Recent Advances in Toxoplasma gondii Immunotherapeutics

Lim, Sherene Swee-Yin; Othman, Rofina Yasmin

doi:10.3347/kjp.2014.52.6.581

Cited by 41 publications

(37 citation statements)

References 89 publications

(84 reference statements)

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“…Current research on developing a human or animal Toxoplasma vaccine has been an ongoing but incredibly challenging effort (104). Recent advances in immunotherapeutics designed to boost the host response to the parasite or to parasite antigens may aid effective multispecies vaccine development, ideally resulting in disease prevention or reduction and interruption of transmission (105). Immunomodulators in combination with anti-Toxoplasma compounds are another area of future promise (106).…”

Section: Resultsmentioning

confidence: 99%

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

Neville

Zach

Wang

et al. 2015

Antimicrob Agents Chemother

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e Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts.

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Section: Resultsmentioning

confidence: 99%

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

Neville

Zach

Wang

et al. 2015

Antimicrob Agents Chemother

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“…T. gondii causes toxoplasmosis in humans and many domestic and wildlife animals, with great economic impact especially in sheep but also in many other animal species (1). Human toxoplasmosis causes serious pathology in immune-suppressed individuals.…”

mentioning

confidence: 99%

In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum

Winzer

Müller

Aguado‐Martínez

et al. 2015

Antimicrob Agents Chemother

124

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eWe report on the in vitro effects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulent Neospora caninum isolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains of Toxoplasma gondii (RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC 50 s) ranging from 20 nM (T. gondii RH) to 360 nM (N. caninum Nc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treated N. caninum beta-galactosidase-expressing parasites. However, such complexes were not seen in a transgenic T. gondii strain that expressed CDPK1 harboring a mutation (G to M) in the gatekeeper residue. In T. gondii ME49 and N. caninum NcLiv, exposure of cultures to BKI-1294 resulted in the elevated expression of mRNA coding for the bradyzoite marker BAG1. Unlike in bradyzoites, SAG1 expression was not repressed. Immunofluorescence also showed that these multinucleated complexes expressed SAG1 and BAG1 and the monoclonal antibody CC2, which binds to a yet unidentified bradyzoite antigen, also exhibited increased labeling. In a pregnant mouse model, BKI-1294 efficiently inhibited vertical transmission in BALB/c mice experimentally infected with one of the two virulent isolates Nc-Liv or Nc-Spain7, demonstrating proof of concept that this compound protected offspring from vertical transmission and disease. The observed deregulated antigen expression effect may enhance the immune response during BKI-1294 therapy and will be the subject of future studies. N eospora caninum is a cyst-forming apicomplexan parasite that is closely related to Toxoplasma gondii but exhibits distinct differences in transmission patterns, virulence, host specificity, immunogenetic aspects, and the pathology it induces. T. gondii causes toxoplasmosis in humans and many domestic and wildlife animals, with great economic impact especially in sheep but also in many other animal species (1). Human toxoplasmosis causes serious pathology in immune-suppressed individuals. In addition, if a seronegative mother acquires primary infection during pregnancy, human toxoplasmosis can lead to abortion, microcephalus and hydrocephalus, and other fetal abnormalities causing intellectual disability (2). N. caninum is a veterinary health problem and represents one of the most important infectious causes of bovine abortion, stillbirth, and the birth of weak calves, with an economic impact of over $1.3 billion (3-5). In addition, N. caninum causes neuromuscular disease in dogs, and neosporosis has also been detected in a wide range of other species of livestock and wild animals worldwide.Despite their differences, an important common feature of these parasites is their ability to invade and replicate within a wide range of cell types and tissues, where they reside in an intracellular parasitophorous vacuole, surrounded by a parasitophorous vacuole me...

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“…It has been known that treatment when administered as soon as seroconversion is detected significantly minimizes the severity of fetal lesions after transmission has occurred [11,16]. The recently commercialized LDBIO Toxo II IgG® test has been shown to be very reliable in the confirmation of low titers of IgG or titers close to the cut-off of the routine quantitative techniques [12].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Immunoblot for Early Detection of Seroconversion in Pregnant Women

Yaacoub¹

2015

J Bacteriol Parasitol

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The recently commercialized LDBIO Toxo II IgG ® immunoblot test has been shown to be very reliable in the early detection of toxoplasmic seroconversion in pregnant woman. A positive result is defined by the presence of at least three among the five following bands: 30, 31, 33, 40 and 45 kDa, the 30 kDa band being required as a positivity criteria. Moreover, it has been reported that the detection of the sole 30 kDa band was sufficient for this purpose.We report herein the result of serologic follow-up of three initially seronegative pregnant woman by using ELISAIgG, IFAT-IgG, ELISA-IgM and LDBIO Toxo II IgG ® . In two of them, seroconversion was highly suspected on the detection of 30 kDa band and positivity of IgM test and further confirmed by the positivity of conventional tests for IgG. In contrast, in the third case, despite the appearance of the 30 kDa band during the follow-up, seroconversion was discarded as ELISA-IgG and IFAT-IgG tests remained negative and only one additional band was later detected on LDBIO Toxo II IgG ® .Our findings suggest that the detection of the 30 kDa band together with the positivity of IgM test can be considered as a seroconversion criteria but confirmation by further positivity of conventional tests is recommended.

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Recent Advances in Toxoplasma gondii Immunotherapeutics

Cited by 41 publications

References 89 publications

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum

Assessment of Immunoblot for Early Detection of Seroconversion in Pregnant Women

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