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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.

Chuang SC, Ko JC, Chen CP, Du JT, Yang CD - Parasit Vectors (2013)

Bottom Line: We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)).PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection.Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, No 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.

ABSTRACT

Background: Current development efforts of subunit vaccines against Toxoplasma gondii, the etiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigen 1 (SAG1). Since microparticles made from poly (lactide-co-glycolide) (PLG) polymers have been developed as safe, potent adjuvants or delivery systems, we aimed to encapsulate recombinant SAG1 (rSAG1) with the PLG polymers to prepare PLG-encapsulated rSAG1 (PLG-rSAG1) microparticles that would sustain rSAG1 release and generate long-lasting protective immunity against T. gondii in BALB/c mice.

Methods: In the present study, rSAG1 was encapsulated into PLG microparticles by the double emulsion method. PLG-rSAG1 microparticles were then intraperitoneally injected twice at a 14-day interval into BALB/c mice. We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)). Eight weeks after the last immunization, protective activities were also evaluated after a lethal subcutaneous challenge of 1 x 10(4) live T. gondii tachyzoites.

Results: PLG-rSAG1 microparticles, 4.25~6.58 micrometers in diameter, showed 69%~81% entrapment efficiency. The amount of released rSAG1 protein from microparticles increased gradually over a 35-day period and the protein still retained native SAG1 antigenicity. Intraperitoneal vaccination of mice with the microparticles resulted in enhanced SAG1-specific IgG titers as well as lymphocyte proliferation and, more importantly, these enhanced activities were maintained for 10 weeks. In addition, eight weeks after the last immunization, maximum production of gamma interferon was detected in mice immunized with PLG-rSAG1 microparticles. Furthermore, 80% (8/10) of mice immunized with PLG-rSAG1 microparticles survived at least 28 days after a lethal subcutaneous tachyzoite challenge.

Conclusions: Encapsulation of rSAG1 into PLG microparticles preserves the native SAG1 antigenicity and sustains the release of rSAG1 from microparticles. PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection. Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.

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Survival of immunized mice after a lethal tachyzoite challenge. Groups of mice were intraperitoneally immunized twice with PLG-rSAG1 microparticles (■ ), rSAG1 (Vet L-10) (● ), soluble rSAG1 alone (□ ), PLG (◊ ), or PBS (○ ). Eight weeks after boosting, five groups of 10 mice each were subcutaneously infected with 1×104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the final survival rates were calculated. *P<0.05 when comparing the PLG-rSAG1 group to the rSAG1 (Vet L-10) group.
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Figure 8: Survival of immunized mice after a lethal tachyzoite challenge. Groups of mice were intraperitoneally immunized twice with PLG-rSAG1 microparticles (■ ), rSAG1 (Vet L-10) (● ), soluble rSAG1 alone (□ ), PLG (◊ ), or PBS (○ ). Eight weeks after boosting, five groups of 10 mice each were subcutaneously infected with 1×104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the final survival rates were calculated. *P<0.05 when comparing the PLG-rSAG1 group to the rSAG1 (Vet L-10) group.

Mentions: We then determined whether PLG-rSAG1 microparticles could confer effective protection in mice. Eight weeks after boosting (the 10th week), all groups of 10 mice each were subcutaneously challenged with 1 × 104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the survival rates were recorded (Figure8). All mice administrated with soluble rSAG1 alone, PLG or PBS died within 8 days after challenge and displayed no protection against the challenge. Two out of 10 mice immunized with rSAG1 (Vet L-10) survived during the challenge study and showed a low protection of 20%. However, only 2 mice died on the 21st day after challenge in the PLG-rSAG1-immunized group with the highest survival rate obtained in this group as 80%, which was significantly higher (P<0.05, chi-square test) than that of the rSAG1 (Vet L-10) group. Therefore, vaccination with rSAG1 encapsulated with the PLG polymers provided a substantial resistance to the experimental challenge of T. gondii tachyzoites.


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.

