Intranasal immunisation of the recombinant Toxoplasma gondii receptor for activated C kinase 1 partly protects mice against T. gondii infection

Wang, Hailong; Pang, Min; Yin, Lei; Zhang, Jianhong; Meng, Xiangjun; Yu, Bin; Guo, Rui; Bai, Ji‐Zhong; Zheng, Guoping; Yin, Guangwen

doi:10.1016/j.actatropica.2014.05.001

Cited by 12 publications

(7 citation statements)

References 55 publications

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“…In recent years, vaccination with several protein antigen combinations resulted in increased survival rates in mice following lethal challenge with type I parasite. The most significant gains in survival rates were reported for vaccine antigen SAG1 (80%) [ 17 ], SAG1+SAG2 (83%) [ 18 ], TgACT (50%) [ 19 ], and TgRACK-1 (45%) [ 20 ]. Among these findings, the unique study by Chuang et al [ 17 ] used poly (lactide-co-glycolide) (PLG) microparticle encapsulation of the SAG1 and SAG2 protein antigens as a sustained-release vaccine formulation, which is an attractive concept for inducing prolonged disease immunity.…”

Section: Protein Vaccinesmentioning

confidence: 99%

Recent Advances in Toxoplasma gondii Immunotherapeutics

Lim

Othman

2014

Korean J Parasitol

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Toxoplasmosis is an opportunistic infection caused by the protozoan parasite Toxoplasma gondii. T. gondii is widespread globally and causes severe diseases in individuals with impaired immune defences as well as congenitally infected infants. The high prevalence rate in some parts of the world such as South America and Africa, coupled with the current drug treatments that trigger hypersensitivity reactions, makes the development of immunotherapeutics intervention a highly important research priority. Immunotherapeutics strategies could either be a vaccine which would confer a pre-emptive immunity to infection, or passive immunization in cases of disease recrudescence or recurrent clinical diseases. As the severity of clinical manifestations is often greater in developing nations, the development of well-tolerated and safe immunotherapeutics becomes not only a scientific pursuit, but a humanitarian enterprise. In the last few years, much progress has been made in vaccine research with new antigens, novel adjuvants, and innovative vaccine delivery such as nanoparticles and antigen encapsulations. A literature search over the past 5 years showed that most experimental studies were focused on DNA vaccination at 52%, followed by protein vaccination which formed 36% of the studies, live attenuated vaccinations at 9%, and heterologous vaccination at 3%; while there were few on passive immunization. Recent progress in studies on vaccination, passive immunization, as well as insights gained from these immunotherapeutics is highlighted in this review.

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Section: Protein Vaccinesmentioning

confidence: 99%

Recent Advances in Toxoplasma gondii Immunotherapeutics

Lim

Othman

2014

Korean J Parasitol

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“…Therefore, preventing infection at these sites via mucosal active vaccines is a promising and rational approach for vaccine development. Intranasal immunization is an effective and safe way of providing a disseminated mucosal immunity as well as systemic immunity [ 23 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B-cell epitopes via an intranasal route against toxoplasmosis in mice

Zhang

Yin

et al. 2015

Parasites Vectors

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BackgroundToxoplasma gondii is a ubiquitous protozoan intracellular parasite, the causative agent of toxoplasmosis, and a worldwide zoonosis. Apical membrane antigen-1 (AMA1) and rhoptry neck protein (RON2, RON4) are involved in the invasion of T. gondii.MethodsThis study chemically synthesized peptides of TgAMA1, TgRON2 and TgRON4 that contained the T- and B-cell epitopes predicted by bioinformatics analysis. We evaluated the systemic response by proliferation, cytokine and antibody measurements as well as the mucosal response by examining the levels of antigen-specific secretory IgA (SIgA) in the nasal, vesical and intestinal washes obtained from mice after nasal immunization with single (AMA1, RON2, RON4) or mixtures of peptides (A1 + R2, A1 + R4, R2 + R4, A1 + R2 + R4). We also assessed the parasite burdens in the liver and brain as well as the survival of mice challenged with a virulent strain.ResultsThe results showed that the mice immunized with single or mixed peptides produced effective mucosal and systemic immune responses with a high level of specific antibody responses, a strong lymphoproliferative response and significant levels of gamma interferon (IFN-γ), interleukin-2 (IL-2) and IL-4 production. These mice also elicited partial protection against acute and chronic T. gondii infection. Moreover, our study indicated that mixtures of peptides, especially the A1 + R2 mixture, were more powerful and efficient than any other single peptides.ConclusionsThese results demonstrated that intranasal immunisation with peptides of AMA1, RON2 and RON4 containing T- and B-cell epitopes can partly protect mice against toxoplasmosis, and a combination of peptides as a mucosal vaccine strategy is essential for future Toxoplasma vaccine development.

