Complete Protection Against Lethal Toxoplasma Gondii Infection in Mice Immunized with a Plasmid Encoding the SAG1 Gene

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1999 Nov 24

PMID 10569750

Citations 32

Authors

H V Nielsen

S L Lauemoller

L Christiansen

S Buus

A Fomsgaard

E Petersen

Affiliations

Soon will be listed here.

Abstract

Infection with the protozoan parasite Toxoplasma gondii is transmitted to humans from infected animals by tissue cysts and oocysts excreted by cats. Immunization with inactivated parasites or recombinant proteins has at best shown partial protection. We constructed a plasmid expressing the SAG1 surface antigen of T. gondii, p1tPASAG1, and showed that animals immunized with the plasmid produce anti-SAG1 antibodies which recognize the native SAG1. Mice immunized with p1tPASAG1 showed 80 to 100% protection against challenge with the non-cyst-producing, virulent RH isolate, compared to an 80% mortality in mice immunized with empty plasmid, which is the greatest efficacy of any vaccine against T. gondii produced so far. The SAG1 molecule was analyzed for potential cytotoxic T-lymphocyte (CTL) epitopes, and four peptides with the best fit were synthesized. The ability of the peptides to stimulate gamma interferon production by CD8(+) T cells from p1tPASAG1-immunized mice was tested in an ELISPOT assay, and one new CTL epitope was identified. Adoptive transfer of CD8(+) T cells from p1tPASAG1-immunized to naïve mice showed partial protection. In conclusion, DNA vaccination with p1tPASAG1 gave effective protection in mice against T. gondii infection and the protection could be adoptively transferred by purified CD8(+) T cells.

Citing Articles

Protective efficacy of Toxoplasma gondii bivalent MAG1 and SAG1 DNA vaccine against acute toxoplasmosis in BALB/c mice.

Cao L, Liu J, Cao S, Zhao P, Sun X, Dong H Parasitol Res. 2023; 122(3):739-747.

PMID: 36600165 DOI: 10.1007/s00436-022-07745-8.

GRA15 DNA Vaccine with a Liposomal Nanocarrier Composed of an SS-Cleavable and pH-Activated Lipid-like Material Induces Protective Immunity against Toxoplasmosis in Mice.

Hasan T, Kawanishi R, Akita H, Nishikawa Y Vaccines (Basel). 2022; 10(1).

PMID: 35062682 PMC: 8781839. DOI: 10.3390/vaccines10010021.

Targeted Delivery of Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis.

Lakhrif Z, Moreau A, Herault B, Di-Tommaso A, Juste M, Moire N Front Immunol. 2018; 9:317.

PMID: 29515595 PMC: 5826183. DOI: 10.3389/fimmu.2018.00317.

Immune responses and protection after DNA vaccination against Toxoplasma gondii calcium-dependent protein kinase 2 (TgCDPK2).

Chen K, Wang J, Huang S, Yang W, Zhu W, Zhu X Parasite. 2017; 24:41.

PMID: 29119944 PMC: 5678354. DOI: 10.1051/parasite/2017045.

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against .

El Bissati K, Chentoufi A, Krishack P, Zhou Y, Woods S, Dubey J JCI Insight. 2016; 1(15):e85955.

PMID: 27699241 PMC: 5033759. DOI: 10.1172/jci.insight.85955.

References

Waldeland H, FRENKEL J . Live and killed vaccines against toxoplasmosis in mice. J Parasitol. 1983; 69(1):60-5. View

McMichael A, Hanke T . Is an HIV vaccine possible?. Nat Med. 1999; 5(6):612-4. DOI: 10.1038/9455. View

Buxton D, Uggla A, Lovgren K, Thomson K, Lunden A, Morein B . Trial of a novel experimental Toxoplasma iscom vaccine in pregnant sheep. Br Vet J. 1989; 145(5):451-7. DOI: 10.1016/0007-1935(89)90053-5. View

