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Intranasal immunization with LACK-DNA promotes protective immunity in hamsters challenged with Leishmania chagasi

Published online by Cambridge University Press:  26 August 2011

DANIEL CLAUDIO DE OLIVEIRA GOMES ,
BEATRIZ LILIAN DA SILVA COSTA SOUZA ,
HERBERT LEONEL DE MATOS GUEDES ,
ULISSES GAZOS LOPES  and
BARTIRA ROSSI-BERGMANN
DANIEL CLAUDIO DE OLIVEIRA GOMES*
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, 29040-091, Vitória, ES, Brazil
BEATRIZ LILIAN DA SILVA COSTA SOUZA
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
HERBERT LEONEL DE MATOS GUEDES
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
ULISSES GAZOS LOPES
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
BARTIRA ROSSI-BERGMANN
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
*
*Corresponding author: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil. Tel/Fax: 55 (27) 33357210 and 55 (27) 33357207. E-mail: dgomes@ndi.ufes.br
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Summary

LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in protozoans of the genus Leishmania which is associated with the immunopathogenesis and susceptibility of BALB/c mice to L. major infection. Previously, we demonstrated that intranasal immunization with a plasmid carrying the LACK gene of Leishmania infantum (LACK-DNA) promotes protective immunity in BALB/c mice against Leishmania amazonensis and Leishmania chagasi. In the present study, we investigated the protective immunity achieved in hamsters intranasally vaccinated with 2 doses of LACK-DNA (30 μg). Compared with controls (PBS and pCI-neo plasmid), animals vaccinated with LACK-DNA showed significant reduction in parasite loads in the spleen and liver, increased lymphoproliferative response and increased nitric oxide (NO) production by parasite antigen-stimulated splenocytes. Furthermore, hamsters vaccinated with LACK-DNA presented high IgG and IgG2a serum levels when compared to control animals. Our results showed that intranasal vaccination with LACK-DNA promotes protective immune responses in hamsters and demonstrated the broad spectrum of intranasal LACK-DNA efficacy in different host species, confirming previous results in murine cutaneous and visceral leishmaniasis.

Keywords

Leishmania chagasihamsterLACK-DNAmucosal vaccine
Type
Research Article
Information
Parasitology , Volume 138 , Issue 14 , December 2011 , pp. 1892 - 1897
Copyright
Copyright © Cambridge University Press 2011

