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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

Immune response induced in mice via different vaccination strategies. Mice were vaccinated with the DNA/DNA (p-UMAS plasmid) or AdV/AdV (Ad-UMAS virus) or DNA/AdV (p-UMAS prime, Ad-UMAS boost) or AdV/DNA (Ad-UMAS prime, p-UMAS boost). 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 the marked group
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Fig5: Immune response induced in mice via different vaccination strategies. Mice were vaccinated with the DNA/DNA (p-UMAS plasmid) or AdV/AdV (Ad-UMAS virus) or DNA/AdV (p-UMAS prime, Ad-UMAS boost) or AdV/DNA (Ad-UMAS prime, p-UMAS boost). 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 the marked group

Mentions: As shown in Fig. 5, highest levels of humoral antibodies and cellular immune responses were achieved in mice immunization priming with the DNA vaccine and boosting with the Ad-UMAS vaccine. Compared with p-UMAS or Ad-UMAS immunization alone, higher levels of a specific IgG (predominance of IgG2a) and higher levels of cytokines (IFN-γ, 1691 ± 35.18 pg/mL and IL-2, 561 ± 19.68 pg/mL) were obtained by priming with p-UMAS and boosting with Ad-UMAS (P <0.05). When specific CD8+ T cell responses for peptides were determined by lymphocyte proliferation activity, priming with p-UMAS and boosting with Ad-UMAS showed the most potent proliferation activity compared with the other immunization strategy (P <0.05). However, there was no obvious enhanced immune response when mice received priming with Ad-UMAS and boosting with p-UMAS.Fig. 5


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)

Immune response induced in mice via different vaccination strategies. Mice were vaccinated with the DNA/DNA (p-UMAS plasmid) or AdV/AdV (Ad-UMAS virus) or DNA/AdV (p-UMAS prime, Ad-UMAS boost) or AdV/DNA (Ad-UMAS prime, p-UMAS boost). 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 the marked group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Immune response induced in mice via different vaccination strategies. Mice were vaccinated with the DNA/DNA (p-UMAS plasmid) or AdV/AdV (Ad-UMAS virus) or DNA/AdV (p-UMAS prime, Ad-UMAS boost) or AdV/DNA (Ad-UMAS prime, p-UMAS boost). 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 the marked group
Mentions: As shown in Fig. 5, highest levels of humoral antibodies and cellular immune responses were achieved in mice immunization priming with the DNA vaccine and boosting with the Ad-UMAS vaccine. Compared with p-UMAS or Ad-UMAS immunization alone, higher levels of a specific IgG (predominance of IgG2a) and higher levels of cytokines (IFN-γ, 1691 ± 35.18 pg/mL and IL-2, 561 ± 19.68 pg/mL) were obtained by priming with p-UMAS and boosting with Ad-UMAS (P <0.05). When specific CD8+ T cell responses for peptides were determined by lymphocyte proliferation activity, priming with p-UMAS and boosting with Ad-UMAS showed the most potent proliferation activity compared with the other immunization strategy (P <0.05). However, there was no obvious enhanced immune response when mice received priming with Ad-UMAS and boosting with p-UMAS.Fig. 5

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