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Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis

Published online by Cambridge University Press:  19 July 2012

DANIEL CLÁUDIO DE OLIVEIRA GOMES*
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil Laboratório de Imunologia Celular e Molecular, Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, 29040-091, Vitória, ES, Brazil
RODRIGO PORTO SCHWEDERSKY
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
LUIZ DIONE BARBOSA DE-MELO
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil Laboratório de Genética Molecular, Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro, 20270-021, Rio de Janeiro, RJ, Brazil
BEATRIZ LILIAN DA SILVA COSTA SOUZA
Affiliation:
Laboratório de Imunofarmacologia, 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:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
ULISSES GAZOS LOPES
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
BARTIRA ROSSI-BERGMANN
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
*
*Corresponding author: Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil. Tel/Fax: +55 27 3335 7210 and +55 27 3335 7268. E-mail: [email protected]

Summary

LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in the protozoan of the genus Leishmania, which is associated with the immunopathogenesis and susceptibility of BALB/c mice to Leishmania major infection. We previously demonstrated that intranasal immunization with a plasmid DNA encoding the p36/LACK leishmanial antigen (pCI-neo-LACK) followed by challenge 7 days after a booster dose effectively protects BALB/c mice against both cutaneous and visceral leishmaniasis. In the present study, the correlation between systemic mRNA expression after nasal DNA uptake, and the duration of protective immunity was addressed. LACK mRNA transcripts were detected in the spleen, brain, cervical lymph nodes and popliteal lymph nodes as early as 7 days, lasting 3 months after vaccination with pCI-neo-LACK. The kinetics of transcript expression correlated with enhanced cutaneous hypersensitivity against parasite antigens. Leishmania chagasi infection at 7 days or 3 months, but not 6 months after vaccination resulted in significantly lower parasite loads as compared with non-vaccinated controls. Protection also correlated with enhanced spleen cell responsiveness to parasite antigens leading to increased IFN- γ and IL-4 and decreased IL-10 production. Together, these data demonstrate that the protection conferred by the intranasal DNA vaccine lasts at least 3 months and is associated with expression of vaccine mRNA in peripheral organs.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

