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Phage-fused epitopes from Leishmania infantum used as immunogenic vaccines confer partial protection against Leishmania amazonensis infection

Published online by Cambridge University Press:  23 June 2015

LOURENA EMANUELE COSTA ,
MIGUEL ANGEL CHÁVEZ-FUMAGALLI ,
VIVIAN TAMIETTI MARTINS ,
MARIANA COSTA DUARTE ,
DANIELA PAGLIARA LAGE ,
MAYARA I. S. LIMA ,
NATHÁLIA CRISTINA DE JESUS PEREIRA ,
MANUEL SOTO ,
CARLOS ALBERTO PEREIRA TAVARES  and
LUIZ RICARDO GOULART
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LOURENA EMANUELE COSTA
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MIGUEL ANGEL CHÁVEZ-FUMAGALLI
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
VIVIAN TAMIETTI MARTINS
Affiliation:
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MARIANA COSTA DUARTE
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
DANIELA PAGLIARA LAGE
Affiliation:
Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MAYARA I. S. LIMA
Affiliation:
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil
NATHÁLIA CRISTINA DE JESUS PEREIRA
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MANUEL SOTO
Affiliation:
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain
CARLOS ALBERTO PEREIRA TAVARES
Affiliation:
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
LUIZ RICARDO GOULART
Affiliation:
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil Department of Medical Microbiology and Immunology, University of California-Davis, Davis, CA, USA
EDUARDO ANTONIO FERRAZ COELHO*
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
*
* Corresponding author. Laboratório de Biotecnologia Aplicada ao Estudo das Leishmanioses, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31·270-901 Belo Horizonte, Minas Gerais, Brazil. E-mail: eduardoferrazcoelho@yahoo.com.br
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Summary

Two mimotopes of Leishmania infantum identified by phage display were evaluated as vaccine candidates in BALB/c mice against Leishmania amazonensis infection. The epitope-based immunogens, namely B10 and C01, presented as phage-fused peptides; were used without association of a Th1 adjuvant, and they were administered isolated or in combination into animals. Both clones showed a specific production of interferon-gamma (IFN-γ), interleukin-12 (IL-12) and granulocyte/macrophage colony-stimulating factor (GM-CSF) after in vitro spleen cells stimulation, and they were able to induce a partial protection against infection. Significant reductions of parasite load in the infected footpads, liver, spleen, bone marrow and paws’ draining lymph nodes were observed in the immunized mice, in comparison with the control groups (saline, saponin, wild-type and non-relevant clones). Protection was associated with an IL-12-dependent production of IFN-γ, mediated mainly by CD8+ T cells, against parasite proteins. Protected mice also presented low levels of IL-4 and IL-10, as well as increased levels of parasite-specific IgG2a antibodies. The association of both clones resulted in an improved protection in relation to their individual use. More importantly, the absence of adjuvant did not diminish the cross-protective efficacy against Leishmania spp. infection. This study describes for the first time two epitope-based immunogens selected by phage display technology against L. infantum infected dogs sera, which induced a partial protection in BALB/c mice infected with L. amazonensis.

Keywords

Phage displaymimotopesvaccineleishmaniasisTh1 immune response
Type
Research Article
Information
Parasitology , Volume 142 , Issue 10 , September 2015 , pp. 1335 - 1347
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Copyright
Copyright © Cambridge University Press 2015 

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References

REFERENCES

Afonso, L. C. and Scott, P. (1993). Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis . Infection and Immunity 61, 2952–2959.Google Scholar