Suzuki Y, Remington J . The effect of anti-IFN-gamma antibody on the protective effect of Lyt-2+ immune T cells against toxoplasmosis in mice. J Immunol. 1990; 144(5):1954-6. View

Gazzinelli R, Hakim F, Hieny S, Shearer G, Sher A . Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol. 1991; 146(1):286-92. View

Parker S, Roberts C, Alexander J . CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice. Clin Exp Immunol. 1991; 84(2):207-12. PMC: 1535410. DOI: 10.1111/j.1365-2249.1991.tb08150.x. View

Buxton D, Thomson K, Maley S, Wright S, Bos H . Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant. Vet Rec. 1991; 129(5):89-93. DOI: 10.1136/vr.129.5.89. View

Bulow R, Boothroyd J . Protection of mice from fatal Toxoplasma gondii infection by immunization with p30 antigen in liposomes. J Immunol. 1991; 147(10):3496-500. View

Gazzinelli R, Xu Y, Hieny S, Cheever A, Sher A . Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol. 1992; 149(1):175-80. View

10.

Kim K, Bulow R, Kampmeier J, Boothroyd J . Conformationally appropriate expression of the Toxoplasma antigen SAG1 (p30) in CHO cells. Infect Immun. 1994; 62(1):203-9. PMC: 186087. DOI: 10.1128/iai.62.1.203-209.1994. View

11.

Shirahata T, Yamashita T, Ohta C, Goto H, Nakane A . CD8+ T lymphocytes are the major cell population involved in the early gamma interferon response and resistance to acute primary Toxoplasma gondii infection in mice. Microbiol Immunol. 1994; 38(10):789-96. DOI: 10.1111/j.1348-0421.1994.tb01858.x. View

12.

Roberts C, Brewer J, Alexander J . Congenital toxoplasmosis in the Balb/c mouse: prevention of vertical disease transmission and fetal death by vaccination. Vaccine. 1994; 12(15):1389-94. DOI: 10.1016/0264-410x(94)90147-3. View

13.

Buus S, Stryhn A, Winther K, Kirkby N, Pedersen L . Receptor-ligand interactions measured by an improved spun column chromatography technique. A high efficiency and high throughput size separation method. Biochim Biophys Acta. 1995; 1243(3):453-60. DOI: 10.1016/0304-4165(94)00172-t. View

14.

Lunden A . Immune responses in sheep after immunization with Toxoplasma gondii antigens incorporated into iscoms. Vet Parasitol. 1995; 56(1-3):23-35. DOI: 10.1016/0304-4017(94)00670-8. View

15.

Powers D, Manning M, Hanscome P, Pietrobon P . Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus vaccine in the elderly. J Infect Dis. 1995; 172(4):1103-7. DOI: 10.1093/infdis/172.4.1103. View

16.

Montoya J, Lowe K, Clayberger C, Moody D, Do D, Remington J . Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells. Infect Immun. 1996; 64(1):176-81. PMC: 173743. DOI: 10.1128/iai.64.1.176-181.1996. View

17.

Gazzinelli R, Wysocka M, Hieny S, Scharton-Kersten T, Cheever A, Kuhn R . In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J Immunol. 1996; 157(2):798-805. View

18.

Pertmer T, Roberts T, Haynes J . Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery. J Virol. 1996; 70(9):6119-25. PMC: 190634. DOI: 10.1128/JVI.70.9.6119-6125.1996. View

19.

Harning D, Spenter J, Metsis A, Vuust J, Petersen E . Recombinant Toxoplasma gondii surface antigen 1 (P30) expressed in Escherichia coli is recognized by human Toxoplasma-specific immunoglobulin M (IgM) and IgG antibodies. Clin Diagn Lab Immunol. 1996; 3(3):355-7. PMC: 170346. DOI: 10.1128/cdli.3.3.355-357.1996. View

20.

Stryhn A, Pedersen L, Romme T, Holm C, Holm A, Buus S . Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding. Eur J Immunol. 1996; 26(8):1911-8. DOI: 10.1002/eji.1830260836. View