TY - JOUR
T1 - Fabrication of nanoadjuvant with poly-σ- caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity
AU - Prashant, Chandravilas Keshvan
AU - Bhat, Madhusudan
AU - Srivastava Kumar, Sandeep
AU - Saxena, Ankit
AU - Kumar, Manoj
AU - Singh, Amar
AU - Samim, Mohammed
AU - Ahmad, Farhan Jalees
AU - Dinda, Amit Kumar
PY - 2014/2/12
Y1 - 2014/2/12
N2 - Purpose: The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-σ- 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.
AB - Purpose: The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-σ- 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.
KW - Adjuvant
KW - Antigen cross-presentation
KW - Poly-σ-caprolactone nanoparticles
KW - Tetanus toxoid
KW - Vaccine
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U2 - 10.2147/IJN.S55892
DO - 10.2147/IJN.S55892
M3 - Article
C2 - 24611010
AN - SCOPUS:84896853132
SN - 1176-9114
VL - 9
SP - 937
EP - 950
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
IS - 1
M1 - 937
ER -