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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.

Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ - BMC Infect. Dis. (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.

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.

No MeSH data available.


Related in: MedlinePlus

IgG antibodies induced by various protein vaccines in the sera of mice at 0, 2, and 8 weeks. Each bar represents the mean OD (± SE, n = 3). *P < 0.05, **P < 0.01 compared with the controls. NS: not significant
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Fig2: IgG antibodies induced by various protein vaccines in the sera of mice at 0, 2, and 8 weeks. Each bar represents the mean OD (± SE, n = 3). *P < 0.05, **P < 0.01 compared with the controls. NS: not significant

Mentions: Three serum samples from each vaccinated mouse group were collected at 0, 2, and 8 weeks to detect specific IgG antibodies. All the protein vaccines elicited specific humoral responses and the levels of IgG antibodies in the experimental mice increased sequentially with successive immunizations with the tested antigens, and reached their highest levels in week 8 (Fig. 2). However, no significant differences in the antibody levels were detected between pre- and post-immunization in the control groups. Six weeks after the last vaccination, the levels of IgG antibodies in the mice immunized with rROP18 + PLG or rCDPK6 + rROP18 + PLG were significantly higher than those in the mice immunized with rROP18 or rCDPK6 + rROP18 (P < 0.01), but were not statistically different from those in the mice immunized with various proteins + 206 adjuvant (P > 0.05) (Fig. 2).Fig. 2


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.

Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ - BMC Infect. Dis. (2016)

IgG antibodies induced by various protein vaccines in the sera of mice at 0, 2, and 8 weeks. Each bar represents the mean OD (± SE, n = 3). *P < 0.05, **P < 0.01 compared with the controls. NS: not significant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836102&req=5

Fig2: IgG antibodies induced by various protein vaccines in the sera of mice at 0, 2, and 8 weeks. Each bar represents the mean OD (± SE, n = 3). *P < 0.05, **P < 0.01 compared with the controls. NS: not significant
Mentions: Three serum samples from each vaccinated mouse group were collected at 0, 2, and 8 weeks to detect specific IgG antibodies. All the protein vaccines elicited specific humoral responses and the levels of IgG antibodies in the experimental mice increased sequentially with successive immunizations with the tested antigens, and reached their highest levels in week 8 (Fig. 2). However, no significant differences in the antibody levels were detected between pre- and post-immunization in the control groups. Six weeks after the last vaccination, the levels of IgG antibodies in the mice immunized with rROP18 + PLG or rCDPK6 + rROP18 + PLG were significantly higher than those in the mice immunized with rROP18 or rCDPK6 + rROP18 (P < 0.01), but were not statistically different from those in the mice immunized with various proteins + 206 adjuvant (P > 0.05) (Fig. 2).Fig. 2

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.

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.

No MeSH data available.


Related in: MedlinePlus