The effects of salt on the physicochemical properties and immunogenicity of protein based vaccine formulated in cationic liposome

Recently, we have developed a simple and potent therapeutic cancer vaccine consisting of a cationic lipid and a peptide antigen. In this report, we expanded the utility of this formulation to a protein based vaccine. First, we formulated the human papillomavirus (HPV) 16 E7 protein (E7) in different doses of DOTAP liposome. The results showed that these formulations failed to regress an established tumor. However, when sodium chloride (30 mM) was added to the DOTAP (100 nmol) / E7 (20 μg) formulation, anti-tumor activity was generated in the immunized mice. Correlatively, 30 mM NaCl in the DOTAP/E7 protein formulation increased the particle size from ∼350 to 550 nm, decreased the protein loading capacity (from 95 to 90%), and finally increased the zeta potential (from 29 mV to 38 mV). Next, a model protein antigen ovalbumin (OVA) was formulated in different doses of DOTAP liposomes. Similarly, the results showed that 20 μg OVA formulated in 200 nmol DOTAP with 30 mM NaCl had the best OVA- specific antibody response, including both IgG1 and IgG2a, suggesting both Th1 and Th2 immune responses were generated by this formulation. In conclusion, we have expanded the application of cationic DOTAP liposome formulation to protein based vaccines and also identified that small amounts of salt could change the physicochemical properties of the vaccine formulation and enhance the activity of the DOTAP/protein based vaccine. The enhancement of immune responses by salt is possibly due to its interference of the electrostatic interaction between the cationic lipid and the protein antigen to facilitate the antigen release from the carrier and at the same time activate the antigen presenting cells

Pengaruh Konsentrasi Ekstrak Daun Kepel (Stelechocarpus Burahol (Bl) Hook F. & Th.) Terhadap Aktivitas Antioksidan Dan Sifat Fisik Sediaan Krim

This research was aimed to determine the effect of concentrations of Kepel leaves\u27 (Stelechocarpus burahol (BL) Hook f. & Th.)extract to antioxidant activity and physical properties of cream. Kepel leaves\u27 extract were made by infundation method. The antioxidant activity was tested by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. Cream was made in three formulas with variation concentrations of Kepel leaves\u27 extract (2,5; 5,0; 7,5%b/b) using w/o basis. Physical stability parameters tested in this research were homogenity, dispersive power, adhesion, and viscosity. Data were then analyzed statistically by ANOVA One Way and Turkey Test at 95% level of significance. The results showed that concentration of Kepel leaves\u27 extract as an active ingredient cause different color, odor, and viscosity of the cream. The concentrationdifference of Kepel Leaves\u27 extract as an active ingredient was not affected the homogenity, adhesion, and the separation ratio of the cream. The difference concentration was not cause affected daya sebar cream unless the formula II (5.0% w/w) and formula III (7.5% w/w). Increasing concentration of Kepel leaves\u27 extract caused a different antioxidant activity unless the formula II (5.0% w/w) and formula III (7.5% w/w)

Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the human immunodeficiency virus (HIV) his-tagged Tat (his-Tat) protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by subcutaneous injection with his-Tat/Ni-NP formulation (1.5 μg his-Tat/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific immunoglobulin G titer with his-Tat/Ni-NPs was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP-immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery

Multi-Level Canonical Correlation Analysis for Standard-Dose PET Image Estimation

Positron emission tomography (PET) images are widely used in many clinical applications such as tumor detection and brain disorder diagnosis. To obtain PET images of diagnostic quality, a sufficient amount of radioactive tracer has to be injected into a living body, which will inevitably increase the risk of radiation exposure. On the other hand, if the tracer dose is considerably reduced, the quality of the resulting images would be significantly degraded. It is of great interest to estimate a standard-dose PET (S-PET) image from a low-dose one in order to reduce the risk of radiation exposure and preserve image quality. This may be achieved through mapping both standard-dose and low-dose PET data into a common space and then performing patch based sparse representation. However, a one-size-fits-all common space built from all training patches is unlikely to be optimal for each target S-PET patch, which limits the estimation accuracy. In this paper, we propose a data-driven multi-level Canonical Correlation Analysis (mCCA) scheme to solve this problem. Specifically, a subset of training data that is most useful in estimating a target S-PET patch is identified in each level, and then used in the next level to update common space and improve estimation. Additionally, we also use multi-modal magnetic resonance images to help improve the estimation with complementary information. Validations on phantom and real human brain datasets show that our method effectively estimates S-PET images and well preserves critical clinical quantification measures, such as standard uptake value