Leishmania mexicana Gp63 cDNA Using Gene Gun Induced Higher Immunity to L. mexicana Infection Compared to Soluble Leishmania Antigen in BALB/C
,
Abstract
Background: Leishmaniasis is a worldwide disease prevalent in tropical and sub tropical countries. Many attempts have been made and different strategies have been approached to develop a potent vaccine against Leishmania. DNA immunisation is a method, which is shown to be effective in Leishmania vaccination. Leishmania Soluble Antigen (SLA) has also recently been used Leishmania vaccination.
Methods: The immunity generated by SLA and L. mexicana gp63 cDNA was compared in groups of 6 mice, which were statistically analysed by student t- test with the P-value of 0.05. SLA was administered by two different methods; intramuscular injection and injection of dendritic cells (DCs) loaded with SLA. L. mexicana gp63 cDNA was administered by the gene gun.
Results: Immunisation of BALB/c mice with L. mexicana gp63 resulted in high levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity, which were accompanied with protection induced by the immunisation against L. mexicana infection. In contrast, administration of SLA, produced a mixed Th1/Th2-type immune responses as well as a high level of CTL activity but did not protect mice from the infection.
Conclusion: The results indicate higher protection by DNA immunisation using L. mexicana gp63 cDNA compared to SLA, which is accompanied by a high level of Th1 immune response. However, the CTL activity does not necessarily correlate with the protection induced by the vaccine. Also, gene gun immunisation is a potential approach in Leishmania vaccination. These findings would be helpful in opening new windows in Leishmania vaccine research.
Herwaldt BL. Leishmaniasis. Lancet. 1999;, 354(9185):1191-1199.
Selvapandiyan A, Duncan R, Debrabant A, Lee N, SreenivasG, Salotra P, Nakhasi HL. Genetically modified live attenuated parasites as vaccines for leishmaniasis. Indian J Med Res. 2006; 123(3):455-466.
Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol. 2002; 14(1):103-110.
Sjolander A, Baldwin TM, Curtis JM, Handman E. Induction of a Th1 immune response and simultaneous lack of activation of a Th2 response are required for generation of immunity to leishmaniasis. J Immunol. 1998; 160(8):3949-3957.
Gurunathan S, Wu CY, Freidag BL, Seder RA. DNA vaccines: a key for inducing long-term cellular immunity. Curr Opin Immunol. 2000; 12(4):442-447.
Gurunathan S, Klinman DM, Seder RA. DNA vaccines: immunology, application, and optimization. Annu Rev Immunol. 2000; 18:927-974.
Lopez JA, Reins HA, Etges RJ, Button LL, McMasterWR, Overath P, Klein J. Genetic control of the immune response in mice to Leishmania mexicana surface protease. J Immunol. 1991; 146(4):1328-1334.
Russell DG, Alexander J. Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes. J Immunol. 1988; 140(4):1274-1279.
Dumonteil E, Maria Jesus RS, Javier EO, Maria del Rosario GM. DNA vaccines induce partial protection against Leishmania mexicana. Vaccine. 2003; 21(17-18):2161-2168.
Sharma SK, Dube A, Nadeem A, Khan S, Saleem I, Garg R, Mohammad O. Non PC liposome entrapped promastigote antigens elicit parasite specific CD8+ and CD4+ Tcell immune response and protect hamsters against visceral leishmaniasis. Vaccine. 2006; 24(11):1800-1810.
Gabaglia CR, Sercarz EE, Diaz-De-Durana Y, Hitt M, Graham FL, Gauldie J, Braciak TA. Life-long systemic protection in mice vaccinated with L. major and adenovirus IL-12 vector requires active infection, macrophages and intact lymph nodes. Vaccine. 2004; 23(2):247-257.
Ahuja SS, Reddick RL, Sato N, Montalbo E, Kostecki V, Zhao W, Dolan MJ, Melby PC, Ahuja SK. Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. J Immunol. 1999; 163(7):3890-3897.
Tegerstedt K, Franzen A, Ramqvist T, Dalianis T. Dendritic cells loaded with polyomavirus VP1/VP2Her2 virus-like particles efficiently prevent outgrowth of a Her2/neu expressing tumor. Cancer Immunol Immunother 2007; 56(9):1335-44.
Ghosh M, Pal C, RayM,Maitra S,Mandal L, Bandyopadhyay S. Dendritic cell-based immunotherapy combined with antimonybased chemotherapy cures established murine visceral leishmaniasis. J Immunol. 2003; 170(11):5625-5629.
Berberich C, Ramirez-Pineda JR, Hambrecht C, Alber G, Skeiky YA, Moll H. Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens. J Immunol. 2003; 170(6):3171-3179.
