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Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice.
BMC Infect Dis. 2016 Apr 18; 16:168.BI

Abstract

BACKGROUND

Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. However, no effective vaccine is yet available. Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers.

METHODS

Two recombinant proteins, rCDPK6 and rROP18, were encapsulated in poly(D,L-lactide-co-glycolide) (PLG), and then injected subcutaneously into Kunming mice. The mice immune responses were evaluated in terms of lympho-proliferation, cytokine expression, and antibodies. The survival of infected mice and brain cyst formation were also evaluated at 6 weeks after challenge with T. gondii RH strain (genotype I) or PRU strain (genotype II).

RESULTS

Both protein vaccines induced Th1-biased immune responses, with increased specific antibodies and T cells, high levels of interferon-γ and interleukin 2, and strong lymphocyte proliferative responses. The mice immunized with the various protein vaccines survived slightly longer time than the control groups (P > 0.05) after injection with T. gondii RH strain. There were fewer brain cysts in the mice in all the immunized groups than that in the control groups, and the brain cysts were significantly reduced in mice immunized with proteins + 206, rCDPK6 + PLG and rCDPK6 + rROP18 + PLG (P < 0.05) compared controls. Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.

CONCLUSIONS

These findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis.

Authors+Show Affiliations

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China. Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China.State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China. Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University College of Veterinary Medicine, Yangzhou, Jiangsu Province, 225009, PR China.College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, PR China.State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China. zhuxingquan@caas.cn. Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University College of Veterinary Medicine, Yangzhou, Jiangsu Province, 225009, PR China. zhuxingquan@caas.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27090890

Citation

Zhang, Nian-Zhang, et al. "Vaccination With Toxoplasma Gondii Calcium-dependent Protein Kinase 6 and Rhoptry Protein 18 Encapsulated in Poly(lactide-co-glycolide) Microspheres Induces Long-term Protective Immunity in Mice." BMC Infectious Diseases, vol. 16, 2016, p. 168.
Zhang NZ, Xu Y, Wang M, et al. Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infect Dis. 2016;16:168.
Zhang, N. Z., Xu, Y., Wang, M., Chen, J., Huang, S. Y., Gao, Q., & Zhu, X. Q. (2016). Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice. BMC Infectious Diseases, 16, 168. https://doi.org/10.1186/s12879-016-1496-0
Zhang NZ, et al. Vaccination With Toxoplasma Gondii Calcium-dependent Protein Kinase 6 and Rhoptry Protein 18 Encapsulated in Poly(lactide-co-glycolide) Microspheres Induces Long-term Protective Immunity in Mice. BMC Infect Dis. 2016 Apr 18;16:168. PubMed PMID: 27090890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice. AU - Zhang,Nian-Zhang, AU - Xu,Ying, AU - Wang,Meng, AU - Chen,Jia, AU - Huang,Si-Yang, AU - Gao,Qi, AU - Zhu,Xing-Quan, Y1 - 2016/04/18/ PY - 2015/05/24/received PY - 2016/04/06/accepted PY - 2016/4/20/entrez PY - 2016/4/20/pubmed PY - 2016/11/10/medline KW - Calcium-dependent protein kinase 6 KW - PLG microparticles KW - Protein vaccine KW - Rhoptry protein 18 KW - Toxoplasma gondii KW - Toxoplasmosis SP - 168 EP - 168 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 16 N2 - BACKGROUND: Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. However, no effective vaccine is yet available. Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers. METHODS: Two recombinant proteins, rCDPK6 and rROP18, were encapsulated in poly(D,L-lactide-co-glycolide) (PLG), and then injected subcutaneously into Kunming mice. The mice immune responses were evaluated in terms of lympho-proliferation, cytokine expression, and antibodies. The survival of infected mice and brain cyst formation were also evaluated at 6 weeks after challenge with T. gondii RH strain (genotype I) or PRU strain (genotype II). RESULTS: Both protein vaccines induced Th1-biased immune responses, with increased specific antibodies and T cells, high levels of interferon-γ and interleukin 2, and strong lymphocyte proliferative responses. The mice immunized with the various protein vaccines survived slightly longer time than the control groups (P > 0.05) after injection with T. gondii RH strain. There were fewer brain cysts in the mice in all the immunized groups than that in the control groups, and the brain cysts were significantly reduced in mice immunized with proteins + 206, rCDPK6 + PLG and rCDPK6 + rROP18 + PLG (P < 0.05) compared controls. Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge. CONCLUSIONS: These findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/27090890/Vaccination_with_Toxoplasma_gondii_calcium_dependent_protein_kinase_6_and_rhoptry_protein_18_encapsulated_in_poly_lactide_co_glycolide__microspheres_induces_long_term_protective_immunity_in_mice_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1496-0 DB - PRIME DP - Unbound Medicine ER -