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“…On the 30th day after being challenged, the infected mice were anaesthetised with sodium pentobarbital, and the numbers of tachyzoites in the livers and brains were measured using realtime PCR assays as previously described [38,39,41,44]. For survival analysis, the acute infected mice were monitored thrice daily until 30 days after the tachyzoite challenge.…”

Section: Challenge Infectionmentioning

confidence: 99%

“…Furthermore, the non-invasive and acceptable route of intranasal vaccination is becoming more attractive because it requires lower doses of antigens, while it triggers mucosal immune responses at local and distant mucosa sites, as well as systemic and cellular immune response [27]. Therefore, several recombinant T. gondii proteins prepared by other groups such as rhoptry protein 2 (ROP2) [13], ROP18 [31], malate dehydrogenase (MDH) [19], actin depolymerizing factor (ADF) [18], as well as ours such as actin [44], phosphoglycerate mutase 2 (PGAM 2) [41], ROP17 [42], receptor for activated C kinase 1 (RACK1) [39] and protein disulfide isomerase (PDI) [38] have been tested to assess their immunoprotective effects produced by intranasal immunisation. Although the abovementioned recombinant proteins were capable of triggering both cellular and humoral responses, they all conferred partial protective efficacy against toxoplasmosis.…”

Section: Introductionmentioning

confidence: 99%

Intranasal immunisation with recombinant Toxoplasma gondii uridine phosphorylase confers resistance against acute toxoplasmosis in mice

Yin,

Ren,

You

et al. 2023

Parasite

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Toxoplasmosis is caused by Toxoplasma gondii, which infects all warm-blooded animals, including humans. Currently, control measures for T. gondii infection are insufficient due to the lack of effective medications or vaccines. In this paper, recombinant T. gondii uridine phosphorylase (rTgUPase) was expressed in Escherichia coli and purified via Ni2+-NTA agarose. rTgUPase was inoculated intranasally into BALB/c mice, and the induced immune responses were evaluated by mucosal and humoral antibody and cytokine assays and lymphoproliferative measurements. Moreover, the protective effect against the T. gondii RH strain infection was assessed by calculating the burdens of tachyzoites in the liver and brain and by recording the survival rate and time. Our results revealed that mice immunised with 30 μg rTgUPase produced significantly higher levels of secretory IgA (sIgA) in nasal, intestinal, vaginal and vesical washes and synthesised higher levels of total IgG, IgG1 and, in particular, IgG2a in their blood sera. rTgUPase immunisation increased the production of IFN-gamma, interleukin IL-2 and IL-4, but not IL-10 from isolated mouse spleen cells and enhanced splenocyte proliferation in vitro. rTgUPase-inoculated mice were effectively protected against infection with the T. gondii RH strain, showing considerable reduction of tachyzoite burdens in liver and brain tissues after 30 days of infection, and a 44.29% increase in survival rate during an acute challenge. The above findings show that intranasal inoculation with rTgUPase provoked mucosal, humoral and cellular immune responses and indicate that rTgUPase might serve as a promising vaccine candidate for protecting against toxoplasmosis.

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Intranasal immunisation of the recombinant Toxoplasma gondii receptor for activated C kinase 1 partly protects mice against T. gondii infection

Cited by 12 publications

References 55 publications

Recent Advances in Toxoplasma gondii Immunotherapeutics

Recent Advances in Toxoplasma gondii Immunotherapeutics

Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B-cell epitopes via an intranasal route against toxoplasmosis in mice

Intranasal immunisation with recombinant Toxoplasma gondii uridine phosphorylase confers resistance against acute toxoplasmosis in mice

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