Afrin, F., Anam, K. and Ali, N. (2000). Induction of partial protection against Leishmania donovani by promastigotes antigens in negatively charged liposomes. Journal of Parasitology 89, 730–735.CrossRefGoogle Scholar
Alvar, J., Vélez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J. and De Boer, M. (2012). Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7, e35671.Google Scholar
Bacon, K. M., Hotez, P. J., Kruchten, S. D., Kamhawi, S., Bottazzi, M. E., Valenzuela, J. G. and Lee, B. Y. (2013). The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas. Vaccine 31, 480–486.Google Scholar
Barbas, C. F., Burton, D. R., Scott, J. K. and Silverman, G. J. (2001). Phage Display: A Laboratory Manual. Cold Spring Harbor Laboratory Press, New York.Google Scholar
Barbour, A. G. and Restrepo, B. I. (2000). Antigenic variation in vector-borne pathogens. Emerging Infectious Diseases 6, 449–457.Google Scholar
Barral, A., Pedral-Sampaio, D., Grimaldi, G., Momen, H., McMahon-Pratt, D., Ribeiro-de-Jesus, A., Almeida, R., Badaro, R., Barral-Netto, M., Carvalho, E. M. and Johnson, W. D. (1991). Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. American Journal of Tropical Medicine and Hygiene 44, 536–546.Google Scholar
Basu, R., Roy, S. and Walden, P. (2007). HLA class I-restricted T cell epitopes of the kinetoplastid membrane protein-11 presented by Leishmania donovani-infected human macrophages. The Journal of Infectious Diseases 195, 1373–1380.Google Scholar
Bazan, J., Całkosiñski, I. and Gamian, A. (2012). Phage display: a powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications. Human Vaccines and Immunotherapeutics 8, 1817–1828.Google Scholar
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, 7036–7045.Google Scholar
Borja-Cabrera, G. P., Santos, F. N., Bauer, F. S., Parra, L. E., Menz, I., Morgado, A. A., Soares, I. S., Batista, L. M. and Palatnik-de-Sousa, C. B. (2008). Immunogenicity assay of the Leishmune vaccine against canine visceral leishmaniasis in Brazil. Vaccine 26, 4991–4997.CrossRefGoogle ScholarPubMed
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Bruttin, A., Brüssow, H. and Bru, H. (2005). Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrobial Agents and Chemotherapy 49, 2874–2878.Google Scholar
Carrión, J., Nieto, A., Iborra, S., Iniesta, V., Soto, M., Folgueira, C., Abanades, D. R., Requena, J. M. and Alonso, C. (2006). Immunohistological features of visceral leishmaniasis in BALB/c mice. Parasite Immunology 28, 173–183.Google Scholar
Carrión, J., Folgueira, C. and Alonso, C. (2008). Immunization strategies against visceral leishmaniosis with the nucleosomal histones of Leishmania infantum encoded in DNA vaccine or pulsed in dendritic cells. Vaccine 26, 2537–2544.CrossRefGoogle ScholarPubMed
Cerpa-Cruz, S., Paredes-Casillas, P., Landeros Navarro, E., Bernard-Medina, A. G., Martínez-Bonilla, G. and Gutiérrez-Ureña, S. (2013). Adverse events following immunization with vaccines containing adjuvants. Immunologic Research 56, 299–303.Google Scholar
Chávez-Fumagalli, M. A., Costa, M. A. F., Oliveira, D. M., Ramírez, L., Costa, L. E., Duarte, M. C., Martins, V. T., Oliveira, J. S., Olortegi, C. C., Bonay, P., Alonso, C., Tavares, C. A. P., Soto, M. and Coelho, E. A. F. (2010). Vaccination with the Leishmania infantum ribosomal proteins induces protection in BALB/c mice against Leishmania chagasi and Leishmania amazonensis challenge. Microbes and Infection 12, 967–977.Google Scholar
Cherwonogrodzky, J. W., Barabé, N. D., Grigat, M. L., Lee, W. E., Poirier, R. T., Jager, S. J. and Berger, B. J. (2014). Thermostable cross-protective subunit vaccine against Brucella species. Clinical and Vaccine Immunology 21, 1681–1688.CrossRefGoogle ScholarPubMed
Clark, J. R. and March, J. B. (2004). Bacteriophage-mediated nucleic acid immunisation. FEMS Immunology and Medical Microbiology 40, 21–26.Google Scholar
Coelho, E. A. F., 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.Google Scholar
