Malaria is a global disease affecting a large portion of the world’s population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.
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Toxoplasma gondii is an intracellular parasitic organism affecting all warm-blooded vertebrates. Due to the unavailability of commercialized human T. gondii vaccine, many studies have been reported investigating the protective efficacy of pre-clinical T. gondii vaccines expressing diverse antigens. Careful antigen selection and implementing multifarious immunization strategies could enhance protection against toxoplasmosis in animal models. Although none of the available vaccines could remove the tissue-dwelling parasites from the host organism, findings from these pre-clinical toxoplasmosis vaccine studies highlighted their developmental potential and provided insights into rational vaccine design. We herein explored the progress of T. gondii vaccine development using DNA, protein subunit, and virus-like particle vaccine platforms. Specifically, we summarized the findings from the pre-clinical toxoplasmosis vaccine studies involving T. gondii challenge infection in mice published in the past 5 years.
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Influenza virus-like particles presenting
Toxoplasma gondii
dense granule protein 7 protect mice from lethal ME49 challenge
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Toxoplasma gondii ME49 infections are typically diagnosed by serological tests. However, serological diagnosis of RH strain-induced toxoplasmosis remains unknown. In order to develop seradiagnosis of above 2 kinds of infections, we generated recombinant virus-like particles (VLPs) displaying the T. gondii rhoptry protein 4 (ROP4) and evaluated their potential in T. gondii ME49 or RH strain infection diagnostics. Mice were orally infected with either the tachyzoites of T. gondii (RH) or cysts of T. gondii (ME49) at various dosages, and sera were collected at regular intervals. ELISA-based serological tests were performed to assess IgG, IgM, and IgA antibody responses against ROP4 VLP antigen and tissue lysate antigen (TLA). Compared to TLA, IgG, IgM, and IgA levels to ROP4 VLP antigen were significantly higher in the sera of T. gondii RH-infected mice 1 and 2 week post-infection (PI). T. gondii-specific IgG antibody was detected at 1, 2, 4, and 8 week PI in the T. gondii ME49-infected mice with infection dose-dependent manner. These results indicated that the ROP4 VLP antigen was highly sensitive antigens detecting T. gondii RH and ME49 antibodies at an early stage.
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Toxoplasmagondii can infect humans worldwide, causing serious diseases in pregnant women and immunocompromised individuals. T. gondii rhoptry protein 13 (ROP13) is known as one of the key proteins involved in host cell invasion. In this study, we generated virus-like particles (VLPs) vaccine expressing T. gondii rhoptry ROP13 and investigated VLPs vaccine efficacy in mice. Mice immunized with ROP13 VLPs vaccine elicited significantly higher levels of T. gondii-specific IgG, IgG1, IgG2a, and IgA antibody responses following boost immunization and challenge infection, whereas antibody inductions were insignificant upon prime immunization. Differing immunization routes resulted in differing antibody induction, as intranasal immunization (IN) induced greater antibody responses than intramuscular immunization (IM) after boost and challenge infection. IN immunization induced significantly higher levels of IgG and IgA antibody responses from feces, antibody-secreting cells (ASCs), CD4+ T, CD8+ T cells and germinal center B cell responses in the spleen compared to IM immunization. Compared to IM immunization, IN immunization resulted in significantly reduced cyst counts in the brain as well as lesser body weight loss, which contributed to better protection. All of the mice immunized through either route survived, whereas all na?ve control mice perished. These results indicate that the ROP13 VLPs vaccine could be a potential vaccine candidate against T. gondii infection.
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Toxoplasma gondii is a ubiquitous protozoan parasite responsible for causing toxoplasmosis. Preventive measures for toxoplasmosis are currently lacking and as such, development of novel vaccines are of urgent need. In this study, we generated 2 virus-like particles (VLPs) vaccines expressing T. gondii rhoptry protein 4 (ROP4) or rhoptry protein 18 (ROP18) using influenza matrix protein (M1) as a core protein. Mice were intranasally immunized with VLPs vaccines and after the last immunization, mice were challenged with ME49 cysts. Protective efficacy was assessed and compared by determining serum antibody responses, body weight changes and the reduction of cyst counts in the brain. ROP18 VLPs-immunized mice induced greater levels of IgG and IgA antibody responses than those immunized with ROP4 VLPs. ROP18 VLPs immunization significantly reduced body weight loss and the number of brain cysts in mice compared to ROP4 VLPs post-challenge. These results indicate that T. gondii ROP18 VLPs elicited better protective efficacy than ROP4 VLPs, providing important insight into vaccine design strategy.
