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Sustained release of recombinant surface antigen 2 (rSAG2) from poly(lactide-co-glycolide) microparticles extends protective cell-mediated immunity against Toxoplasma gondii in mice

Published online by Cambridge University Press:  18 July 2014

SHU-CHUN CHUANG  and
CHUNG-DA YANG
SHU-CHUN CHUANG
Affiliation:
Department of Physiology, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
CHUNG-DA YANG*
Affiliation:
Graduate Institute of Animal Vaccine Technology, National Pingtung University of Science and Technology, No. 1, Shuefu Road, Neipu, Pingtung 912, Taiwan
*
*Corresponding author: Graduate Institute of Animal Vaccine Technology, National Pingtung University of Science and Technology, No. 1, Shuefu Road, Neipu, Pingtung 912, Taiwan. E-mail: [email protected]
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Summary

Current development efforts of subunit vaccines against Toxoplasma gondii, the aetiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigens (SAGs) such as SAG2, due to their attachment roles in the process of host-cell invasion. In the present study, we aimed to produce poly(lactide-co-glycolide) (PLG) microparticles (MPs) containing recombinant SAG2 (rSAG2) to induce improved immunity against T. gondii. The resulting PLG-encapsulated rSAG2 (PLG-rSAG2) MPs, 2·14–3·63 μm in diameter, showed 74–80% entrapment efficiency and gradually released antigenic rSAG2 protein (88·3% of the total protein load) for a long 33-day period. Peritoneal immunization with PLG-rSAG2 MPs in BALB/c mice resulted in not only sustained (10 weeks) lymphocyte proliferation and IFN-γ production but also an improved protective capacity (87%) against a lethal subcutaneous challenge of 1×104 live tachyzoites of T. gondii (RH strain). In conclusion, the sustained release of rSAG2 protein from PLG-rSAG2 MPs extends Th1 cell-mediated immunity (lymphocyte proliferation and IFN-γ production) and induces improved protection against T. gondii tachyzoite infection in mice.

Keywords

Toxoplasma gondii (T. gondii)recombinant SAG2 (rSAG2)cell-mediated immunitypoly(lactide-co-glycolide) (PLG)PLG-encapsulated rSAG2 microparticles (PLG-rSAG2 MPs)
Type
Research Article
Information
Parasitology , Volume 141 , Issue 12 , October 2014 , pp. 1657 - 1666
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Copyright
Copyright © Cambridge University Press 2014 