Coelho, V. T. S., Oliveira, J. S., Valadares, D. G., Chávez-Fumagalli, M. A., Duarte, M. C., Lage, P. S., Soto, M., Santoro, M. M., Tavares, C. A. P., Fernandes, A. P. and Coelho, E. A. F. (2012). Identification of proteins in promastigote and amastigote-like Leishmania using an immunoproteomic approach. PLoS Neglected Tropical Diseases 6, e1430.Google Scholar
Coomber, D. W. and Ward, R. L. (2001). Isolation of human antibodies against the central DNA binding domain of p53 from an individual with colorectal cancer using antibody phage display. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 7, 2802–2808.Google ScholarPubMed
Costa, C. H. N., Peters, N. C., Maruyama, S. R., de Brito, E. C., Santos, I. K. F. D. M., Ali, N., Brodskyn, C., Campos-Neto, A., Carvalho, E. M., Chang, K. P., Fernandes, A. P., Fujiwara, R., Gazzinelli, R., Goto, H., Grimaldi, G., Kaye, P., Kedzierski, L., Khamesipour, A., Maia, C., McMaster, W. R., Mendonça, S. C. F., Nakhasi, H. L., Piazza, F., Quinnell, R., Reis, A. B., Santos-Gomes, G., Shaw, J., Valenzuela, J., Walden, P. and Werneck, G. (2011). Vaccines for the leishmaniases: proposals for a research agenda. PLoS Neglected Tropical Diseases 5, e943.Google Scholar
Costa, L. E., Goulart, L. R., Pereira, N. C. J., Ingrid, M., Lima, S., Duarte, M. C., Martins, V. T., Lage, P. S., Menezes-Souza, D., Ribeiro, T. G., Melo, M. N., Fernandes, A. P., Soto, M., Alberto, C., Tavares, P., Fumagalli, M. A. C. and Ferraz, E. A. F. (2014). Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis. PLoS ONE 9, e110014.Google Scholar
Croft, S. L. and Coombs, G. H. (2003). Leishmaniasis: current chemotherapy and recent advances in the search for novel drugs. Trends in Parasitology 19, 502–508.Google Scholar
Cunha-Júnior, J. P., Silva, D. A. O., Silva, N. M., Souza, M. A., Souza, G. R. L., Prudencio, C. R., Pirovani, C. P., Cezar, M., Cascardo, J., Barbosa, B. F., Goulart, L. R. and Mineo, J. R. (2010). A4D12 monoclonal antibody recognizes a new linear epitope from SAG2A Toxoplasma gondii tachyzoites, identified by phage display bioselection. Immunobiology 215, 26–37.Google Scholar
Das, A. and Ali, N. (2012). Vaccine prospects of killed but metabolically active Leishmania against visceral leishmaniasis. Expert Review of Vaccines 11, 783–785.Google Scholar
Dey, R., Dagur, P. K., Selvapandiyan, A., Mc Coy, J. P., Salotra, P., Duncan, R. and Nakhasi, H. L. (2013). Live attenuated Leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in BALB/c mice. Journal of Immunology (Baltimore, MD.: 1950) 190, 2138–2149.CrossRefGoogle ScholarPubMed
Dumas, C., Muyombwe, A., Roy, G., Matte, C., Ouellette, M., Olivier, M. and Papadopoulou, B. (2003). Recombinant Leishmania major secreting biologically active granulocyte-macrophage colony-stimulating factor survives poorly in macrophages in vitro and delays disease development in mice. Infection and Immunity 71, 6499–6509.Google Scholar
Duthie, M. S., Raman, V. S., Piazza, F. M. and Reed, S. G. (2012). The development and clinical evaluation of second-generation leishmaniasis vaccines. Vaccine 30, 134–141.Google Scholar
Fernandes, A. P., Costa, M. M. S., Coelho, E. A. F., Michalick, M. S. M., Freitas, E., Melo, M. N., Tafuri, W. L., Resende, D. D. M., Hermont, V., Abrantes, C. D. F. and Gazzinelli, R. T. (2008). Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 26, 5888–5895.Google Scholar
Frenkel, D., Katz, O. and Solomon, B. (2000). Immunization against Alzheimer's beta-amyloid plaques via EFRH phage administration. Proceedings of the National Academy of Sciences of the United States of America 97, 11455–11459.Google Scholar
Gamage, L. N. A., Ellis, J. and Hayes, S. (2009). Immunogenicity of bacteriophage lambda particles displaying porcine Circovirus 2 (PCV2) capsid protein epitopes. Vaccine 27, 6595–6604.Google Scholar
Gao, J., Wang, Y., Liu, Z. and Wang, Z. (2010). Phage display and its application in vaccine design. Annals of Microbiology 60, 13–19.CrossRefGoogle Scholar
