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Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of Toxoplasma gondii as a Potential Vaccine Candidate for Toxoplasmosis.

ABSTRACT: This study was carried out to evaluate the vaccination effect of a virus-like particle (VLP) including the surface antigen 1 (SAG1) of Toxoplasma gondii as a potential vaccine for toxoplasmosis. The SAG1 virus-like particles (SAG1-VLPs) were expressed by Sf9 cells, and their expression was confirmed through cloning, RT-PCR analysis, and western blot method. The immunogenicity and vaccine efficacy of SAG1-VLPs were assessed by the antibody response, cytokine analysis, neutralization activity, splenocyte assay, and survival rates through a mouse model. In particular, IgG, IgG1, IgG2a, and IgA were markedly increased after immunization, and the survival rates of T. gondii were strongly inhibited by the immunized sera. Furthermore, the immunization of SAG1-VLPs effectively decreased the production of specific cytokines, such as IL-1?, IL-6, TNF-?, and IFN-?, after parasite infection. In particular, the immunized group showed strong activity and viability compared with the non-immunized infection group, and their survival rate was 75%. These results demonstrate that SAG1-VLP not only has the immunogenicity to block T. gondii infection by effectively inducing the generation of specific antibodies against T. gondii, but is also an effective antigen delivery system for preventing toxoplasmosis. This study indicates that SAG1-VLP can be effectively utilized as a promising vaccine candidate for preventing or inhibiting T. gondii infection.

SUBMITTER: Choi WH

PROVIDER: S-EPMC7235809 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of <i>Toxoplasma gondii</i> as a Potential Vaccine Candidate for Toxoplasmosis.

Choi Won Hyung WH Park Ji Sun JS

Biomedicines 20200418 4

This study was carried out to evaluate the vaccination effect of a virus-like particle (VLP) including the surface antigen 1 (SAG1) of <i>Toxoplasma gondii</i> as a potential vaccine for toxoplasmosis. The SAG1 virus-like particles (SAG1-VLPs) were expressed by Sf9 cells, and their expression was confirmed through cloning, RT-PCR analysis, and western blot method. The immunogenicity and vaccine efficacy of SAG1-VLPs were assessed by the antibody response, cytokine analysis, neutralization activi ...[more]

PMID: 32325746

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Project description:Toxoplasmosis is a zoonotic disease caused by the obligate intracellular protozoan parasite T. gondii which is widely prevalent in humans and animals worldwide. The diagnosis of toxoplasmosis and distinguishing acute or chronic T. gondii infections have utmost importance for humans and animals. The TgSAG1, TgGRA7, and TgBAG1 proteins were used in the present study to develop the serological rSAG1-ELISA, rGRA7-ELISA and rBAG1-ELISA methods for the testing of T. gondii specific IgG and IgM antibodies and differentiating acute or chronic toxoplasmosis in 3733 animals, including Tibetan sheep, yaks, pigs, cows, cattle, horses, chickens, camels and donkeys from the Qinghai-Tibetan Plateau. The ELISA tests showed that the overall positivity of IgG antibody was 21.1% (786/3733), 15.3% (570/3733) and 18.2% (680/3733) for rSAG1-, rGRA7- and rBAG1-ELISA, respectively, and the positivity of IgM antibody was 11.8% (439/3733), 13.0% (486/3733) and 11.8% (442/3733) for rSAG1-, rGRA7- and rBAG1-ELISA, respectively. A total of 241 animals (6.5%) positive for all rSAG1-, rGRA7- and rBAG1-IgG were found in this study, and the 141 animals (3.8%) tested were anti-T. gondii IgM positive in all three ELISAs. Moreover, the 338, 284 and 377 animals were IgG positive in rSAG1 + rGRA7-, rBAG1 + rGRA7- and rSAG1 + rBAG1- ELISAs respectively, and the 346, 178 and 166 animals in rSAG1 + rGRA7-, rBAG1 + rGRA7- and rSAG1 + rBAG1-ELISAs were IgM positive respectively. The results confirmed that the application of SAG1, GRA7, and BAG1 recombinant antigens could successfully be used in the detection of specific IgG and IgM antibodies for distinguishing between acute or chronic T. gondii infections. It is inferred that the forms in which current animal species in the plateau area were infected with T. gondii, and the period of infection or the clinical manifestations of the current infections may be different. The present study provides substantial clinical evidence for the differential diagnosis of toxoplasmosis, and the classification of acute and chronic T. gondii infections.

Project description:BACKGROUND: Toxoplasmosis, caused by an obligate intracellular protozoan parasite Toxoplasma gondii, has been a serious clinical and veterinary problem. Effective DNA vaccines against T. gondii can prevent and control the spread of toxoplasmosis, which is important for both human health and the farming industry. The T. gondii 14-3-3 protein has been proved to be antigenic and immunogenic and was a potential vaccine candidate against toxoplasmosis. In this study, we evaluated the immune responses induced by recombinant plasmids encoding T. gondii surface antigen 1 (SAG1) and 14-3-3 protein by immunizing BALB/c mice intramuscularly. METHODS: In the present study, BALB/c mice were randomly divided into five groups, including three experimental groups (pSAG1, p14-3-3 and pSAG1/14-3-3) and two control groups (PBS and pBudCE4.1), and were immunized intramuscularly three times. The levels of IgG antibodies and cytokine production in mouse sera were determined by enzyme-linked immunosorbent assays (ELISA). Two weeks after the last immunization, all mice were challenged intraperitoneally (i.p.) with 1×10(4) tachyzoites of T. gondii and the survival time of mice was observed and recorded every day. RESULTS: Mice vaccinated with pSAG1, p14-3-3 or pSAG1/14-3-3 developed high levels of IgG2a and gamma interferon (IFN-?) and low levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) compared to control groups (PBS or pBudCE4.1), which suggested a modulated Th1 type immune response (P<0.05). After intraperitoneal challenge with 1×10(4) tachyzoites of T. gondii (RH strain), the survival time of mice in experimental groups was longer than control groups (P<0.05). Mouse immunized with pSAG1/14-3-3 induced a higher level of IgG antibody response and significantly prolonged the survival time when compared with pSAG1 or p14-3-3 (P<0.05). CONCLUSIONS: The study suggested that T. gondii 14-3-3 protein can induce effective immune responses in BALB/c mice and was a novel DNA vaccine candidate against toxoplasmosis, and the immune protective efficacy elicited by SAG1 gene was also demonstrated. Our results also showed multi-gene vaccine significantly enhanced immune responses and protective efficacy and was superior to the single-gene vaccine.

Dataset Information

Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of Toxoplasma gondii as a Potential Vaccine Candidate for Toxoplasmosis.

Publications

Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of <i>Toxoplasma gondii</i> as a Potential Vaccine Candidate for Toxoplasmosis.

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