PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis
Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa Toxoplasma gondii, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.619335/full |
| _version_ | 1819159934824087552 |
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| author | Jixu Li Jixu Li Jixu Li Eloiza May Galon Huanping Guo Mingming Liu Yongchang Li Shengwei Ji Iqra Zafar Yang Gao Weiqing Zheng Weiqing Zheng Paul Franck Adjou Moumouni Mohamed Abdo Rizk Mohamed Abdo Rizk Maria Agnes Tumwebaze Byamukama Benedicto Aaron Edmond Ringo Tatsunori Masatani Xuenan Xuan |
| author_facet | Jixu Li Jixu Li Jixu Li Eloiza May Galon Huanping Guo Mingming Liu Yongchang Li Shengwei Ji Iqra Zafar Yang Gao Weiqing Zheng Weiqing Zheng Paul Franck Adjou Moumouni Mohamed Abdo Rizk Mohamed Abdo Rizk Maria Agnes Tumwebaze Byamukama Benedicto Aaron Edmond Ringo Tatsunori Masatani Xuenan Xuan |
| author_sort | Jixu Li |
| collection | DOAJ |
| description | Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa Toxoplasma gondii, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication in vivo, severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Δgra9 in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Δgra9 vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-γ) and interleukin-12 (IL-12), maintained the high T. gondii-specific immunoglobulin G (IgG) level, and mixed high IgG1/IgG2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Δgra9 vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic T. gondii challenges. Together, Δgra9 vaccination provided safe and efficient immune protection against challenging parasites, suggesting that PLK:Δgra9 is a potentially promising live attenuated vaccine candidate. |
| first_indexed | 2024-12-22T16:48:27Z |
| format | Article |
| id | doaj.art-2c632fed770542b39be236e3f919a5db |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T16:48:27Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2c632fed770542b39be236e3f919a5db2022-12-21T18:19:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-03-011210.3389/fmicb.2021.619335619335PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic ToxoplasmosisJixu Li0Jixu Li1Jixu Li2Eloiza May Galon3Huanping Guo4Mingming Liu5Yongchang Li6Shengwei Ji7Iqra Zafar8Yang Gao9Weiqing Zheng10Weiqing Zheng11Paul Franck Adjou Moumouni12Mohamed Abdo Rizk13Mohamed Abdo Rizk14Maria Agnes Tumwebaze15Byamukama Benedicto16Aaron Edmond Ringo17Tatsunori Masatani18Xuenan Xuan19State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, ChinaCollege of Agriculture and Animal Husbandry, Qinghai University, Xining, ChinaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanThe Collaboration Unit for Field Epidemiology of State Key Laboratory for Infectious Disease Prevention and Control, Jiangxi Provincial key Laboratory of Animal-origin and Vector-borne Diseases, Nanchang Center for Disease Control and Prevention, Nanchang, ChinaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanDepartment of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanTransboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanToxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa Toxoplasma gondii, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication in vivo, severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Δgra9 in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Δgra9 vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-γ) and interleukin-12 (IL-12), maintained the high T. gondii-specific immunoglobulin G (IgG) level, and mixed high IgG1/IgG2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Δgra9 vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic T. gondii challenges. Together, Δgra9 vaccination provided safe and efficient immune protection against challenging parasites, suggesting that PLK:Δgra9 is a potentially promising live attenuated vaccine candidate.https://www.frontiersin.org/articles/10.3389/fmicb.2021.619335/fullToxoplasma gondiitoxoplasmosislive attenuated vaccinePLK:Δgra9protective immunity |
| spellingShingle | Jixu Li Jixu Li Jixu Li Eloiza May Galon Huanping Guo Mingming Liu Yongchang Li Shengwei Ji Iqra Zafar Yang Gao Weiqing Zheng Weiqing Zheng Paul Franck Adjou Moumouni Mohamed Abdo Rizk Mohamed Abdo Rizk Maria Agnes Tumwebaze Byamukama Benedicto Aaron Edmond Ringo Tatsunori Masatani Xuenan Xuan PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis Frontiers in Microbiology Toxoplasma gondii toxoplasmosis live attenuated vaccine PLK:Δgra9 protective immunity |
| title | PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis |
| title_full | PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis |
| title_fullStr | PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis |
| title_full_unstemmed | PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis |
| title_short | PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis |
| title_sort | plk δgra9 live attenuated strain induces protective immunity against acute and chronic toxoplasmosis |
| topic | Toxoplasma gondii toxoplasmosis live attenuated vaccine PLK:Δgra9 protective immunity |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.619335/full |
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