Garcez, L. M., Goto, H., Ramos, P. K., Brigido, M. D. C., Gomes, P. A. F., Souza, R. A., De Luca, P. M., Mendonça, S. C., Muniz, J. A. P. C. and Shaw, J. J. (2002). Leishmania (Leishmania) amazonensis-induced cutaneous leishmaniasis in the primate Cebus apella: a model for vaccine trials. International Journal for Parasitology 32, 1755–1764.Google Scholar
García, L., Jidy, M. D., García, H., Boris, L., Fernández, R., Año, G., Valmaseda, T., Suzarte, E., Ramírez, M., Pino, Y., Campos, J., Menéndez, J., González, D., González, I., Pérez, O., Serrano, T., Lastre, M., Miralles, F., Maestre, J. L., Pérez, J. L., Pérez, A., Marrero, K., Ledón, T., Garcı, L., Dı, M., Rodrı, B. L., Ramı, M., Mene, J., Valera, R., Gonza, et al. (2005). The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteer. Infection and Immunity 73, 3018–3024.Google Scholar
Goldenthal, K. L., Cavagnaro, J. A., Alving, C. R. and Vogel, F. R. (1993). National cooperative vaccine development working group. Safety evaluation of vaccine adjuvants. AIDS Research and Human Retroviruses 9, S45–S49.Google Scholar
Gomes, R., Teixeira, C., Teixeira, M. J., Oliveira, F., Menezes, M. J., Silva, C., Oliveira, C. I., Miranda, J. C., Elnaiem, D. E., Kamhawi, S., Valenzuela, J. G. and Brodskyn, C. I. (2008). Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proceedings of the National Academy of Sciences of the United States of America 105, 7845–7850.Google Scholar
Goto, Y., Bhatia, A., Raman, V. S., Liang, H., Mohamath, R., Picone, A. F., Vidal, S. E. Z., Vedvick, T. S., Howard, R. F. and Reed, S. G. (2011). KSAC, the first defined polyprotein vaccine candidate for visceral leishmaniasis. Clinical and Vaccine Immunology 18, 1118–1124.Google Scholar
Grimaldi, G. and Tesh, R. B. (1993). Leishmaniases of the New World: current concepts and implications for future research. Clinical Microbiology Reviews 6, 230–250.Google Scholar
Gu, Y., Li, J., Zhu, X., Yang, J., Li, Q., Liu, Z., Yu, S. and Li, Y. (2008). Trichinella spiralis: characterization of phage-displayed specific epitopes and their protective immunity in BALB/c mice. Experimental Parasitology 118, 66–74.CrossRefGoogle ScholarPubMed
Gumy, A., Louis, J. A. and Launois, P. (2004). The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds. International Journal for Parasitology 34, 433–444.Google Scholar
Hamad, M. (2011). Universal vaccines: shifting to one for many or shooting too high too soon! APMIS 119, 565–573.Google Scholar
Hardy, B. and Raiter, A. (2005). A mimotope peptide-based anti-cancer vaccine selected by BAT monoclonal antibody. Vaccine 23, 4283–4291.Google Scholar
Hashemi, H., Bamdad, T., Jamali, A., Pouyanfard, S. and Mohammadi, M. G. (2010). Evaluation of humoral and cellular immune responses against HSV-1 using genetic immunization by filamentous phage particles: a comparative approach to conventional DNA vaccine. Journal of Virological Methods 163, 440–444.Google Scholar
Heithoff, D. M., House, J. K., Thomson, P. C. and Mahan, M. J. (2015). Development of a Salmonella cross-protective vaccine for food animal production systems. Vaccine 33, 100–107.Google Scholar
Iborra, S., Parody, N., Abánades, D. R., Bonay, P., Prates, D., Novais, F. O., Barral-Netto, M., Alonso, C. and Soto, M. (2008). Vaccination with the Leishmania major ribosomal proteins plus CpG oligodeoxynucleotides induces protection against experimental cutaneous leishmaniasis in mice. Microbes and Infection 10, 1133–1141.Google Scholar
Kanduc, D., Stufano, A., Lucchese, G. and Kusalik, A. (2008). Massive peptide sharing between viral and human proteomes. Peptides 29, 1755–1766.CrossRefGoogle ScholarPubMed
Kyes, S. A., Kraemer, S. M. and Smith, J. D. (2007). Antigenic variation in Plasmodium falciparum: gene organization and regulation of the var multigene family. Eukaryotic Cell 6, 1511–1520.CrossRefGoogle ScholarPubMed
Lobigs, M. and Diamond, M. S. (2012). Feasibility of cross-protective vaccinations agains flaviviruses of the Japanese encephalitis serocomplex. Expert Reviews of Vaccines 11, 177–187.CrossRefGoogle Scholar
