Identification of T. Gondii Epitopes, Adjuvants, and Host Genetic Factors That Influence Protection of Mice and Humans

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2010 Mar 30

PMID 20347630

Citations 36

Authors

Tze Guan Tan

Ernest Mui

Hua Cong

William H Witola

Alexandre Montpetit

Stephen P Muench

John Sidney

Jeff Alexander

Alessandro Sette

Michael E Grigg

Ajesh Maewal

Rima McLeod

Affiliations

Soon will be listed here.

Abstract

Toxoplasma gondii is an intracellular parasite that causes severe neurologic and ocular disease in immune-compromised and congenitally infected individuals. There is no vaccine protective against human toxoplasmosis. Herein, immunization of L(d) mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-gamma production from L(d)-restricted CD8(+) T cells in vitro and protected mice. CD8(+) T cell peptide epitopes from T. gondii dense granule proteins GRA 3, 6, 7, and Sag 1, immunogenic in humans for HLA-A02(+), HLA-A03(+), and HLA-B07(+) cells were identified. Since peptide repertoire presented by MHC class I molecules to CD8(+) T cells is shaped by endoplasmic reticulum-associated aminopeptidase (ERAAP), polymorphisms in the human ERAAP gene ERAP1 were studied and associate with susceptibility to human congenital toxoplasmosis (p<0.05). These results have important implications for vaccine development.

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References

Gulukota K, Sidney J, Sette A, Delisi C . Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol. 1997; 267(5):1258-67. DOI: 10.1006/jmbi.1997.0937. View

Ishioka G, Fikes J, Hermanson G, Livingston B, Crimi C, Qin M . Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. J Immunol. 1999; 162(7):3915-25. View

Lourenco E, Bernardes E, Silva N, Mineo J, Panunto-Castelo A, Roque-Barreira M . Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma gondii. Microbes Infect. 2006; 8(5):1244-51. DOI: 10.1016/j.micinf.2005.11.013. View

BenMohamed L, Krishnan R, Auge C, Primus J, Diamond D . Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses. Immunology. 2002; 106(1):113-21. PMC: 1782698. DOI: 10.1046/j.1365-2567.2002.01396.x. View

Ajzenberg D, Banuls A, Su C, Dumetre A, Demar M, Carme B . Genetic diversity, clonality and sexuality in Toxoplasma gondii. Int J Parasitol. 2004; 34(10):1185-96. DOI: 10.1016/j.ijpara.2004.06.007. View

Kim S, Karasov A, Boothroyd J . Bradyzoite-specific surface antigen SRS9 plays a role in maintaining Toxoplasma gondii persistence in the brain and in host control of parasite replication in the intestine. Infect Immun. 2007; 75(4):1626-34. PMC: 1865672. DOI: 10.1128/IAI.01862-06. View

Dubey J, Speer C, Shen S, Kwok O, Blixt J . Oocyst-induced murine toxoplasmosis: life cycle, pathogenicity, and stage conversion in mice fed Toxoplasma gondii oocysts. J Parasitol. 1997; 83(5):870-82. View

Sidney J, Peters B, Frahm N, Brander C, Sette A . HLA class I supertypes: a revised and updated classification. BMC Immunol. 2008; 9:1. PMC: 2245908. DOI: 10.1186/1471-2172-9-1. View

Hammer G, Kanaseki T, Shastri N . The final touches make perfect the peptide-MHC class I repertoire. Immunity. 2007; 26(4):397-406. DOI: 10.1016/j.immuni.2007.04.003. View

10.

Livingston B, Alexander J, Crimi C, Oseroff C, Celis E, Daly K . Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans. J Immunol. 1999; 162(5):3088-95. View

11.

Cesbron-Delauw M, Capron A . Excreted/secreted antigens of Toxoplasma gondii--their origin and role in the host-parasite interaction. Res Immunol. 1993; 144(1):41-4. DOI: 10.1016/s0923-2494(05)80096-3. View

12.

McLeod R, Boyer K, Karrison T, Kasza K, Swisher C, Roizen N . Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis. 2006; 42(10):1383-94. DOI: 10.1086/501360. View

13.

Speir J, Garcia K, Brunmark A, Degano M, Peterson P, Teyton L . Structural basis of 2C TCR allorecognition of H-2Ld peptide complexes. Immunity. 1998; 8(5):553-62. DOI: 10.1016/s1074-7613(00)80560-9. View

14.

Schild H, Deres K, Wiesmuller K, Jung G, Rammensee H . Efficiency of peptides and lipopeptides for in vivo priming of virus-specific cytotoxic T cells. Eur J Immunol. 1991; 21(11):2649-54. DOI: 10.1002/eji.1830211102. View

15.

Nielsen M, Lundegaard C, Lund O, Kesmir C . The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage. Immunogenetics. 2005; 57(1-2):33-41. DOI: 10.1007/s00251-005-0781-7. View

16.

Sette A, Sidney J, Livingston B, Dzuris J, Crimi C, Walker C . Class I molecules with similar peptide-binding specificities are the result of both common ancestry and convergent evolution. Immunogenetics. 2003; 54(12):830-41. DOI: 10.1007/s00251-002-0530-0. View

17.

Zeng W, Ghosh S, Lau Y, Brown L, Jackson D . Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J Immunol. 2002; 169(9):4905-12. DOI: 10.4049/jimmunol.169.9.4905. View

18.

Saeij J, Arrizabalaga G, Boothroyd J . A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence. Infect Immun. 2008; 76(6):2402-10. PMC: 2423105. DOI: 10.1128/IAI.01494-07. View

19.

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

20.

Tsunoda I, Sette A, Fujinami R, Oseroff C, Ruppert J, Dahlberg C . Lipopeptide particles as the immunologically active component of CTL inducing vaccines. Vaccine. 1999; 17(7-8):675-85. DOI: 10.1016/s0264-410x(98)00250-3. View