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A Toxoplasma gondii vaccine encoding multistage antigens in conjunction with ubiquitin confers protective immunity to BALB/c mice against parasite infection.

Yin H, Zhao L, Wang T, Zhou H, He S, Cong H - Parasit Vectors (2015)

Bottom Line: DNA vaccines have proved effective in the protection against parasites.Our results indicated that the DNA vaccine had the advantage of inducing a stronger humoral response, whereas the adenovirus-vectored vaccine effectively improved the cellular immune response.Priming vaccination with DNA vaccine and boosting with the recombinant adenovirus vaccine encoding ubiquitin conjugated multi-stage antigens of T. gondii was proved to be a potential strategy against the infection of type I and type II parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Parasitology, Shandong University, School of Medicine, No. 44 Wenhuaxi Road, Jinan, Shandong, 250012, PR China. yinhuiquan521@126.com.

ABSTRACT

Background: Toxoplasma gondii is a widely prevalent intracellular parasite which infects almost all warm-blooded animals including humans and causes serious zoonotic toxoplasmosis. DNA vaccines have proved effective in the protection against parasites. However, the problems of weak immunity and inefficient delivery of DNA vaccine remain major issues. Therefore, comprehensive antigens derived from all stages of the parasite, effective adjuvants and delivery systems should be considered in the vaccine construction.

Methods: SAG3101-144,ROP18347-396, MIC6288-347, GRA7182-224, MAG158-125, BAG1156-211 and SPA142-200, derived from antigens in tachyzoite, bradyzoite and sporozoite stages of T. gondii were screened based on CD8(+) T cell epitope binding affinity to HLA and H-2. We constructed a recombinant DNA vaccine and an adenovirus vaccine encoding multi-stage antigen of T. gondii linked to ubiquitin molecules and vaccinated BALB/c mice with different strategies. Antibodies, cytokines, splenocytes proliferation, as well as the percentage of CD4(+) and CD8(+) T cells in immunized mouse were analyzed by the Enzyme-Linked Immunosorbent Assays (ELISA), Flow Cytometry (FCM). Protective efficacy was evaluated by challenging immunized mice with type I and type II parasite.

Results: Our results indicated that the DNA vaccine had the advantage of inducing a stronger humoral response, whereas the adenovirus-vectored vaccine effectively improved the cellular immune response. Priming with DNA vaccine and boosting with adenovirus-vectored vaccine induced Th1-type immune responses with highest levels of IgG2a and secretion of cytokines IL-2 and IFN-γ. Effective protection against type I and type II parasite with an increase in survival rate and a decrease in brain cyst burden was achieved in immunized mice.

Conclusions: Priming vaccination with DNA vaccine and boosting with the recombinant adenovirus vaccine encoding ubiquitin conjugated multi-stage antigens of T. gondii was proved to be a potential strategy against the infection of type I and type II parasite.

No MeSH data available.


Related in: MedlinePlus

Adenovirus-vectored vaccine enhanced the cellular immune response in BALB/c mice. Ad-UMAS constructed using an adenovirus vector expressing the ubiquitin-conjugated MAS genes. The production levels of antibodies (IgG, IgG1 and IgG2a) (a), cytokines (IL-2, IL-10 and IFN-γ) (b), and splenocytes proliferation (c) were detected same as Fig. 2. *indicates statistically significant differences between Ad-UMAS vaccinated mice and p-UMAS vaccinated mice
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Fig4: Adenovirus-vectored vaccine enhanced the cellular immune response in BALB/c mice. Ad-UMAS constructed using an adenovirus vector expressing the ubiquitin-conjugated MAS genes. The production levels of antibodies (IgG, IgG1 and IgG2a) (a), cytokines (IL-2, IL-10 and IFN-γ) (b), and splenocytes proliferation (c) were detected same as Fig. 2. *indicates statistically significant differences between Ad-UMAS vaccinated mice and p-UMAS vaccinated mice

Mentions: The recombinant adenovirus vaccine (Ad-UMAS) was constructed using an adenovirus vector (pHBAd) expressing the ubiquitin-conjugated MAS genes. As shown in Fig. 4, compared with the p-UMAS DNA vaccination group, the levels of IgG, IgG2a in the serum of Ad-UMAS immunized mice was lower, however, significant higher levels of IFN-γ (1478 ± 51.8 pg/mL) and IL-2 (489 ± 11.5 pg/mL) production and enhanced splenocyte proliferation were achieved in the Ad-UMAS vaccine group (P <0.05). Notably, the percentages of CD8+ T cells in the splenocytes of Ad-UMAS vaccinated mice were significantly augmented compared with p-UMAS vaccinated mice (P <0.05) (Fig. 3).Fig. 4


A Toxoplasma gondii vaccine encoding multistage antigens in conjunction with ubiquitin confers protective immunity to BALB/c mice against parasite infection.