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References

REFERENCES

Casciotti, L., Ely, K. H., Williams, M. E. and Khan, I. A. (2002). CD8(+)-T-cell immunity against Toxoplasma gondii can be induced but not maintained in mice lacking conventional CD4(+) T cells. Infection and Immunity 70, 434–443.Google Scholar
Chuang, S. C., Ko, J. C., Chen, C. P., Du, J. T. and Yang, C. D. (2013 a). Encapsulation of chimeric protein rSAG1/2 into poly(lactide-co-glycolide) microparticles induces long-term protective immunity against Toxoplasma gondii in mice. Experimental Parasitology 134, 430–437. doi: 10.1016/j.exppara.2013.04.002.Google Scholar
Chuang, S. C., Ko, J. C., Chen, C. P., Du, J. T. and Yang, C. D. (2013 b). Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles. Parasites and Vectors 6, 34. doi: 10.1186/1756-3305-6-34.Google Scholar
Contini, C. (2008). Clinical and diagnostic management of toxoplasmosis in the immunocompromised patient. Parassitologia 50, 45–50.Google Scholar
Dubey, J. P. and Jones, J. L. (2008). Toxoplasma gondii infection in humans and animals in the United States. International Journal for Parasitology 38, 1257–1278. doi: 10.1016/j.ijpara.2008.03.007.Google Scholar
Dubey, J. P., Lago, E. G., Gennari, S. M., Su, C. and Jones, J. L. (2012). Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. Parasitology 139, 1375–1424. doi: 10.1017/S0031182012000765.Google Scholar
Fatoohi, A. F., Cozon, G. J., Greenland, T., Ferrandiz, J., Bienvenu, J., Picot, S. and Peyron, F. (2002). Cellular immune responses to recombinant antigens in pregnant women chronically infected with Toxoplasma gondii. Clinical and Diagnostic Laboratory Immunology 9, 704–707.Google ScholarPubMed
Garlapati, S., Facci, M., Polewicz, M., Strom, S., Babiuk, L. A., Mutwiri, G., Hancock, R. E., Elliott, M. R. and Gerdts, V. (2009). Strategies to link innate and adaptive immunity when designing vaccine adjuvants. Veterinary Immunology and Immunopathology 128, 184–191. doi: 10.1016/j.vetimm.2008.10.298.CrossRefGoogle ScholarPubMed
Ghaderi, R. and Carlfors, J. (1997). Biological activity of lysozyme after entrapment in poly(d,l-lactide-co-glycolide)-microspheres. Pharmaceutical Research 14, 1556–1562.Google Scholar
Grimwood, J. and Smith, J. E. (1996). Toxoplasma gondii: the role of parasite surface and secreted proteins in host cell invasion. International Journal for Parasitology 26, 169–173. doi: 0020-7519(95)00103-4.Google Scholar
Heegaard, P. M., Dedieu, L., Johnson, N., Le Potier, M. F., Mockey, M., Mutinelli, F., Vahlenkamp, T., Vascellari, M. and Sorensen, N. S. (2011). Adjuvants and delivery systems in veterinary vaccinology: current state and future developments. Archives of Virology 156, 183–202. doi: 10.1007/s00705-010-0863-1.Google Scholar
Innes, E. A., Bartley, P. M., Maley, S., Katzer, F. and Buxton, D. (2009). Veterinary vaccines against Toxoplasma gondii. Memorias do Instituto Oswaldo Cruz 104, 246–251. doi: S0074-02762009000200018.Google Scholar
Jain, S., O'Hagan, D. T. and Singh, M. (2011). The long-term potential of biodegradable poly(lactide-co-glycolide) microparticles as the next-generation vaccine adjuvant. Expert Review of Vaccines 10, 1731–1742. doi: 10.1586/erv.11.126.CrossRefGoogle ScholarPubMed
Jeffery, H., Davis, S. S. and O'Hagan, D. T. (1993). The preparation and characterization of poly(lactide-co-glycolide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in-water emulsion solvent evaporation technique. Pharmaceutical Research 10, 362–368.Google Scholar
Jongert, E., Roberts, C. W., Gargano, N., Forster-Waldl, E. and Petersen, E. (2009). Vaccines against Toxoplasma gondii: challenges and opportunities. Memorias do Instituto Oswaldo Cruz 104, 252–266.Google Scholar
Jongert, E., Lemiere, A., Van Ginderachter, J., De Craeye, S., Huygen, K. and D'Souza, S. (2010). Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute Toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine 28, 2556–2564. doi: 10.1016/j.vaccine.2010.01.031.CrossRefGoogle ScholarPubMed
Kavanagh, O. V., Earley, B., Murray, M., Foster, C. J. and Adair, B. M. (2003). Antigen-specific IgA and IgG responses in calves inoculated intranasally with ovalbumin encapsulated in poly(DL-lactide-co-glycolide) microspheres. Vaccine 21, 4472–4480.Google Scholar