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References

REFERENCES

Arakawa, T., Komesu, A., Otsuki, H., Sattabongkot, J., Udomsangpetch, R., Matsumoto, Y., Tsuji, N., Wu, Y., Torii, M. and Tsuboi, T. (2005). Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum. Infection and Immunity 73, 7375–7380. doi: 10.1128/IAI.73.11.7375-7380.2005.CrossRefGoogle ScholarPubMed
Basu, R., Bhaumik, S., Basu, J. M., Naskar, K., De, T. and Roy, S. (2005). Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis. The Journal of Immunology 174, 7160–7171.CrossRefGoogle ScholarPubMed
Bertholet, S., Goto, Y., Carter, L., Bhatia, A., Howard, R. F., Carter, D., Coler, R. N., Vedvick, T. S. and Reed, S. G. (2009). Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine 27, 7036–45. doi: 10.1016/j.vaccine.2009.09.066.CrossRefGoogle ScholarPubMed
Bhattacharjee, S., Gupta, G., Bhattacharya, P., Adhikari, A., Majumdar, S. B. and Majumdar, S. (2009). Anti-iL-10 mAb protection against experimental visceral leishmaniasis via induction of Th1 cytokines and nitric oxide. Indian Journal Experimental Biology 47, 489–497.Google ScholarPubMed
Bhowmick, S., Ravindran, R. and Ali, N. (2007). Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response. Vaccine 29, 6544–6556. doi:10.1016/j.vaccine.2007.05.042.CrossRefGoogle Scholar
Chabot, S., Brewer, A., Lowell, G., Plante, M., Cyr, S., Burt, D. S. and Ward, B. J. (2005). A novel intranasal Protollin-based measles vaccine induces mucosal and systemic neutralizing antibody responses and cell-mediated immunity in mice. Vaccine 23, 1374–1383. doi: 10.1016/j.vaccine.2004.09.010.CrossRefGoogle ScholarPubMed
Coelho, E. A., Tavares, C. A., Carvalho, F. A., Chaves, K. F., Teixeira, K. N., Rodrigues, R. C., Charest, H., Matlashewski, G., Gazzinelli, R. T. and Fernandes, A. P. (2003). Immune responses induced by the Leishmania(Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection. Infection and Immunity 71, 3988–3994. doi: 10.1128/IAI.71.7.3988-3994.2003.CrossRefGoogle Scholar
Czerkinsky, C., Anjuere, F., McGhee, J. R., George-Chandy, A., Holmgren, J., Kieny, M. P., Fujiyashi, K., Mestecky, J. F., Pierrefite-Carle, V., Rask, C. and Sun, J. B. (1997). Mucosal immunity and tolerance: relevance to vaccine development. Immunological Reviews 170, 197–222.CrossRefGoogle Scholar
Fernandes, A. P., Costa, M. M., Coelho, E. A., Michalick, M. S., de Freitas, E., Melo, M. N., Luiz Tafuri, W., Resende, D. de M., Hermont, V., Abrantes, C. De. F and Gazzinelli, R. T. (2008). Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 29, 5888–5895. doi: 10.1016/j.vaccine.2008.05.095.CrossRefGoogle Scholar
Garg, R. and Dube, A. (2006). Animal models for vaccine studies for visceral leishmaniasis. Indian Journal of Medical Research. 123, 439–454.Google ScholarPubMed
Garg, R., Gupta, S. K., Tripathi, P., Hajela, K., Sundar, S., Naik, S. and Dube, A. (2006). Leishmania donovani: identification of stimulatory soluble antigenic proteins using cured human and hamster lymphocytes for their prophylactic potential against visceral leishmaniasis. Vaccine 24, 2900–2909. doi: 10.1016/j.vaccine.2005.12.053.CrossRefGoogle ScholarPubMed
Gifawesen, C. and Farrell, J. P. (1989). Comparison of T-cell responses in self-limiting versus progressive visceral Leishmania donovani infections in golden hamsters. Infection and Immunity 57, 3091–3096.CrossRefGoogle ScholarPubMed
Gomes, D. C. O., Pinto, E. F., de Melo, L. D., Lima, W. P., Larraga, V., Lopes, U. G. and Rossi-Bergmann, B. (2007). Intranasal delivery of naked DNA encoding the LACK antigen leads to protective immunity against visceral leishmaniasis in mice. Vaccine 25, 2168–2172. doi:10.1016/j.vaccine.2006.11.060.CrossRefGoogle ScholarPubMed
Gonzalez-Aseguinolaza, G., Taladriz, S., Marquet, A. and Larraga, V. (1999). Molecular cloning, cell localization and binding affinity to DNA replication proteins of the p36/LACK protective antigen from Leishmania infantum. European Journal of Biochemistry 259, 909–916.CrossRefGoogle ScholarPubMed
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1962). Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Analytical Biochemistry 126, 131–138.CrossRefGoogle Scholar
