nervous system damage can lead to intellectual disabilities, epilepsy and other neurodegenerative disorders. Late pregnancy infections are most likely to cause significant fetal harm, but the chances of severe infection are low. But infants who arrive with no symptoms may show congenital toxoplasmosis symptoms ranging from visual and auditory impairment to intellectual disability in the coming months or years. In immunocompromised patients, acquiring T gondii infection is generally asymptomatic or causes a flu-like feeling of fever, weakness and muscle soreness. After infection, the body generates antibodies that fight the parasite invasion – antibodies known as IgM and IgG. T. gondii acute infections occur when someone eats or drinks infected food or beverages. Once infected, the immune system immediately elicits IgM antibodies to resist the early transmission of parasites. Acute infections tend to go away on their own, and without specific medication, symptoms subside within weeks. Immunocompromised patients are much more vulnerable to infection with T. gondii because their immune systems could fail to kill the organism in the first instance or control the parasite during an ongoing infection, leading to repeated acute toxoplasmosis or severe complications such as pneumonia or encephalitis. After a single infecting infection, T gondii typically progresses into the stage of chronic infection, where it spreads and forms cysts in organs such as the muscles and brain. In healthy individuals, the cysts generally show no symptoms and persist for long periods of time. Yet in immunocompromised individuals, for example with HIV/AIDS or patients who take immunosuppressive medications for organ donation, unresponsive T. gondii cysts could come to life and spawn serious clinical signs such as toxoplasmic encephalitis.

Figure 1. Hypothesis of the Impact of Toxoplasma gondii on Host Cell Genome Integrity (Source: Velásquez, Z.D., et al., 2024)

T. gondii infection has been found in studies to disrupt the host cell cycle and cause DNA damage via a number of effector molecules, affecting the genome stability of the host cell. T. gondii tachyzoites enter host cells early in the infection process and promptly disrupt the host cell cycle, producing S-phase arrest. This arrest is accompanied by DNA double-strand breaks and occurs independently of reactive oxygen species (ROS) generation. It has been discovered that the effector molecules MYR1 and HCE1 play critical roles in this process. Within 15 minutes of infection, host cells show a marked S-phase arrest, and DNA double-strand breaks significantly increase. This phenomenon indicates that T. gondii can impact host cell genome integrity very early in the infection process. MYR1 has been shown to play a crucial role in this DNA damage, as T. gondii lacking MYR1 cannot effectively induce S-phase arrest and DNA damage. In contrast, the absence of HCE1 does not affect these effects, indicating that this process primarily depends on MYR1 rather than the expression of cyclin E1. Other than S-phase arrest and DNA double-strand break, infected cells have other indicators of genomic instability, including binucleation and micronuclei, suggesting cell-wide changes in chromosome segregation. These effects suggest that T gondii infection disrupts host cell mitosis and produces abnormal chromosome distribution, eventually leading to genomic instability. This work has since revealed that T. gondii's DNA damage response (DDR) stimulates the homologous recombination repair system. Yet, this repair process does not fix the DNA damage properly, which results in genomic instability and cell degeneration. In general, T gondii damages host cell DNA with the secreted effector molecules MYR1 and HCE1, and by altering the host cell cycle and the repair of DNA, causes the host cell genome to be annihilated. These alterations not only damage the normal function of host cells, but could also make the environment conducive to T gondii long-term latency and persistence. As a result, detailed investigations of how T. gondii damages DNA will not only provide insight into its infection strategy, but might also uncover new avenues for antiparasitic treatment.

Chimeric Anti-Toxoplasma gondii mAb
T. gondii Monoclonal Antibody, Clone B24I2F5
Anti-Toxoplasma gondii Antibody, B24I2F5 Clone
Monoclonal Antibody Targeting T. gondii