Moll H, Berberich C. Dendritic cell-based vaccination strategies: induction of protective immunity against leishmaniasis. Immunobiology. 2001, 204(5):659-666.
Bates PA. Complete developmental cycle of Leishmania mexicana in axenic culture. Parasitology. 1994; 108 ( Pt 1):1-9.
Inaba K, InabaM,RomaniN,AyaH,Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with gra-nulocyte/macrophage colony-stimulat-ing factor. J Exp Med. 1992; 176(6):1693-1702.
Kedzierski L, Zhu Y, Handman E. Leishmania vaccines: progress and problems. Parasitology. 2006; 133 Suppl:S87-S112.
Tewary P, Saxena S, Madhubala R. Coadministration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral leishmaniaisis. Vaccine. 2006; 24(13):2409-2416.
Walker PS, Scharton-Kersten T, Rowton ED, Hengge U, Bouloc A, Udey MC, Vogel JC. Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis. Hum Gene Ther. 1998; 9(13):1899-1907.
Sakai T, Hisaeda H, Nakano Y, Ishikawa H, Maekawa Y, Ishii K, Nitta Y, Miyazaki J, Himeno K. Gene gun-mediated delivery of an interleukin-12 expression plasmid protects against infections with the intracellular protozoan parasites Leishmania major and Trypanosoma cruzi in mice. Immunology. 2000; 99(4):615-624.
Da-Cruz AM, Conceicao-Silva F, Bertho AL, Coutinho SG. Leishmania-reactive CD4+ and CD8+ T cells associated with cure of human cutaneous leishmaniasis. Infect Immun. 1994; 62(6):2614-2618.
Gruber A, Chalmers AS, Rasmussen RA, Ong H, Popov S, Andersen J, Hu SL, Ruprecht RM. Dendritic Cell-Based Vaccine Strategy against Human Immunodeficiency Virus Clade C: Skewing The Immune Response TowardA Helper T Cell Type 2 Profile. Viral Immunol. 2007; 20(1):160-169.
Kamath AT, Feng CG, Macdonald M, Briscoe H, Britton WJ. Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis. Infect Immun. 1999; 67(4):1702-1707.
Da-Cruz AM, Bittar R,MattosM,Oliveira- Neto MP, Nogueira R, Pinho-Ribeiro V, Azeredo-Coutinho RB, Coutinho SG. Tcell- mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy. Clin Diagn Lab Immunol. 2002; 9(2):251-256.
Awasthi A, Mathur RK, Saha B. Immune response to Leishmania infection. Indian J Med Res. 2004; 119(6):238-258.
Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002; 2(11):845-858.
Liu L, Zhou X, Liu H, Xiang L, Yuan Z. CpG motif acts as a 'danger signal' and provides a T helper type 1-biased microenvironment for DNA vaccination. Immunology. 2005; 115(2):223-230.
Saldarriaga OA, Travi BL, Park W, Perez LE, Melby PC. Immunogenicity of a multicomponent DNA vaccine against visceral leishmaniasis in dogs. Vaccine. 2006; 24(11):1928-1940.
Feltquate DM, Heaney S, Webster RG, Robinson HL. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J Immunol. 1997; 158(5):2278-2284.
Schirmbeck R, Reimann J. Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by bacterial CpG motifs or IL-12. Intervirology. 2001; 44(2-3):115-123.
Zhou X, Zheng L, Liu L, Xiang L, Yuan Z. T helper 2 immunity to hepatitis B surface antigen primed by gene-gun-mediated DNA vaccination can be shifted towards T helper 1 immunity by codelivery of CpG motif-containing oligodeoxynucleotides. Scand J Immunol. 2003; 58(3):350-357.
Weiss R, Scheiblhofer S, Freund J, Ferreira F, Livey I, Thalhamer J. Gene gun bombardment with gold particles displays a particular Th2-promoting signal that overrules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines. Vaccine. 2002; 20(25-26):3148-3154.
Aberle JH, Aberle SW, Allison SL, Stiasny K, Ecker M, Mandl CW, Berger R, Heinz FX. A DNA immunization model study, with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms. J Immunol. 1999; 163(12):6756-6761.
Schmunis GA, Herman R. Characteristics of so-called natural antibodies in various normal sera against culture forms of Leishmania. J Parasitol. 1970; 56(5):889-896.
Nunes AC, Ramalho-Pinto FJ. Complement resistance of Leishmania amazonensis promastigotes is independent of parasite proteases and lysis of sensitive forms is not due to natural antibodies in normal human serum. Braz J Med Biol Res. 1996; 29(12):1633-1640.
| Files | ||
| Issue | Vol 6 No 4 (2011) | |
| Section | Articles | |
| Keywords | ||
| Leishmania mexicana Gene gun gp63 Leishmania Soluble Antigen BALB/c | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