Manoutcharian, K. (2005). Bacteriophages as tools for vaccine and drug development. Expert Reviews of Vaccines 4, 5–7.Google Scholar
Manoutcharian, K., Gevorkian, G., Cano, A. and Almagro, J. C. (2001). Phage displayed biomolecules as preventive and therapeutic agents. Current Pharmaceutical Biotechnology 2, 217–223.CrossRefGoogle ScholarPubMed
Manoutcharian, K., Díaz-Orea, A., Gevorkian, G., Fragoso, G., Acero, G., González, E., De Aluja, A., Villalobos, N., Gómez-Conde, E. and Sciutto, E. (2004). Recombinant bacteriophage-based multiepitope vaccine against Taenia solium pig cysticercosis. Veterinary Immunology and Immunopathology 99, 11–24.Google Scholar
Margonari, C., Freitas, C. R., Ribeiro, R. C., Moura, A. C. M., Timbó, M., Gripp, A. H., Pessanha, J. E. and Dias, E. S. (2006). Epidemiology of visceral leishmaniasis through spatial analysis, in Belo Horizonte municipality, state of Minas Gerais, Brazil. Memórias do Instituto Oswaldo Cruz 101, 31–38.CrossRefGoogle Scholar
Martins, V. T., Chávez-Fumagalli, M. A., Costa, L. E., Martins, A. M. C. C., Lage, P. S., Lage, D. P., Duarte, M. C., Valadares, D. G., Magalhães, R. D. M., Ribeiro, T. G., Nagem, R. A. P., DaRocha, W. D., Regis, W. C. B., Soto, M., Coelho, E. A. F., Fernandes, A. P. and Tavares, C. A. P. (2013). Antigenicity and protective efficacy of a Leishmania amastigote-specific protein, member of the super-oxygenase family, against visceral leishmaniasis. PLoS Neglected Tropical Diseases 7, e2148.CrossRefGoogle ScholarPubMed
Minodier, P. and Parola, P. (2007). Cutaneous leishmaniasis treatment. Travel Medicine and Infectious Disease 5, 150–158.Google 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.CrossRefGoogle ScholarPubMed
Modabber, F. (2010). Leishmaniasis vaccines: past, present and future. International Journal of Antimicrobial Agents 36S, 58–61.Google Scholar
Moreno, J., Vouldoukis, I., Martin, V., McGahie, D., Cuisinier, A. M. and Gueguen, S. (2012). Use of a LiESP/QA-21 vaccine (CaniLeish) stimulates an appropriate Th1-dominated cell-mediated immuneresponse in dogs. PLoS Neglected Tropical Diseases 6, e1683.Google Scholar
Murray, H. W., Cervia, J. S., Hariprashad, J., Taylor, A. P., Stoeckle, M. Y. and Hockman, H. (1995). Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis. Journal of Clinical Investigation 95, 1183–1192.Google Scholar
Nico, D., Gomes, D. C., Alves-Silva, M. V., Freitas, E. O., Morrot, A., Bahia, D., Palatnik, M., Rodrigues, M. M. and Palatnik-de-Sousa, C. B. (2014). Cross-protective immunity to Leishmania amazonensis is mediated by CD4+ and CD8+ epitopes of Leishmania donovani nucleoside hydrolase terminal domains. Frontiers in Immunology 5, 1–10.Google Scholar
Noben-Trauth, N., Lira, R., Nagase, H., Paul, W. E. and Sacks, D. L. (2003). The relative contribution of IL-4 receptor signaling and IL-10 to susceptibility to Leishmania major . Journal of Immunology (Baltimore, MD, 1950) 170, 5152–5158.Google Scholar
O'Hagan, D. T. and Rappuoli, R. (2004). Novel approaches to vaccine delivery. Pharmaceutical Research 21, 1519–1530.Google Scholar
Pitcovsky, T. A., Mucci, J., Alvarez, P., Leguizamón, M. S., Burrone, O., Alzari, P. M. and Campetella, O. (2001). Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants. Infection and Immunity 69, 1869–1875.CrossRefGoogle ScholarPubMed
Pizza, M., Scarlato, V., Masignani, V., Giuliani, M. M., Aricò, B., Comanducci, M., Jennings, G. T., Baldi, L., Bartolini, E., Capecchi, B., Galeotti, C. L., Luzzi, E., Manetti, R., Marchetti, E., Mora, M., Nuti, S., Ratti, G., Santini, L., Savino, S., Scarselli, M., Storni, E., Zuo, P., Broeker, M., Hundt, E., Knapp, B., Blair, E., Mason, T., Tettelin, H., Hood, D. W., Jeffries, A. C. et al. (2000). Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science (New York, NY) 287, 1816–1820.Google Scholar
