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Fabrication of nanoadjuvant with poly-ε-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity.

Prashant CK, Bhat M, Srivastava SK, Saxena A, Kumar M, Singh A, Samim M, Ahmad FJ, Dinda AK - Int J Nanomedicine (2014)

Bottom Line: They did not elicit efficient CD8(+) T-cell responses.This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses.The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.

ABSTRACT

Purpose: The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-ε-caprolactone nanoparticles (PCL NPs) of two size ranges, ie, mean 61.2 nm (small) and 467.6 nm (large), and study its effect on macrophage polarization as well as antigen presentation in human monocyte-derived macrophages in vitro, along with humoral and cell-mediated immune (CMI) response generated in Swiss albino mice following immunization with the TT-loaded NPs.

Materials and methods: PCL NPs were synthesized by solvent evaporation. The antigen-loaded PCL NPs were characterized for size, zeta potential, and protein-release kinetics. Swiss albino mice were immunized with the antigen-loaded PCL NPs. Flow cytometry was used to quantify interferon-γ- and interleukin-4-secreting cluster of differentiation (CD)4(+) and CD8(+) T cells in the spleen, and enzyme-linked immunosorbent assay was used to quantify anti-TT antibody levels in the serum of immunized mice.

Results: Small PCL NPs generated an M1/M2 type polarization of human blood monocyte-derived macrophages and T helper (Th)1/Th2 polarization of autologous CD4(+) T cells. Efficient CD8(+) T-cell responses were also elicited. Large PCL NPs failed to cause any type of macrophage polarization. They did not elicit efficient CD8(+) T-cell responses.

Conclusion: TT-loaded small PCL NPs were able to generate persistent and strong CMI and humoral responses against TT 2 months after single injection in mice without booster dose. This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses. The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.

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Related in: MedlinePlus

Rhodamine B-labeled small poly-ε-caprolactone nanoparticles draining into inguinal lymph nodes after 7 days of intramuscular injection in thighs of mice. Magnification 200×.
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f9-ijn-9-937: Rhodamine B-labeled small poly-ε-caprolactone nanoparticles draining into inguinal lymph nodes after 7 days of intramuscular injection in thighs of mice. Magnification 200×.

Mentions: Rhodamine B-labeled small PCL NPs injected IM in the thighs of mice were found to drain into the inguinal lymph nodes after 3 and 7 days of injection (Figure 9). Immunofluorescence staining done on lymph-node sections isolated from mice immunized with TT-loaded non-rhodamine B-labeled small PCL NPs showed that CD8+ T cells produced significantly more IFN-γ and IL-4 after 2 months of immunization compared to the negative control (Figure 10).


Fabrication of nanoadjuvant with poly-ε-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity.

Prashant CK, Bhat M, Srivastava SK, Saxena A, Kumar M, Singh A, Samim M, Ahmad FJ, Dinda AK - Int J Nanomedicine (2014)

Rhodamine B-labeled small poly-ε-caprolactone nanoparticles draining into inguinal lymph nodes after 7 days of intramuscular injection in thighs of mice. Magnification 200×.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928464&req=5

f9-ijn-9-937: Rhodamine B-labeled small poly-ε-caprolactone nanoparticles draining into inguinal lymph nodes after 7 days of intramuscular injection in thighs of mice. Magnification 200×.
Mentions: Rhodamine B-labeled small PCL NPs injected IM in the thighs of mice were found to drain into the inguinal lymph nodes after 3 and 7 days of injection (Figure 9). Immunofluorescence staining done on lymph-node sections isolated from mice immunized with TT-loaded non-rhodamine B-labeled small PCL NPs showed that CD8+ T cells produced significantly more IFN-γ and IL-4 after 2 months of immunization compared to the negative control (Figure 10).

Bottom Line: They did not elicit efficient CD8(+) T-cell responses.This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses.The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.

ABSTRACT

Purpose: The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-ε-caprolactone nanoparticles (PCL NPs) of two size ranges, ie, mean 61.2 nm (small) and 467.6 nm (large), and study its effect on macrophage polarization as well as antigen presentation in human monocyte-derived macrophages in vitro, along with humoral and cell-mediated immune (CMI) response generated in Swiss albino mice following immunization with the TT-loaded NPs.

Materials and methods: PCL NPs were synthesized by solvent evaporation. The antigen-loaded PCL NPs were characterized for size, zeta potential, and protein-release kinetics. Swiss albino mice were immunized with the antigen-loaded PCL NPs. Flow cytometry was used to quantify interferon-γ- and interleukin-4-secreting cluster of differentiation (CD)4(+) and CD8(+) T cells in the spleen, and enzyme-linked immunosorbent assay was used to quantify anti-TT antibody levels in the serum of immunized mice.

Results: Small PCL NPs generated an M1/M2 type polarization of human blood monocyte-derived macrophages and T helper (Th)1/Th2 polarization of autologous CD4(+) T cells. Efficient CD8(+) T-cell responses were also elicited. Large PCL NPs failed to cause any type of macrophage polarization. They did not elicit efficient CD8(+) T-cell responses.

Conclusion: TT-loaded small PCL NPs were able to generate persistent and strong CMI and humoral responses against TT 2 months after single injection in mice without booster dose. This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses. The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.

Show MeSH
Related in: MedlinePlus