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Evaluation of a DNA vector plasmid encoding a partial rop18 gene from toxoplasma gondii in domestic cats as a vaccine candidate Ana Flávia Minutti, João Pedro Sasse, Ana Clécia dos Santos Silva, Thais Agostinho Martins, Valentina Martinez, Beatriz de Souza Lima Nino, Fernando de Souza Rodrigues, Luiz Daniel de Barros, João Luis Garcia Vaccine.2025; 54: 126965. CrossRef
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A peptide originated from Toxoplasma gondii microneme 8 displaying serological evidence to differentiate recent from chronic human infection Silas Silva Santana, Vinícius Fernandes Paiva, Fernando Reis Carvalho, Heber Leão Silva Barros, Tamires Lopes Silva, Patrício Silva Cardoso Barros, Ana Cláudia Arantes Marquez Pajuaba, Geisa Baptista Barros, Reynaldo Dietze, Tiago Wilson Patriarca Mineo, Parasitology International.2021; 84: 102394. CrossRef
Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations Hae-Ji Kang, Ki-Back Chu, Min-Ju Kim, Hyunwoo Park, Hui Jin, Su-Hwa Lee, Eun-Kyung Moon, Fu-Shi Quan Pharmaceutics.2020; 12(10): 989. CrossRef
Previous Infection with Plasmodium berghei Confers Resistance to Toxoplasma gondii Infection in Mice Dong-Hun Lee, Ki-Back Chu, Hae-Ji Kang, Su-Hwa Lee, Fu-Shi Quan The Korean Journal of Parasitology.2019; 57(2): 93. CrossRef
Influenza Virus-Like Particles Presenting both Toxoplasma gondii ROP4 and ROP13 Enhance Protection against T. gondii Infection Hae-Ji Kang, Su-Hwa Lee, Min-Ju Kim, Ki-Back Chu, Dong-Hun Lee, Manika Chopra, Hyo-Jick Choi, Hyunwoo Park, Hui Jin, Fu-Shi Quan Pharmaceutics.2019; 11(7): 342. CrossRef
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Toxoplasma gondii infections occur throughout the world, and efforts are needed to develop various vaccine candidates expressing recombinant protein antigens. In this study, influenza matrix protein (M1) virus-like particles (VLPs) consisting of T. gondii rhoptry antigen 4 (ROP4 protein) were generated using baculovirus (rBV) expression system. Recombinant ROP4 protein with influenza M1 were cloned and expressed in rBV. SF9 insect cells were coinfected with recombinant rBVs expressing T. gondii ROP4 and influenza M1. As the results, influenza M1 VLPs showed spherical shapes, and T. gondii ROP4 protein exhibited as spikes on VLP surface under transmission electron microscopy (TEM). The M1 VLPs resemble virions in morphology and size. We found that M1 VLPs reacted with antibody from T. gondii-infected mice by western blot and ELISA. This study demonstrated that T. gondii ROP4 protein can be expressed on the surface of influenza M1 VLPs and the M1 VLPs containing T. gondii ROP4 reacted with T. gondii-infected sera, indicating the possibility that M1 VLPs could be used as a coating antigen for diagnostic and/or vaccine candidate against T. gondii infection.
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Detection of Toxoplasma gondii Infections using Virus-Like Particles Displaying T. gondii ROP4 Antigen Min-Ju Kim, Jie Mao, Hae-Ji Kang, Ki-Back Chu, Fu-Shi Quan The Korean Journal of Parasitology.2021; 59(6): 565. CrossRef
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Previous Infection with Plasmodium berghei Confers Resistance to Toxoplasma gondii Infection in Mice Dong-Hun Lee, Ki-Back Chu, Hae-Ji Kang, Su-Hwa Lee, Fu-Shi Quan The Korean Journal of Parasitology.2019; 57(2): 93. CrossRef
Virus-Like Particles Expressing Toxoplasma gondii Rhoptry Protein 18 Induces Better Protection Than Rhoptry Protein 4 against T. gondii Infection Hae-Ji Kang, Su-Hwa Lee, Ki-Back Chu, Dong-Hun Lee, Fu-Shi Quan The Korean Journal of Parasitology.2018; 56(5): 429. CrossRef
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