Ramírez, L., Santos, D. M., Souza, A. P., Coelho, E. A. F., Barral, A., Alonso, C., Escutia, M. R., Bonay, P., Oliveira, C. I. and Soto, M. (2013). Evaluation of immune responses and analysis of the effect of vaccination of the Leishmania major recombinant ribosomal proteins L3 or L5 in two different murine models of cutaneous leishmaniasis. Vaccine 31, 1312–1319.Google Scholar
Ramirez, L., Corvo, L., Duarte, M. C., Chávez-Fumagalli, M. a, Valadares, D. G., Santos, D. M., de Oliveira, C. I., Escutia, M. R., Alonso, C., Bonay, P., Tavares, C. A. P., Coelho, E. A. F. and Soto, M. (2014). Cross-protective effect of a combined L5 plus L3 Leishmania major ribosomal protein based vaccine combined with a Th1 adjuvant in murine cutaneous and visceral leishmaniasis. Parasites and Vectors 7, 3.Google Scholar
Real, F., Vidal, R. O., Carazzolle, M. F., Mondego, J. M. C., Costa, G. G. L., Herai, R. H., Würtele, M., de Carvalho, L. M., e Ferreira, R. C., Mortara, R. A., Barbiéri, C. L., Mieczkowski, P., Da Silveira, J. F., Briones, M. R. D. S., Pereira, G. A. G. and Bahia, D. (2013). The genome sequence of Leishmania (Leishmania) amazonensis: functional annotation and extended analysis of gene models. DNA Research 20, 567–581.Google Scholar
Reithinger, R., Dujardin, J.-C., Louzir, H., Pirmez, C., Alexander, B. and Brooker, S. (2007). Cutaneous leishmaniasis. The Lancet Infectious Diseases 7, 581–596.CrossRefGoogle ScholarPubMed
Requena, J. M., Iborra, S., Carrion, J., Alonso, C. and Soto, M. (2004). Recent advances in vaccines for leishmaniasis. Expert Opinion on Biological Therapy 4, 1505–1517.CrossRefGoogle ScholarPubMed
Riedel, S. (2005). Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University Medical Center) 18, 21–25.Google Scholar
Rosa, R., Marques, C., Rodrigues, O. R. and Santos-Gomes, G. M. (2007). Immunization with Leishmania infantum released proteins confers partial protection against parasite infection with a predominant Th1 specific immune response. Vaccine 25, 4525–4532.Google Scholar
Smith, G. P. and Petrenko, V. A. (1997). Phage display. Chemical Reviews 97, 391–410.CrossRefGoogle ScholarPubMed
Spitzer, N., Jardim, A., Lippert, D. and Olafson, R. W. (1999). Long-term protection of mice against Leishmania major with a synthetic peptide vaccine. Vaccine 17, 1298–1300.Google Scholar
Van der Vaart, J. M., Pant, N., Wolvers, D., Bezemer, S., Hermans, P. W., Bellamy, K., Sarker, S. A., Van der Logt, C. P. E., Svensson, L., Verrips, C. T., Hammarstrom, L. and Van Klinken, B. J. W. (2006). Reduction in morbidity of rotavirus induced diarrhoea in mice by yeast produced monovalent llama-derived antibody fragments. Vaccine 24, 4130–4137.CrossRefGoogle ScholarPubMed
Wagner, S., Hafner, C., Allwardt, D., Jasinska, J., Ferrone, S., Zielinski, C. C., Scheiner, O., Wiedermann, U., Pehamberger, H. and Breiteneder, H. (2005). Vaccination with a human high molecular weight melanoma-associated antigen mimotope induces a humoral response inhibiting melanoma cell growth in vitro . The Journal of Immunology 174, 976–982.Google Scholar
Wan, Y., Wu, Y., Bian, J., Wang, X. Z., Zhou, W., Jia, Z. C., Tan, Y. and Zhou, L. (2001). Induction of hepatitis B virus-specific cytotoxic T lymphocytes response in vivo by filamentous phage display vaccine. Vaccine 19, 2918–2923.Google Scholar
Wang, L. F. and Yu, M. (2004). Epitope identification and discovery using phage display libraries: applications in vaccine development and diagnostics. Current Drug Targets 5, 1–15.Google Scholar
World Health Organization (2010). Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases. World Health Organization Tech Rep Ser 949. WHO, Geneva.Google Scholar
Zanin, F. H. C., Coelho, E. A. F., Tavares, C. a P., Marques-da-Silva, E. A., Silva Costa, M. M., Rezende, S. A., Gazzinelli, R. T. and Fernandes, A. P. (2007). Evaluation of immune responses and protection induced by A2 and nucleoside hydrolase (NH) DNA vaccines against Leishmania chagasi and Leishmania amazonensis experimental infections. Microbes and Infection 9, 1070–1077.Google Scholar