Protective Effect of Vaccination with a Combination of Recombinant Surface Antigen 1 and Interleukin-12 against Toxoplasmosis in Mice

Letscher-Bru, Valérie; Villard, Odile; Risse, Bernhard; Zauke, Michael; Klein, Jean‐Paul; Kien, T.

doi:10.1128/.66.9.4503-4506.1998

Cited by 14 publications

(23 citation statements)

References 20 publications

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“…It is also important to remember that, to a certain degree, chimeric antigens represent an artificial product constructed experimentally, which may influence their folding and conformational stability and in turn impact immunogenicity and immune polarization [31]. These results emphasize the importance of each antigenic component used and its length on the overall activity of the resulting fusion proteins, even if each antigen is individually highly immunogenic, such as the SAG1, MIC1 and MAG1 antigens [29,30,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

et al. 2019

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Toxoplasmosis may pose a serious threat for individuals with weakened or undeveloped immune systems. However, to date, there is no specific immunoprophylaxis for humans. Thus, the aim of this study was to evaluate the immunogenicity of three trivalent—SAG2-GRA1-ROP1L (SGR), SAG1L-MIC1-MAG1 (SMM), and GRA1-GRA2-GRA6 (GGG)—and two tetravalent—SAG2-GRA1-ROP1-GRA2 (SGRG) and SAG1-MIC1-MAG1-GRA2 (SMMG)—chimeric T. gondii proteins, as well as their protective potential against chronic toxoplasmosis in laboratory mice. All three trivalent recombinant proteins possessed immunogenic properties, as defined by specific humoral and cellular responses in vaccinated mice characterized by the synthesis of specific IgG (IgG1/IgG2a) antibodies in vivo and the release of Th1/Th2 cytokines by stimulated splenocytes in vitro. Immunization with all three recombinant proteins provided partial protection against toxoplasmosis, although the protective capacity strongly depended on the individual antigenic composition of each preparation. The antigens providing the highest (86%) and lowest (45%) protection, SGR and SMM, respectively, were supplemented with GRA2 antigen fragment, to form the tetravalent chimeric proteins SGRG and SMMG. Further study revealed that the tetravalent preparations exhibited high immunogenic potential; however, the addition of another antigen to the recombinant protein structure had distinct effects on the protection generated, compared to that of the trivalent counterparts, depending on the antigen tested.

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Section: Discussionmentioning

confidence: 99%

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

et al. 2019

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“…Among these, SAG1 and SAG2 proteins are mainly involved in host cell invasion which are accountable for inducing immune response against Toxoplasma [16,17]. Highly conserved in T. gondii RH strain, SAG1 (30 kDa protein) based recombinant vaccine has been extensively investigated and could potentially protect against cyst formation in brain and acute phase toxoplasomsis [18][19][20]. A study has found significant reduction of fetus infection by immunizing BALB/c mice with SAG1 recombinant protein in congenital toxoplasmosis.…”

Section: Introductionmentioning

confidence: 99%

Induction of Th1 type-oriented humoral response through intranasal immunization of mice with SAG1-Toxoplasma gondiipolymeric nanospheres

Naeem

Sana

Islam

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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About one-third of the world population is prone to have infection with T. gondii, which can cause toxoplasmosis in the developing fetus and in people whose immune system is compromised through disease or chemotherapy. Surface antigen-1 (SAG1) is the candidate of vaccine against toxoplasmosis. Recent advances in biotechnology and nano-pharmaceuticals have made possible to formulate nanospheres of recombinant protein, which are suitable for sub-unit vaccine delivery. In current study, the local strain was obtained from cat feces as toxoplasma oocysts. Amplified 957 bp of SAG1 was cloned into pGEM-T and further sub-cloned into pET28-SAG1. BL21 bacteria were induced at different concentrations of isopropyl β-d-1-thiogalactopyranoside for the expression of rSAG1 protein. An immunoblot was developed for the confirmation of recombinant protein expression at 35 kDa that was actually recognized by anti-HIS antibodies and sera were collected from infected mice. PLGA encapsulated nanospheres of recombinant SAG1 were characterized through scanning electron microscopy. Experimental mice were intraperitoneally immunized with rSAG1 protein and intra-nasally immunized with nanosphere. The immune response was evaluated by indirect ELISA. In results intra-nasally administered rSAG1 in nanospheres appeared to elicit elevated responses of specific IgA and IgG2a than in control. Nanospheres of rSAG1 are found to be a bio-compatible candidate for the development of vaccine against T. gondii.

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“…Therefore, most of the more recent protocols have focused on development of recombinant vaccines. As target antigens, there is great interest in tachyzoite surface proteins, particularly surface antigen-1 (SAG1) (Letscher-Bru et al, 1998;Petersen et al, 1998;Nielsen et al, 1999;Angus et al, 2000;Haumont et al, 2000;Bonenfant et al, 2001;Couper et al, 2003). In addition, a few studies have also been performed with SAG2 and SAG3 (Mishima et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Vaccination with Replication-Deficient Recombinant Adenoviruses Encoding the Main Surface Antigens ofToxoplasma gondiiInduces Immune Response and Protection Against Infection in Mice

et al. 2006

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We have generated recombinant adenoviruses encoding three genetically modified surface antigens (SAGs) of the parasite Toxoplasma gondii, that is, AdSAG1, AdSAG2, and AdSAG3. Modifications included the removal of their glycosylphosphatidylinositol (GPI) anchoring motifs and, in some cases, the exchange of the native signal peptide for influenza virus hemagglutinin signal sequence. Adenovirus immunization of BALB/c mice elicited potent antibody responses against each protein, displaying a significant bias toward a helper T cell type 1 (Th1) profile in animals vaccinated with AdSAG1. Furthermore, the presence of parasite-specific IFN-gamma-producing T cells was analyzed by proliferation assays and enzyme-linked immunospot assays in the same animals. Splenocytes from immunized mice secreted IFN-gamma after in vitro stimulation with tachyzoite lysate antigen or with a fraction enriched for membrane-purified GPI-anchored proteins (F3) from the T. gondii tachyzoite surface. Epitopes recognized by CD8+ T cells were identified in SAG1 and SAG3, but not SAG2, sequences, although this protein also induced a specific response. We also tested the capacity of the immune responses detected to protect mice against a challenge with live T. gondii parasites. Although no protection was observed against tachyzoites of the highly virulent RH strain, a significant reduction in cyst loads in the brain was observed in animals challenged with the P-Br strain. Thus, up to 80% of the cysts were eliminated from animals vaccinated with a mixture of the three recombinant viruses. Because adenoviruses seemed capable of inducing Th1-biased protective immune responses against T. gondii antigens, other parasite antigens should be tested alone or in combination with those described here to further develop a protective vaccine against toxoplasmosis.

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Protective Effect of Vaccination with a Combination of Recombinant Surface Antigen 1 and Interleukin-12 against Toxoplasmosis in Mice

Cited by 14 publications

References 20 publications

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

Induction of Th1 type-oriented humoral response through intranasal immunization of mice with SAG1-Toxoplasma gondiipolymeric nanospheres

Vaccination with Replication-Deficient Recombinant Adenoviruses Encoding the Main Surface Antigens ofToxoplasma gondiiInduces Immune Response and Protection Against Infection in Mice

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