Mic1-3 Knockout<i>Toxoplasma gondii</i>is a good candidate for a vaccine against<i>T. gondii</i>-induced abortion in sheep

Mévélec, Marie-Noëlle; Ducournau, Céline; Ismael, Alaa Bassuny; Olivier, Michel; Sèche, Edouard; Lebrun, Maryse; Bout, Daniel; Dimier‐Poisson, Isabelle

doi:10.1051/vetres/2010021

Cited by 37 publications

(28 citation statements)

References 36 publications

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“…In our study, two peptides derived from this protein, SPA 12–20 and SPA 82–90 , were found to have the ability to stimulate human CD8 + T cells to produce IFN-γ and bound with high affinity all the tested HLA-A02 supertype allele peptides. MIC1-3 knockout T. gondii was considered as a good candidate for a vaccine against T. gondii -induced abortion in sheep [36] and although MIC knockout parasites could be a vaccine, MICs have been found to be immunogenic in mice. Herein, two peptides MIC1 9–17 and MICA2P 11–19 which have high binding affinity for HLA-A02 supertype were identified as CD8 + T cell epitopes that could elicit IFN-γ from T. gondii seropositive HLA-A02 persons.…”

Section: Discussionmentioning

confidence: 99%

Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Cong

Mui

Witola

et al. 2011

Vaccine

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The ideal vaccine to protect against toxoplasmosis in humans would include antigens that elicit a protective T helper cell type 1 immune response, and generate long-lived IFN-γ-producing CD8 + T cells. Herein, we utilized a predictive algorithm to identify candidate HLA-A02 supertype epitopes from T. gondii proteins. Thirteen peptides elicited production of IFN-γ from PBMC of HLA-A02 supertype persons seropositive for T. gondii infection but not from seronegative controls. These peptides displayed high-affinity binding to HLA-A02 proteins. Immunization of HLA-A*0201 transgenic mice with these pooled peptides, with a universal CD4 + epitope peptide called PADRE, formulated with adjuvant GLA-SE, induced CD8 + T cell IFN-γ production and protected against parasite challenge. Peptides identified in this study provide candidates for inclusion in immunosense epitope-based vaccines.

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Section: Discussionmentioning

confidence: 99%

Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Cong

Mui

Witola

et al. 2011

Vaccine

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“…Three out of 34 epitopes elicited responses greater than 50 IFN-γ SFC from seropositive donors PBMC, but not from seronegative donors PBMC ( Figure 6). These peptides and the proteins from which they are derived are: STFWPCLLR (SAG2C [13][14][15][16][17][18][19][20][21] ); SSAYVFSVK (SPA 250-258 ); and AVVSLLRLLK (SPA 89-98 ) adding proteins expressed in sporozoites and bradyzoites to the peptides selected. All peptides identified herein then were found to show high binding affinity to three to five HLA-A03 supertype alleles in the MHC-peptide binding assay ( Table 3).…”

Section: Identification Of New Candidate T Gondii Specific Hla-a*110mentioning

confidence: 99%

“…Attenuated T. gondii tachyzoites (e.g., S48, TS-4, T-203, ΔRPS13)have been employed for live vaccinations of non-human animals [10][11][12][13][14][15]. Parasites attenuated by knockout of gene transcription recently have been proposed as a new type of attenuated vaccine candidate [13][14][15]. However, safety considerations may limit vaccination of humans with live organisms.…”

Section: Introductionmentioning

confidence: 99%

Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8+T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii

Cong¹,

Mui²,

Witola³

et al. 2010

Immunome Res

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BackgroundToxoplasmosis causes loss of life, cognitive and motor function, and sight. A vaccine is greatly needed to prevent this disease. The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype. Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinformatic algorhythms, high measured binding affinity for HLA-A03 supertype molecules, and ability to elicit IFN-γ production by human HLA-A03 supertype peripheral blood CD8+ T cells from seropositive but not seronegative persons.ResultsHerein, when these peptides were administered with the universal CD4+T cell epitope PADRE (AKFVAAWTLKAAA) and formulated as lipopeptides, or administered with GLA-SE either alone, or with Pam2Cys added, we found we successfully created preparations that induced IFN-γ and reduced parasite burden in HLA-A*1101(an HLA-A03 supertype allele) transgenic mice. GLA-SE is a novel emulsified synthetic TLR4 ligand that is known to facilitate development of T Helper 1 cell (TH1) responses. Then, so our peptides would include those expressed in tachyzoites, bradyzoites and sporozoites from both Type I and II parasites, we used our approaches which had identified the initial peptides. We identified additional peptides using bioinformatics, binding affinity assays, and study of responses of HLA-A03 human cells. Lastly, we found that immunization of HLA-A*1101 transgenic mice with all the pooled peptides administered with PADRE, GLA-SE, and Pam2Cys is an effective way to elicit IFN-γ producing CD8+ splenic T cells and protection. Immunizations included the following peptides together: KSFKDILPK (SAG1224-232); AMLTAFFLR (GRA6164-172); RSFKDLLKK (GRA7134-142); STFWPCLLR (SAG2C13-21); SSAYVFSVK(SPA250-258); and AVVSLLRLLK(SPA89-98). This immunization elicited robust protection, measured as reduced parasite burden using a luciferase transfected parasite, luciferin, this novel, HLA transgenic mouse model, and imaging with a Xenogen camera.ConclusionsToxoplasma gondii peptides elicit HLA-A03 restricted, IFN-γ producing, CD8+ T cells in humans and mice. These peptides administered with adjuvants reduce parasite burden in HLA-A*1101 transgenic mice. This work provides a foundation for immunosense based vaccines. It also defines novel adjuvants for newly identified peptides for vaccines to prevent toxoplasmosis in those with HLA-A03 supertype alleles.

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“…Indeed, a live attenuated Toxoplasma tachyzoites S48 vaccine is previously available and it can partially (60%) protect pregnant sheep against toxoplasma infection (Buxton et al, 1991), but now it is difficult to manufacture because it has a short shelf life. Interestingly, we succeeded in development of a potent, successful and effective vaccine against toxoplasmosis that provides highly significant protection against congenital and acquired T. gondii infection in female OF1 mice (more than 96% protection) (Ismael et al, 2006) and in sheep (90% protection) (Mévélec et al, 2010). This vaccine is currently in the approval period and this work was realized in France.…”

Section: Introductionmentioning

confidence: 99%

Development of Improved Preventive and Treatment Strategies for Controlling of Toxoplasmosis in Saudi Arabia

Ismael¹,

Swelum²,

Nassan³

2016

American Journal of Infectious Diseases

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Toxoplasmosis causes severe public health problems and has great veterinary and economic importance worldwide. The present study aims mainly to develop an improved preventive and treatment program for controlling toxoplasmosis in sheep and goats. This study was performed on sheep and goats farm containing 357 animals (300 sheep and 57 goats). This farm had a large numbers of barren ewes, history of abortions (below 4 months), stillbirths, malformations and neonatal losses. Blood samples were collected to determine humeral antibody responses and prevalence of toxoplasmosis. Sections of normal and abnormal tissues were fixed using 10% buffered formalin for histopathological examination. Different and new drug regimens and strategies were used for controlling toxoplasmosis. Sixty-four out of 357 sheep and goats were clinically affected with 17.9% overall morbidity rate. These animals showed certain clinical symptoms of toxoplasmosis, such as abortions and stillbirth. The seroprevalence rate was 15.4%. The titers of ELISA were high before treatment in positive cases while after treatment the titers were decreased for certain level that continued to the end of study. The field treatment revealed that the affected sheep and goats treated with camel lactoferrin (cLf) and chemotherapy combination regimen significantly reduced the overall severity of toxoplasmosis with reduction in IgG titers better than those treated with chemotherapy alone (Pyrimethamine and sulfamethazine) or cLf alone. In conclusion, cLf and chemotherapy combination regimen was success in control of toxoplasmosis in small ruminants.

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Mic1-3 KnockoutToxoplasma gondiiis a good candidate for a vaccine againstT. gondii-induced abortion in sheep

Cited by 37 publications

References 36 publications

Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Development of Improved Preventive and Treatment Strategies for Controlling of Toxoplasmosis in Saudi Arabia

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