Li, Z., Zhao, Z. J., Zhu, X. Q., Ren, Q. S., Nie, F. F., Gao, J. M., Gao, X. J., Yang, T. B., Zhou, W. L., Shen, J. L., Wang, Y., Lu, F. L., Chen, X. G., Hide, G., Ayala, F. J. and Lun, Z. R. (2012). Differences in iNOS and arginase expression and activity in the macrophages of rats are responsible for the resistance against T. gondii infection. PLOS ONE 7, e35834. doi: 10.1371/journal.pone.0035834.Google Scholar
Lim, T. Y., Poh, C. K. and Wang, W. (2009). Poly(lactic-co-glycolic acid) as a controlled release delivery device. Journal of Materials Science–Materials in Medicine 20, 1669–1675. doi: 10.1007/s10856-009-3727-z.Google Scholar
Machado, A. V., Caetano, B. C., Barbosa, R. P., Salgado, A. P., Rabelo, R. H., Garcia, C. C., Bruna-Romero, O., Escriou, N. and Gazzinelli, R. T. (2010). Prime and boost immunization with influenza and adenovirus encoding the Toxoplasma gondii surface antigen 2 (SAG2) induces strong protective immunity. Vaccine 28, 3247–3256. doi: 10.1016/j.vaccine.2010.02.003.Google Scholar
McLeod, R., Beem, M. O. and Estes, R. G. (1985). Lymphocyte anergy specific to Toxoplasma gondii antigens in a baby with congenital toxoplasmosis. Journal of Clinical and Laboratory Immunology 17, 149–153.Google Scholar
Men, Y., Audran, R., Thomasin, C., Eberl, G., Demotz, S., Merkle, H. P., Gander, B. and Corradin, G. (1999). MHC class I- and class II-restricted processing and presentation of microencapsulated antigens. Vaccine 17, 1047–1056.Google Scholar
Meng, M., He, S., Zhao, G., Bai, Y., Zhou, H., Cong, H., Lu, G., Zhao, Q. and Zhu, X. Q. (2012). Evaluation of protective immune responses induced by DNA vaccines encoding Toxoplasma gondii surface antigen 1 (SAG1) and 14-3-3 protein in BALB/c mice. Parasites and Vectors 5, 273. doi: 10.1186/1756-3305-5-273.Google Scholar
Mishima, M., Xuan, X., Shioda, A., Omata, Y., Fujisaki, K., Nagasawa, H. and Mikami, T. (2001). Modified protection against Toxoplasma gondii lethal infection and brain cyst formation by vaccination with SAG2 and SRS1. Journal of Veterinary Medical Science 63, 433–438.Google Scholar
Newman, K. D., Elamanchili, P., Kwon, G. S. and Samuel, J. (2002). Uptake of poly(D,L-lactic-co-glycolic acid) microspheres by antigen-presenting cells in vivo. Journal of Biomedical Materials Research 60, 480–486.Google Scholar
Rajendran, C., Su, C. and Dubey, J. P. (2012). Molecular genotyping of Toxoplasma gondii from Central and South America revealed high diversity within and between populations. Infection Genetics and Evolution 12, 359–368. doi: 10.1016/j.meegid.2011.12.010.Google Scholar
Singh, M. and O'Hagan, D. T. (2003). Recent advances in veterinary vaccine adjuvants. International Journal for Parasitology 33, 469–478. doi: S0020751903000535.Google Scholar
Sinha, V. R. and Trehan, A. (2003). Biodegradable microspheres for protein delivery. Journal of Controlled Release 90, 261–280.Google Scholar
Stanley, A. C., Buxton, D., Innes, E. A. and Huntley, J. F. (2004). Intranasal immunisation with Toxoplasma gondii tachyzoite antigen encapsulated into PLG microspheres induces humoral and cell-mediated immunity in sheep. Vaccine 22, 3929–3941. doi: 10.1016/j.vaccine.2004.04.022.Google Scholar
Sturesson, C. and Carlfors, J. (2000). Incorporation of protein in PLG-microspheres with retention of bioactivity. Journal of Controlled Release 67, 171–178. doi: S0168365900002054.Google Scholar
Subauste, C. S. and Remington, J. S. (1993). Immunity to Toxoplasma gondii. Current Opinion in Immunology 5, 532–537.Google Scholar
Uchida, M., Natsume, H., Kishino, T., Seki, T., Ogihara, M., Juni, K., Kimura, M. and Morimoto, Y. (2006). Immunization by particle bombardment of antigen-loaded poly-(DL-lactide-co-glycolide) microspheres in mice. Vaccine 24, 2120–2130. doi: 10.1016/j.vaccine.2005.11.027.Google Scholar
Yang, C. D., Chang, G. N. and Chao, D. (2003). Protective immunity against Toxoplasma gondii in mice induced by the SAG2 internal image of anti-idiotype antibody. Parasitology Research 91, 452–457. doi: 10.1007/s00436-003-1006-3.Google Scholar
Yang, C. D., Chang, G. N. and Chao, D. (2004). Protective immunity against Toxoplasma gondii in mice induced by a chimeric protein rSAG1/2. Parasitology Research 92, 58–64. doi: 10.1007/s00436-003-0992-5.Google Scholar