Chuang SC, Ko JC, Chen CP, Du JT, Yang CD - Parasit Vectors (2013)

Survival of immunized mice after a lethal tachyzoite challenge. Groups of mice were intraperitoneally immunized twice with PLG-rSAG1 microparticles (■ ), rSAG1 (Vet L-10) (● ), soluble rSAG1 alone (□ ), PLG (◊ ), or PBS (○ ). Eight weeks after boosting, five groups of 10 mice each were subcutaneously infected with 1×104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the final survival rates were calculated. *P<0.05 when comparing the PLG-rSAG1 group to the rSAG1 (Vet L-10) group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584932&req=5

Figure 8: Survival of immunized mice after a lethal tachyzoite challenge. Groups of mice were intraperitoneally immunized twice with PLG-rSAG1 microparticles (■ ), rSAG1 (Vet L-10) (● ), soluble rSAG1 alone (□ ), PLG (◊ ), or PBS (○ ). Eight weeks after boosting, five groups of 10 mice each were subcutaneously infected with 1×104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the final survival rates were calculated. *P<0.05 when comparing the PLG-rSAG1 group to the rSAG1 (Vet L-10) group.
Mentions: We then determined whether PLG-rSAG1 microparticles could confer effective protection in mice. Eight weeks after boosting (the 10th week), all groups of 10 mice each were subcutaneously challenged with 1 × 104 live tachyzoites of T. gondii (RH strain). Animals were observed daily for an additional month (28 days) and the survival rates were recorded (Figure8). All mice administrated with soluble rSAG1 alone, PLG or PBS died within 8 days after challenge and displayed no protection against the challenge. Two out of 10 mice immunized with rSAG1 (Vet L-10) survived during the challenge study and showed a low protection of 20%. However, only 2 mice died on the 21st day after challenge in the PLG-rSAG1-immunized group with the highest survival rate obtained in this group as 80%, which was significantly higher (P<0.05, chi-square test) than that of the rSAG1 (Vet L-10) group. Therefore, vaccination with rSAG1 encapsulated with the PLG polymers provided a substantial resistance to the experimental challenge of T. gondii tachyzoites.

Bottom Line: We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)).PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection.Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, No 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.

ABSTRACT

Background: Current development efforts of subunit vaccines against Toxoplasma gondii, the etiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigen 1 (SAG1). Since microparticles made from poly (lactide-co-glycolide) (PLG) polymers have been developed as safe, potent adjuvants or delivery systems, we aimed to encapsulate recombinant SAG1 (rSAG1) with the PLG polymers to prepare PLG-encapsulated rSAG1 (PLG-rSAG1) microparticles that would sustain rSAG1 release and generate long-lasting protective immunity against T. gondii in BALB/c mice.

Methods: In the present study, rSAG1 was encapsulated into PLG microparticles by the double emulsion method. PLG-rSAG1 microparticles were then intraperitoneally injected twice at a 14-day interval into BALB/c mice. We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)). Eight weeks after the last immunization, protective activities were also evaluated after a lethal subcutaneous challenge of 1 x 10(4) live T. gondii tachyzoites.

Results: PLG-rSAG1 microparticles, 4.25~6.58 micrometers in diameter, showed 69%~81% entrapment efficiency. The amount of released rSAG1 protein from microparticles increased gradually over a 35-day period and the protein still retained native SAG1 antigenicity. Intraperitoneal vaccination of mice with the microparticles resulted in enhanced SAG1-specific IgG titers as well as lymphocyte proliferation and, more importantly, these enhanced activities were maintained for 10 weeks. In addition, eight weeks after the last immunization, maximum production of gamma interferon was detected in mice immunized with PLG-rSAG1 microparticles. Furthermore, 80% (8/10) of mice immunized with PLG-rSAG1 microparticles survived at least 28 days after a lethal subcutaneous tachyzoite challenge.

Conclusions: Encapsulation of rSAG1 into PLG microparticles preserves the native SAG1 antigenicity and sustains the release of rSAG1 from microparticles. PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection. Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.

Show MeSH
Related in: MedlinePlus