Protective efficacy of recombinant Toxoplasma gondii dense granule protein 15 against toxoplasmosis in C57BL/6 mice

被引:2
作者
Hasan, Tanjila [1 ,2 ]
Shimoda, Naomi [1 ]
Nakamura, Shu [1 ]
Fox, Barbara A. [3 ]
Bzik, David J. [3 ]
Ushio-Watanabe, Nanako [1 ]
Nishikawa, Yoshifumi [1 ]
机构
[1] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Inada-cho, Obihiro, Hokkaido 0808555, Japan
[2] Chattogram Vet & Anim Sci Univ, Fac Vet Med, Dept Med & Surg, Chattogram 4225, Bangladesh
[3] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, 1 Med Ctr Dr, Lebanon, NH 03756 USA
关键词
Toxoplasma gondii; Toxoplasmosis; GRA15; Recombinant vaccine; Immunostimulatory activity; IMMUNE-RESPONSE; INFECTION; EFFECTORS; GENOTYPE; ROP5;
D O I
10.1016/j.vaccine.2024.02.062
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toxoplasma gondii is a pervasive protozoan parasite that is responsible for significant zoonoses. A wide array of vaccines using different effector molecules of T. gondii have been studied worldwide to control toxoplasmosis. None of the existing vaccines are sufficiently effective to confer protective immunity. Among the different Toxoplasma-derived effector molecules, T. gondii dense granule protein 15 from the type II strain (GRA15 (II)) was recently characterized as an immunomodulatory molecule that induced host immunity via NF-kappa B. Therefore, we assessed the immunostimulatory and protective efficacy of recombinant GRA15 (II) (rGRA15) against T. gondii infection in a C57BL/6 mouse model. We observed that rGRA15 treatment increased the production of IL-12p40 from mouse peritoneal macrophages in vitro. Immunization of mice with rGRA15 induced the production of anti-TgGRA15-specific IgG, IgG1 and IgG2c antibodies. The rGRA15-sensitized spleen cells from mice inoculated with the same antigen strongly promoted spleen cell proliferation and IFN-gamma production. Immunization with rGRA15 significantly enhanced the survival rate of mice and dramatically decreased parasite burden in mice challenged with the Pru (type II) strain. These results suggested that rGRA15 triggered humoral and cellular immune responses to control infection. However, all of the immunized mice died when challenged with the GRA15-deficient Pru strain or the RH (type I) strain. These results suggest that GRA15 (II)-dependent immunity plays a crucial role in protection against challenge infection with the type II strain of T. gondii. This study is the first report to show GRA15 (II) as a recombinant vaccine antigen against Toxoplasma infection.
引用
收藏
页码:2299 / 2309
页数:11
相关论文
共 46 条
[1]   Drugs in development for toxoplasmosis: advances, challenges, and current status [J].
Alday, P. Holland ;
Doggett, Joseph Stone .
DRUG DESIGN DEVELOPMENT AND THERAPY, 2017, 11 :273-293
[2]   Ranking the Disease Burden of 14 Pathogens in Food Sources in the United States Using Attribution Data from Outbreak Investigations and Expert Elicitation [J].
Batz, Michael B. ;
Hoffmann, Sandra ;
Morris, J. Glenn, Jr. .
JOURNAL OF FOOD PROTECTION, 2012, 75 (07) :1278-1291
[3]   A COMMERCIAL VACCINE FOR OVINE TOXOPLASMOSIS [J].
BUXTON, D ;
INNES, EA .
PARASITOLOGY, 1995, 110 :S11-S16
[4]   DNA vaccination with genes encoding Toxoplasma gondii antigens ROP5 and GRA15 induces protective immunity against toxoplasmosis in Kunming mice [J].
Chen, Jia ;
Li, Zhong-Yuan ;
Petersen, Eskild ;
Huang, Si-Yang ;
Zhou, Dong-Hui ;
Zhu, Xing-Quan .
EXPERT REVIEW OF VACCINES, 2015, 14 (04) :617-624
[5]   Evaluation of long-term immunity and protection against T. gondii after immunization with multivalent recombinant chimeric T. gondii proteins [J].
Chyb, Maciej ;
Dziadek, Bozena ;
Dzitko, Katarzyna ;
Ferra, Bartlomiej Tomasz ;
Kawka, Malwina ;
Holec-Gasior, Lucyna ;
Gatkowska, Justyna .
SCIENTIFIC REPORTS, 2023, 13 (01)
[6]   Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection [J].
Denkers, EY ;
Gazzinelli, RT .
CLINICAL MICROBIOLOGY REVIEWS, 1998, 11 (04) :569-+
[7]   Economic and public health importance of Toxoplasma gondii infections in sheep: 2009-2020 [J].
Dubey, J. P. ;
Murata, F. H. A. ;
Cerqueira-Cezar, C. K. ;
Kwok, O. C. H. ;
Su, C. .
VETERINARY PARASITOLOGY, 2020, 286
[8]   Public health and economic importance of Toxoplasma gondii infections in goats: The last decade [J].
Dubey, J. P. ;
Murata, F. H. A. ;
Cerqueira-Cezar, C. K. ;
Kwok, O. C. H. .
RESEARCH IN VETERINARY SCIENCE, 2020, 132 :292-307
[9]  
Dubey JP., 2010, Toxoplasmosis of animals and humans, Vsecond, P336, DOI DOI 10.1201/9781420092370
[10]   Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice [J].
Dunay, Ildiko Rita ;
Gajurel, Kiran ;
Dhakal, Reshika ;
Liesenfeld, Oliver ;
Montoya, Jose G. .
CLINICAL MICROBIOLOGY REVIEWS, 2018, 31 (04)