Biological role of surface Toxoplasma gondii antigen in development of vaccine

Liu, Keyi; Zhang, Dian-bo; Wei, Quan; Li, Jin; Li, Guiping; Yu, Jie-Tai

doi:10.3748/wjg.v12.i15.2363

Cited by 28 publications

(16 citation statements)

References 17 publications

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“…Furthermore, CLN was proven to trigger apoptosis-like cell death of intracellular parasites (Ni Nyoman and Lüder 2013). Whereas, with NSO, through its strong enhancement of immune cells (T helper 1) counteracts the known strategies employed by Toxoplasma to inhibit T lymphocyte function which in turn leads to T cells unresponsive and exhaustion (Liu et al 2006;Salem et al 2011). Therefore, the effect of NSO +PYR combination on survival rate and tachyzoite counts was comparable to that of CLN+PYR (Rodrigues et al 2014).…”

Section: Discussionmentioning

confidence: 73%

Effect of Nigella sativa oil on experimental toxoplasmosis

2015

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Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii protozoon. It is most commonly treated by pyrimethamine (PYR); however, this was intolerable by many patients. The aim of this study was to assess therapeutic effects of Nigella sativa oil (NSO) alone and combined with pyrimethamine (PYR) compared to a previous combination of clindamycin (CLN) and (PYR). One hundred Albino mice were used in the current study and were equally divided into five groups: normal (I), infected untreated control (II); infected, treated with NSO-only (III); infected, treated with NSO + PYR (IV); and infected, treated with CLN + PYR (V). The virulent RH Toxoplasma strain was used in infection survival rates estimation, impression smears from liver and spleen, and histopathological and ultrastructural studies were done. Liver malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined. Interferon-γ and specific IgM were also measured in sera by ELISA. Results showed that NSO alone has no direct anti-Toxoplasma effect, whereas its combination with PYR produced potent effect that is comparable to CLN + PYR. It significantly increased the survival rate and decreased the parasite density and pathological insult in both liver and spleen. Also, significant increase in interferon-γ level denotes stimulation of cellular immunity. NSO + PYR combination markedly improved the antioxidant capacity of Toxoplasma infected mice compared to the infected untreated ones and to CLN/PYR. In conclusion, although NSO, if administered alone, has significant immunostimulant and antioxidant properties, it failed to decrease tachyzoite counts. Combination of NSO and PYR had synergistic effect in treatment of toxoplasmosis.

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Section: Discussionmentioning

confidence: 73%

Effect of Nigella sativa oil on experimental toxoplasmosis

2015

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“…IFN-γ plays a leading role in restricting both acute phase tachyzoite breeding and chronic phase bradyzoite activation in the cysts. Studies have shown that good DNA vaccines tend to stimulate a Th1-type rather than a Th2-type immune response [8, 33]. The Th2 cytokines IL-4 and IL-10 limit the differentiation of CD4+ T cell to Th1, thereby decreasing the level of IFN-γ [34, 35].…”

Section: Discussionmentioning

confidence: 99%

“…DNA vaccines induce a persistent and strongly protective immune response [6, 7]. For example, T. gondii surface antigen 1 (SAG1) induces effective and durable humoral and cellular immune responses in immunized mice and is regarded as a standard compared to other antigens [8]. …”

Section: Introductionmentioning

confidence: 99%

Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

et al. 2017

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Background Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4.MethodsWe identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain.ResultsMice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls.ConclusionA DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization.

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“…Passive immunization of mice with anti-SAG1 antibody following challenge with a lethal dose of tachyzoites significantly increased survival compared to mice treated with control ascites (7). T. gondii tachyzoites treated with mouse monoclonal antibodies to SAG1 are reported to be gathered together, destroyed, deformed, and swollen, with the formation of holes and gaps on the surface (21).…”

Section: Discussionmentioning

confidence: 99%

Generation of a Neutralizing Human Monoclonal Antibody Fab Fragment to Surface Antigen 1 ofToxoplasma gondiiTachyzoites

Feng

Ohnishi

et al. 2011

Infect Immun

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A combinatorial immunoglobulin gene library was constructed from lymphocytes in peripheral blood of a patient with toxoplasmosis and screened for production of human monoclonal antibody Fab fragments to recombinant surface antigen 1 (SAG1) of Toxoplasma gondii. Two Fab clones, Tox203 and Tox1403, which consisted of a common heavy chain and different light chains, showed positive staining on the entire surface of tachyzoites in confocal microscopy. Sequence analysis of the heavy-chain gene revealed that the closest germ line V segments were VH3-23. The germ line D segment was D1-7, and the closest germ line J segment was JH4. In the light-chain genes, the closest germ line V segment was V1-17 with the J1 or J4 segments. The dissociation constants of these Fab fragments with recombinant SAG1 were 3.09 ؋ 10 ؊9 M for Tox203 and 2.01 ؋ 10 ؊8 M for Tox1403, indicating that the affinity of Tox203 was 7 times higher than that of Tox1403. Preincubation of T. gondii tachyzoites with Tox203 significantly inhibited their attachment to cultured MDBK cells. Passive immunization of mice with Tox203 also significantly reduced mortality after challenge with T. gondii tachyzoites. This is the first report of bacterial expression of human monoclonal antibody Fab fragments to SAG1 of T. gondii. These results also demonstrate that human Fab fragments to SAG1 might be applicable for immunoprophylaxis of toxoplasmosis.Toxoplasma gondii is an obligate intracellular parasite in the phylum Apicomplexa and infects a variety of warm-blooded domestic and wild animals worldwide. It is an important foodborne parasite transmitted primarily from animals to humans through meat, as well as through oocysts shed by cats into the environment (25). Infection in humans is usually asymptomatic in immunocompetent hosts. However, primary infection during pregnancy can result in severe neonatal malformations and ocular complications in the fetus. In immunocompromised hosts such as patients with human immunodeficiency virus/ AIDS, reactivation of the latent infection results in symptomatic diseases such as toxoplasmic encephalitis (14,22). Transmission of T. gondii by organ transplantation from a seropositive donor to a seronegative recipient is also an important potential cause of disease in heart, heart-lung, kidney, liver, and liver-pancreas transplant patients (25).The surface of T. gondii is the first component to contact the host cells. The T. gondii surface is coated by closely related antigens that belong to the surface antigen 1 (SAG1)-related sequences (SRS) superfamily (13, 16). SAG1 is the most abundant and immunogenic of these antigens and is important for the process of invasion. Treatment of T. gondii with mouse monoclonal or rabbit polyclonal antibodies to SAG1 inhibits parasite attachment to host cells (24). Fab fragments derived from a mouse monoclonal antibody also showed dose-dependent inhibition of parasite attachment (23). Therefore, human monoclonal antibodies to SAG1 may be applicable for prevention of transmission and reactivation ...

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Biological role of surface Toxoplasma gondii antigen in development of vaccine

Abstract: SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against T gondii may be regulated by both hormone- and cell-mediated immune response.

Cited by 28 publications

References 17 publications

Effect of Nigella sativa oil on experimental toxoplasmosis

Effect of Nigella sativa oil on experimental toxoplasmosis

Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

Generation of a Neutralizing Human Monoclonal Antibody Fab Fragment to Surface Antigen 1 ofToxoplasma gondiiTachyzoites

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