RHΔgra17Δnpt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

Liang, Qin‐Li; Sun, Li-Xiu; Elsheikha, Hany M.; Cao, Xue-Zhen; Nie, Lan-Bi; Li, Tingting; Li, Tao-Shan; Zhu, Xing‐Quan; Wang, Jin‐Lei

doi:10.3390/microorganisms8030352

Cited by 15 publications

(22 citation statements)

References 31 publications

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“…and multiple stages of parasite infections (Wang et al, 2017(Wang et al, , 2018Xia et al, 2018b;Yang et al, 2019;Liang et al, 2020). In this study, PLK: gra9 vaccination induced a high level of immune response and resisted the infections of tachyzoites from type I or type II strains and cysts from type II strain.…”

Section: Discussionmentioning

confidence: 56%

“…In recent years, active immunization is considered to be the ideal and long-term strategy to induce the host immune response against acute and chronic T. gondii infections ( Loh et al, 2019 ). One means is to develop live attenuated vaccines, a whole parasite-based vaccine, which is the live strain with reduced replication and attenuated virulence but retaining the ability to induce an immune response against a variety of wild-type strain and multiple stages of parasite infections ( Wang et al, 2017 , 2018 ; Xia et al, 2018b ; Yang et al, 2019 ; Liang et al, 2020 ). In this study, PLK :Δ gra9 vaccination induced a high level of immune response and resisted the infections of tachyzoites from type I or type II strains and cysts from type II strain.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies on T. gondii vaccines have been done and reported in animal models. Although compared with nucleic acid vaccines ( Li et al, 2015 ; Zhang et al, 2015 ; Lu et al, 2017 ) and recombinant protein vaccines ( El Bissati et al, 2014 ; Tanaka et al, 2014 ; Wang et al, 2014a , b ), the higher protection against acute or chronic T. gondii infection provided by live attenuated vaccines ( Fox and Bzik, 2015 ; Lagal et al, 2015 ; Abdelbaset et al, 2017 ; Wang et al, 2017 , 2018 ; Xia et al, 2018b ; Yang et al, 2019 ; Liang et al, 2020 ) was highlighted both in short- and long-term vaccination using different strains in the mouse model. However, the safeness of these mutants still needs to be tested in animal models.…”

Section: Introductionmentioning

confidence: 99%

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PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

Galon

Guo

et al. 2021

Front. Microbiol.

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Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa Toxoplasma gondii, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication in vivo, severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Δgra9 in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Δgra9 vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-γ) and interleukin-12 (IL-12), maintained the high T. gondii-specific immunoglobulin G (IgG) level, and mixed high IgG1/IgG2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Δgra9 vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic T. gondii challenges. Together, Δgra9 vaccination provided safe and efficient immune protection against challenging parasites, suggesting that PLK:Δgra9 is a potentially promising live attenuated vaccine candidate.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

Galon

Guo

et al. 2021

Front. Microbiol.

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show abstract

“…Further, partial protection was observed, concerning brain parasite load in the progeny of these animals ( 32 ). Recently, a live-attenuated vaccine of the RH strain was engineered to harbor a deletion of Gra17 and of novel putative transporter 1 ( NPT1 ) gene, encoding a selective arginine transporter ( 33 ). The virulence of this strain (RHΔ gra17 Δ npt1 ) was completely attenuated in vivo .…”

Section: Vaccines In Vertical Infectionmentioning

confidence: 99%

“…The brain cyst burden of immunized dams was significantly lower and no abortions were observed compared with non-immunized infected mice. All pups born from immunized infected mice had about 15 times fewer brain cysts than non-immunized infected mice pups ( 33 ).…”

Section: Vaccines In Vertical Infectionmentioning

confidence: 99%

Vaccines in Congenital Toxoplasmosis: Advances and Perspectives

et al. 2021

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Congenital toxoplasmosis has a high impact on human disease worldwide, inducing serious consequences from fetus to adulthood. Despite this, there are currently no human vaccines available to prevent this infection. Most vaccination studies against Toxoplasma gondii infection used animal models in which the infection was established by exogenous inoculation. Here, we review recent research on potential T. gondii vaccines using animal models in which infection was congenitally established. Endeavors in this field have so far revealed that live or subunit vaccines previously found to confer protection against extrinsically established infections can also protect, at least partially, from vertically transmitted infection. Nevertheless, there is no consensus on the more adequate immune response to protect the host and the fetus in congenital infection. Most of the vaccination studies rely on the assessment of maternal systemic immune responses, quantification of parasitic loads in the fetuses, and survival indexes and/or brain parasitic burden in the neonates. More research must be carried out not only to explore new vaccines but also to further study the nature of the elicited immune protection at the maternal-fetal interface. Particularly, the cellular and molecular effector mechanisms at the maternal-fetal interface induced by immunization remain poorly characterized. Deeper knowledge on the immune response at this specific location will certainly help to refine the vaccine-induced immunity and, consequently, to provide the most effective and safest protection against T. gondii vertical infection.

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Apicomplexan parasites are attenuated by low-energy electron irradiation in an automated microfluidic system and protect against infection with Toxoplasma gondii

Finkensieper,

Mayerle,

Rentería-Solís

et al. 2023

Parasitol Res

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Radiation-attenuated intracellular parasites are promising immunization strategies. The irradiated parasites are able to invade host cells but fail to fully replicate, which allows for the generation of an efficient immune response. Available radiation technologies such as gamma rays require complex shielding constructions and are difficult to be integrated into pharmaceutical production processes. In this study, we evaluated for the first time low-energy electron irradiation (LEEI) as a method to generate replication-deficient Toxoplasma gondii and Cryptosporidium parvum. Similar to other radiation technologies, LEEI mainly damages nucleic acids; however, it is applicable in standard laboratories. By using a novel, continuous, and microfluidic-based LEEI process, tachyzoites of T. gondii and oocysts of C. parvum were irradiated and subsequently analyzed in vitro. The LEEI-treated parasites invaded host cells but were arrested in intracellular replication. Antibody-based analysis of surface proteins revealed no significant structural damage due to LEEI. Similarly, excystation rates of sporozoites from irradiated C. parvum oocysts were similar to those from untreated controls. Upon immunization of mice, LEEI-attenuated T. gondii tachyzoites induced high levels of antibodies and protected the animals from acute infection. These results suggest that LEEI is a useful technology for the generation of attenuated Apicomplexan parasites and has potential for the development of anti-parasitic vaccines.

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RHΔgra17Δnpt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

Cited by 15 publications

References 31 publications

PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

Vaccines in Congenital Toxoplasmosis: Advances and Perspectives

Apicomplexan parasites are attenuated by low-energy electron irradiation in an automated microfluidic system and protect against infection with Toxoplasma gondii

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