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References

REFERENCES

Aebischer, T., Moody, S. F. and Handman, E. (1993). Persistence of virulent leishmania major in murine cutaneous leishmaniasis: A possible hazard for the host. Infection and Immunity 61, 220226.CrossRefGoogle ScholarPubMed
Alexander, J., Carter, K. C., Al-Fasi, N., Satoskar, A. and Brombacher, F. Endogenous (2000). IL-4 is necessary for effective drug therapy against visceral leishmaniasis. European Journal of Immunology 30, 29352943. doi: 10.1002/1521-4141(200010)30:10 < 2935::AID-IMMU2935 > 3.0.CO;2-Q.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Asanuma, H., Fujihashi, K., Miyakoshi, T., Yoshikawa, T., Fujita-Yamaguchi, Y., Kojima, N., Nakata, M., Suzuki, Y., Tamura, S., Kurata, T. and Sata, T. (1986). Long- and short-time immunological memory in different strains of mice given nasally an adjuvant-combined nasal influenza vaccine. Vaccine 25, 69756980. doi: 10.1016/j.vaccine.2007.06.060.CrossRefGoogle Scholar
Badaro, R., Jones, T. C., Carvalho, E. M., Sampaio, D., Reed, S. G. and Barral, A. (1986). New perspectives on a subclinical form of visceral leishmaniasis. Journal of Infectious Diseases 154, 10031011. doi: 10.1093/infdis/154.6.1003.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, 71607171.CrossRefGoogle ScholarPubMed
Benhnini, F., Chenik, M., Laouini, D., Louzir, H., Cazenave, P. A. and Dellagi, K. (2009). Comparative evaluation of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection in four inbred mouse strains. Clinical and Vaccine Immunology 16, 15291537. doi: 10.1128/CVI.00153-09.CrossRefGoogle ScholarPubMed
Carvalho, E. M., Teixeira, R. S. and Johnson, W. D. Jr. (1981). Cell-mediated immunity in American visceral leishmaniasis: reversible immunosuppression during acute infection. Infection and Immunity 981, 498500.CrossRefGoogle Scholar
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, 39883994. doi: 10.1128/IAI.71.7.3988-3994.2003.CrossRefGoogle Scholar
Cummings, H. E., Tuladhar, R. and Satoskar, A. R. (2010). Cytokines and Their STATs in Cutaneous and Visceral Leishmaniasis. Journal of Biomedicine and Biotechnology, 294389. doi: 10.1155/2010/294389.CrossRefGoogle ScholarPubMed
Feunou, P. F., Kammoun, H., Debrie, A. S., Mielcarek, N. and Locht, C. (2010). Long-term immunity against pertussis induced by a single nasal administration of live attenuated B. pertussis BPZE1. Vaccine 28, 7047–53. doi:10.1016/j.vaccine.2010.08.017.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, 21682172. 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, 909916.CrossRefGoogle ScholarPubMed
Gonzalo, R. M., del Real, G., Rodriguez, J. R., Rodriguez, D., Heljasvaara, R., Lucas, P., Larraga, V. and Esteban, M. (2002). A heterologous prime-boost regime using DNA and recombinant vaccinia virus expressing the Leishmania infantum P36/LACK antigen protects BALB/c mice from cutaneous leishmaniasis. Vaccine 20, 12261231. doi: 10.1016/S0264-410X(01)00427-3.CrossRefGoogle ScholarPubMed
Guan, J., Wen, B., Deng, Y., Zhang, K., Chen, H., Wu, X., Ruan, L. and Tan, W. (2011). Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes. Virology Journal 4, 506. doi: 10.1186/1743-422X-8-506.CrossRefGoogle Scholar
Han, I., Kim, M. Y., Byun, M., Hwang, T., Kim, J. M., Hwang, K. W., Park, T. G., Jung, W., Chun, T., Jeong, G. and Oh, Y. (2007). Enhanced brain targeting efficiency of intranasally administered plasmid DNA: an alternative route for brain gene therapy. Journal of Molecular Medicine 85, 7583. doi: 10.1007/s00109-006-0114-9.CrossRefGoogle ScholarPubMed
Julia, V. and Glaichenhaus, N. (1999). CD4 (+) T cells which react to the Leishmania major LACK antigen rapidly secrete interleukin-4 and are detrimental to the host in resistant B10-D2 mice. Infection and Immunity 67, 36413644.CrossRefGoogle Scholar
Liu, C., Fan, M. W., Xu, Q. G. and Li, Y. H. (2008). Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in mice. Journal of Gene Medicine 10, 298305. doi: 10.1002/jgm.1138.CrossRefGoogle ScholarPubMed
Kaye, P. M. and Aebischer, T. (2011). Visceral leishmaniasis: immunology and prospects for a vaccine. Clinical Microbiology and Infection 17, 1462–70. doi: 10.1111/j.1469-0691.2011.03610.x.CrossRefGoogle ScholarPubMed
Koutsonanos, D. G., Vassilieva, E. V., Stavropoulou, A., Zarnitsyn, V. G., Esser, E. S., Taherbhai, M. T., Prausnitz, M. R., Compans, R. W. and Skountzou, I. (2012). Delivery of subunit influenza vaccine to skin with microneedles improves immunogenicity and long-lived protection. Surface Science Reports 2, 357. doi: 10.1038/srep00357.Google ScholarPubMed
Locksley, R. M., Heinzel, F. P., Holaday, B. J., Mutha, S. S., Reiner, S. L. and Sadick, M. D. (1991). Induction of Th1 and Th2 CD4+ subsets during murine Leishmania major infection. Research in Immunology 142, 2832.CrossRefGoogle ScholarPubMed
Marques-Da-Silva, E. A., Coelho, E. A. F., Gomes, D. C. O., 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- production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge. Parasitology Research 98, 6774. doi: 10.1007/s00436-005-0008-8.CrossRefGoogle Scholar