Yin H, Zhao L, Wang T, Zhou H, He S, Cong H - Parasit Vectors (2015)

Adenovirus-vectored vaccine enhanced the cellular immune response in BALB/c mice. Ad-UMAS constructed using an adenovirus vector expressing the ubiquitin-conjugated MAS genes. The production levels of antibodies (IgG, IgG1 and IgG2a) (a), cytokines (IL-2, IL-10 and IFN-γ) (b), and splenocytes proliferation (c) were detected same as Fig. 2. *indicates statistically significant differences between Ad-UMAS vaccinated mice and p-UMAS vaccinated mice
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4588682&req=5

Fig4: Adenovirus-vectored vaccine enhanced the cellular immune response in BALB/c mice. Ad-UMAS constructed using an adenovirus vector expressing the ubiquitin-conjugated MAS genes. The production levels of antibodies (IgG, IgG1 and IgG2a) (a), cytokines (IL-2, IL-10 and IFN-γ) (b), and splenocytes proliferation (c) were detected same as Fig. 2. *indicates statistically significant differences between Ad-UMAS vaccinated mice and p-UMAS vaccinated mice
Mentions: The recombinant adenovirus vaccine (Ad-UMAS) was constructed using an adenovirus vector (pHBAd) expressing the ubiquitin-conjugated MAS genes. As shown in Fig. 4, compared with the p-UMAS DNA vaccination group, the levels of IgG, IgG2a in the serum of Ad-UMAS immunized mice was lower, however, significant higher levels of IFN-γ (1478 ± 51.8 pg/mL) and IL-2 (489 ± 11.5 pg/mL) production and enhanced splenocyte proliferation were achieved in the Ad-UMAS vaccine group (P <0.05). Notably, the percentages of CD8+ T cells in the splenocytes of Ad-UMAS vaccinated mice were significantly augmented compared with p-UMAS vaccinated mice (P <0.05) (Fig. 3).Fig. 4

Bottom Line: DNA vaccines have proved effective in the protection against parasites.Our results indicated that the DNA vaccine had the advantage of inducing a stronger humoral response, whereas the adenovirus-vectored vaccine effectively improved the cellular immune response.Priming vaccination with DNA vaccine and boosting with the recombinant adenovirus vaccine encoding ubiquitin conjugated multi-stage antigens of T. gondii was proved to be a potential strategy against the infection of type I and type II parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Parasitology, Shandong University, School of Medicine, No. 44 Wenhuaxi Road, Jinan, Shandong, 250012, PR China. yinhuiquan521@126.com.

ABSTRACT

Background: Toxoplasma gondii is a widely prevalent intracellular parasite which infects almost all warm-blooded animals including humans and causes serious zoonotic toxoplasmosis. DNA vaccines have proved effective in the protection against parasites. However, the problems of weak immunity and inefficient delivery of DNA vaccine remain major issues. Therefore, comprehensive antigens derived from all stages of the parasite, effective adjuvants and delivery systems should be considered in the vaccine construction.

Methods: SAG3101-144,ROP18347-396, MIC6288-347, GRA7182-224, MAG158-125, BAG1156-211 and SPA142-200, derived from antigens in tachyzoite, bradyzoite and sporozoite stages of T. gondii were screened based on CD8(+) T cell epitope binding affinity to HLA and H-2. We constructed a recombinant DNA vaccine and an adenovirus vaccine encoding multi-stage antigen of T. gondii linked to ubiquitin molecules and vaccinated BALB/c mice with different strategies. Antibodies, cytokines, splenocytes proliferation, as well as the percentage of CD4(+) and CD8(+) T cells in immunized mouse were analyzed by the Enzyme-Linked Immunosorbent Assays (ELISA), Flow Cytometry (FCM). Protective efficacy was evaluated by challenging immunized mice with type I and type II parasite.

Results: Our results indicated that the DNA vaccine had the advantage of inducing a stronger humoral response, whereas the adenovirus-vectored vaccine effectively improved the cellular immune response. Priming with DNA vaccine and boosting with adenovirus-vectored vaccine induced Th1-type immune responses with highest levels of IgG2a and secretion of cytokines IL-2 and IFN-γ. Effective protection against type I and type II parasite with an increase in survival rate and a decrease in brain cyst burden was achieved in immunized mice.

Conclusions: Priming vaccination with DNA vaccine and boosting with the recombinant adenovirus vaccine encoding ubiquitin conjugated multi-stage antigens of T. gondii was proved to be a potential strategy against the infection of type I and type II parasite.

No MeSH data available.


Related in: MedlinePlus