Holzmuller, P., Cavaleyra, M., Moreaux, J., Kovacic, R., Vincendeau, P., Papierok, G. and Lemesre, J. L. (2005). Lymphocytes of dogs immunised with purified excreted-secreted antigens of Leishmania infantum co-incubated with Leishmania infected macrophages produce IFN gamma resulting in nitric oxide-mediated amastigote apoptosis. Veterinary Immunology and Immunopathology 106, 247–257. doi:10.1016/j.vetimm.2005.03 001.CrossRefGoogle ScholarPubMed
Kulshrestha, A., Singh, R., Kumar, D., Negi, N. S. and Salotra, P. (2011). Antimony resistant clinical isolates of Leishmania donovani are susceptible to paromomycin and sitamaquine. Antimicrobial Agents and Chemotherapy 1, 0: AAC.00812-10v1.Google Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951). Protein measurement with Folin-phenol reagent. The Journal of Biological Chemistry 193, 265–275.CrossRefGoogle ScholarPubMed
Marques-da-Silva, E. A., Coelho, E. A., Gomes, D. C., Vilela, M. C., Masioli, C. Z., Tavares, C. A., Fernandes, A. P., Afonso, L. C. and Rezende, S. A. (2005). Intramuscular immunization with p36(LACK) DNA vaccine induces IFN-gamma production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge. Parasitology Research 98, 67–74. doi: 10.1007/s00436-005-0008-8.CrossRefGoogle Scholar
Mazumdar, T., Anam, K. and Ali, N. (2005). Influence of phospholipid composition on the adjuvanticity and protective efficacy of liposome-encapsulated Leishmania donovani antigens. The Journal of Parasitology 91, 269–274. doi: 10.1645/GE-356R1.CrossRefGoogle ScholarPubMed
Melby, P. C., Chandrasekar, B., Zhao, W. and Coe, J. E. (2001 a). The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-Like cytokine response. The Journal of Immunolology 166, 1912–1920.CrossRefGoogle Scholar
Melby, P. C., Yang, J., Zhao, W., Perez, L. E. and Cheng, J. (2001 b). Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infection and Immunity 69, 4719–4725. doi: 10.1128/IAI.69.8.4719-4725.2001.CrossRefGoogle Scholar
Mizbani, A., Taheri, T., Zahedifard, F., Taslimi, Y., Azizi, H., Azadmanesh, K., Papadopoulou, B. and Rafati, S. (2009). Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis. Vaccine 28, 53–62. doi: 10.1016/j.vaccine.2009.09.114.CrossRefGoogle ScholarPubMed
Okwor, I. and Uzonna, J. (2008). Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies. Immunological Research 41, 123–136. doi: 10.1007/s12026-008-8016-2.CrossRefGoogle ScholarPubMed
Oliveira, L. F., Schubach, A. O., Martins, M. M., Passos, S. L., Oliveira, R. V., Marzochi, M. C. and Andrade, C. A. (2011). Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Tropica 118, 87–96. doi: 10.1016/j.actatropica.2011.02 007.CrossRefGoogle ScholarPubMed
Pinheiro, R. O., Pinto, E. F., de Matos Guedes, H. L., Filho, O. A., de Mattos, K. A., Saraiva, E. M., de Mendonça, S. C. and Rossi-Bergmann, B. (2007). Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan. Vaccine 25, 2716–22. doi: 10.1016/j.vaccine.2006.05.093.CrossRefGoogle ScholarPubMed
Pinto, E. F., Pinheiro, O. R., Rayol, A., Larraga, V. and Rossi-Bergmann, B. (2004). Intranasal vaccination agaist cutaneous leishmaniasis using a particulated leishmanial antigen or LACK-DNA. Infection and Immunity 72, 4521–4527. doi: 10.1128/IAI.72.8.4521-4527.2004.CrossRefGoogle Scholar
Romero, G. A. and Boelaert, M. (2010). Control of visceral leishmaniasis in Latin America-a systematic review. PLoS Negleted Tropical Disease 19, e584. doi: 10.1371/journal.pntd.0000584.CrossRefGoogle Scholar
Takagi, H., Hiroi, T., Yang, L. J., Tada, Y., Yuki, Y., Takamura, K., Ishimitsu, R., Kawauchi, H., Kiyono, H. and Takaiwa, F. A. (2005). Rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proceedings of the National Academy of Sciences, USA 102, 17525–17530. doi: 10.1073/pnas.0503428102.CrossRefGoogle ScholarPubMed
Tewary, P., Sukumaran, B., Saxena, S. and Madhubala, R. (2004). Immunostimulatory oligodeoxynucleotides are potent enhancers of protective immunity in mice immunized with recombinant ORFF leishmanial antigen. Vaccine 13, 3053–3060. doi:10.1016/j.vaccine.2004.02.007.CrossRefGoogle Scholar
Vélez, I. D., Gilchrist, K., Arbelaez, M. P., Rojas, C. A., Puerta, J. A., Antunes, C. M., Zicker, F. and Modabber, F. (2005). Failure of a killed Leishmania amazonensis vaccine against American cutaneous leishmaniasis in Colombia. Transactions of the Royal Society of Tropical Medicine and Hygiene 99, 593–598. doi: 10.1016/j.trstmh.2005.04.002.CrossRefGoogle ScholarPubMed