Matsuo, K., Koizumi, H., Akashi, M., Nakagawa, S., Fujita, T., Yamamoto, A. and Okada, N. (2011). Intranasal immunization with poly(γ-glutamic acid) nanoparticles entrapping antigenic proteins can induce potent tumor immunity. Journal of Controlled Release 10, 310316. doi: 10.1016/j.jconrel.2011.03.009.CrossRefGoogle Scholar
McSorley, S. J., Rask, C., Pichot, R., Julia, V., Czerkinsky, C. and Glaichenhaus, N. (1998). Selective tolerization of Th1-like cells after nasal administration of a cholera toxoid-LACK conjugate. European Journal of Immunology 28, 424432. doi: 10.1002/(SICI)1521-4141(199802)28:02 < 424::AID-IMMU424 > 3.0.CO;2-U.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Melby, P. C., Yang, J., Zhao, W., Perez, L. E. and Cheng, J. (2001). Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infection and Immunity 69, 47194725. doi: 10.1128/IAI.69.8.4719-4725.2001.CrossRefGoogle Scholar
Mendez, S., Belkaid, Y., Seder, R. A. and Sacks, D. (2002). Optimization of DNA vaccination against cutaneous leishmaniasis. Vaccine 20, 37023708. doi: 10.1016/S0264-410X(02)00376-6.CrossRefGoogle ScholarPubMed
Mendez, S., Reckling, S. K., Piccirillo, C. A., Sacks, D. and Belkaid, Y. (2004). Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. The Journal of Experimental Medicine. 19, 201210. doi: 10.1084/jem.20040298.CrossRefGoogle Scholar
Mochly-Rosen, D., Khaner, H. and Lopez, J. (1991). Identification of intracellular receptor proteins for activated protein kinase C. Proceedings of the National Academy of Sciences, USA 88, 39974000.CrossRefGoogle ScholarPubMed
Muller, I. (1992). Role of T cell subsets during the recall of immunologic memory to Leishmania major. European Journal of Immunology 22, 30633069. doi: 10.1002/eji.1830221206.CrossRefGoogle ScholarPubMed
Oh, Y., Kim, J., Hwang, T. S., Ko, J. J., Kim, J. M., Yang, J. and Kim, C. (2003). Nasal absortion and biodistribution of plasmid DNA: an alternative route of DNA vaccine delivery. Vaccine 19, 4519–25. doi: 10.1016/S0264-410X(01)00188-8.CrossRefGoogle Scholar
Okuno, T., Takeuchi, M., Matsumoto, Y., Otsuka, H. and Matsumoto, Y. (2002). Pretreatment of Leishmania homologue of receptors for activated C kinase (LACK) promotes disease progression caused by Leishmania amazonensis. Experimental Animal 51, 335341. doi:10.1538/expanim.51.335.CrossRefGoogle ScholarPubMed
Pinheiro, R. O., Pinto, E. F., Guedes, H. L. M., Agrellos, A. O., de Mattos, K. A., Saraiva, E. M., De Mendonca, S. C. F. and Rossi-Bergmann, B. (2007). Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan. Vaccine 25, 27162722. doi:10.1016/j.vaccine.2006.05.093.CrossRefGoogle ScholarPubMed
Pinto, E. F., Cortezia, M. D. and Rossi-Bergmann, B. (2003). Interferon-gamma-inducing oral vaccination with Leishmania amazonensis antigens protects BALB/c and C57BL/6 mice against cutaneous leishmaniasis. Vaccine 21, 35343541. doi: 10.1016/S0264-410X(03)00427-4.CrossRefGoogle ScholarPubMed
Pinto, E. F., Pinheiro, R. O., Rayol, A., Larraga, V. and Rossi-Bergmann, B. (2004). Intranasal vaccination against cutaneous leishmaniasis using a particulated leishmanial antigen or DNA encoding LACK. Infection and Immunity 72, 4521–27. 10.1128/IAI.72.8.4521-4527.2004.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
Ramos, I., Alonso, A., Marcen, J. M., Peris, A., Castillo, J. A., Colmenares, M. and Larraga, V. (2008). Heterologous prime-boost vaccination with a non-replicative vaccinia recombinant vector expressing LACK confers protection against canine visceral leishmaniasis with a predominant Th1-specific immune response. Vaccine 26, 333344. doi: 10.1016/S0264-410X(03)00427-4.CrossRefGoogle ScholarPubMed
Sacks, D. and Noben-Trauth, N. (2002). The immunology of susceptibility and resistance to leishmania major in mice. Nature Reviews Immunology 2, 845858. doi: 10.1038/nri933.CrossRefGoogle ScholarPubMed
Sakai, S., Takashima, Y., Matsumoto, Y., Reed, S. G., Hayashi, Y. and Matsumoto, Y. (2010). Intranasal immunization with Leish-111f induces IFN- production and protects mice from Leishmania major infection. Vaccine 28, 22072213. doi: 10.1016/j.vaccine.2009.12.055.CrossRefGoogle ScholarPubMed
Sassi, A., Louzir, H., Ben Salah, A., Mokni, M., Ben Osman, A. and Dellagi, K. (1999). Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic leishmania major infection in Tunisia. Clinical and Experimental Immunology 116, 127132. 10.1046/j.1365-2249.1999.00844.x.CrossRefGoogle ScholarPubMed
Suter, T., Biollaz, G., Gatto, D., Bernasconi, L., Herren, T., Reith, W. and Fontana, A. (2003). The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation. European Journal of Immunology 33, 29983006. doi: 10.1002/eji.200323611.CrossRefGoogle ScholarPubMed
Takami, A., Masanori, B. and Mitsuru, A. (2012). Biodegradable nanoparticles as vaccine adjuvants and delivery systems: Regulation of immune responses by nanoparticle-based vaccine. Advances in Polymer Science 247, 3164. doi: 10.1007/12_2011_150.Google Scholar
Tang, J., Yin, R., Tian, Y., Huang, Z., Shi, J., Fu, X., Wang, L., Wu, Y., Hao, F. and Ni, B. (2011). A novel self-assembled nanoparticle vaccine with HIV-1 Tat49–57/HPV16 E749–57 fusion peptide and GM-CSF DNA elicits potent and prolonged CD8+ T cell-dependent anti-tumor immunity in mice. Vaccine 30, 10711082. doi:10.1016/j.vaccine.2011.12.029.CrossRefGoogle ScholarPubMed