Nanoliposomal Vaccine Research Articles

A self-adjuvanting anti-tumor nanoliposomal vaccine based on fluorine-substituted MUC1 glycopeptide.

Herein, a self-adjuvanting fluorinated MUC1-based nanoliposomal antitumor vaccine was constructed for the first time. Both the tumor-associated antigen and the mode of its presentation affect the immune response for antitumor vaccines.

AE36 HER2/neu-derived peptide linked to positively charged liposomes with CpG-ODN as an effective therapeutic and prophylactic vaccine for breast cancer

In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combine.

Impact of PCSK9 Immunization on Glycemic Indices in Diabetic Rats.

Methods To prepare the anti-PCSK9 vaccine, a peptide construct called Immunogenic Fused PCSK9-Tetanus (IFPT) was linked to the surface of nanoliposome carriers. Healthy rats received four subcutaneous injections of the vaccine at biweekly intervals. Two weeks after the last vaccination, anti-PCSK9 antibody titers, PCSK9 targeting, and inhibition of PCSK9–low-density lipoprotein receptor (LDLR) interaction were evaluated. After verification of antibody generation, the immunized rats were intraperitoneally treated with a single dose (45 mg/kg) of streptozotocin (STZ) to induce diabetes mellitus. The levels of fasting blood glucose (FBG) were measured, and the oral glucose tolerance test (OGTT) as well as the insulin tolerance test (ITT) were carried out to assess glycemic status. At the end of the study, the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol concentrations were assayed. Histopathology examination of the liver and pancreas was also performed using the hematoxylin-eosin staining method. Results The prepared nanoliposomal vaccine could strongly induce anti-PCSK9 antibodies in the vaccinated rats. Within one week following the STZ injection, the FBG level was lower in the vaccinated group vs. diabetic control group (49% (−171.7 ± 35 mg/dL, p < 0.001)). In the OGTT, the injected rats showed improved glucose tolerance as reflected by the reduction of blood glucose levels over 180 min, compared with the diabetic controls. Moreover, the ITT demonstrated that, after the insulin injection, blood glucose concentration declined by 49.3% in the vaccinated group vs. diabetic control group. Expectedly, the vaccinated rats exhibited lower (-26.65%, p = 0.03) plasma LDL-C levels compared with the diabetic controls. Histopathology examination of pancreas tissue demonstrated that the pancreatic islets of the vaccinated rats had a slight decline in the population of β-cells and few α-cells. Normal liver histology was also observed in the vaccinated rats. Conclusion PCSK9 inhibition through the liposomal IFPT vaccine can improve the glucose and insulin tolerance impairments as well as the lipid profile in diabetes.

Evaluation of survival rate using liposome containing soluble antigens (SA) against Toxoplasma gondii infection in BALB/c mice

Objective(s)Toxoplasma gondii, an obligate intracellular protozoan parasite, is widespread across the world. It causes congenital disease and abortion in humans and domestic animals. One of the major concerns in parasitology, thus, is an effective vaccine development to control Toxoplasmosis.Materials and MethodsIn the present research, a nano-liposomal vaccine containing soluble antigens (SA) was designed to evaluate the immunity and protective efficacy against T. gondii infection in BALB/c mice. Soluble antigens (SA) were achieved from tachyzoites, encapsulated in the liposome, and investigated via scanning electron microscope. Three times with 2-week intervals, BALB/c mice were immunized subcutaneously with different formulations. The level of protection against infection was assessed through the percent survival survey of BALB/c mice after challenge with tachyzoites of T. gondii RH strain; also, the type of generated immune response was determined by evaluating the generation of cytokine (IFN-γ, IL-4) and titration of IgG isotypes.ResultsThe immunization with liposome DSPC+ SA and liposome DSPC+ Imiquimod + SA induced a substantial increase in anti-Toxoplasma IgG antibody as compared to the PBS group (p <0.05). The IgG2a and IFN-γ secretion highest levels were seen with liposome DSPC+ Imiquimod + SA more than the control group (p <0.01) and (p <0.0001), respectively. After challenge with tachyzoites, less mortality was detected in the immunized mice by liposome DSPC + Imiquimod + SA that was meaningfully different (p <0.01) in comparison to other groups.ConclusionVaccination with liposome DSPC + Imiquimod + SA showed more survival rate and cellular immune reaction against T. gondii.

Preparation and Characterization of A Nanoliposomal Vaccine of pcLACK Candidate Against Cutaneous Leishmaniasis.

Leishmaniasis is a public health problem and endemic in countries of the tropics and subtropics. An ongoing project with naked LACK (Leishmania homolog of receptors for activated C-kinase) demonstrated that this case of the gene is entirely susceptible to immune response and it does enter the cells effectively. This study aimed at developing a procedure to prepare a type of lipid nanoparticles overloaded with plasmid LACK (pcLACK) for usage as Leishmania major (L. major) nanoliposomal vaccine. The single-gene expression plasmid of pcLACK was encoded in the LACK antigen. Nanoparticles were set up by thin film procedure using cationic lipids 1, 2-Dioleoyl- 3-Trimethylammonium propane (DOTAP), 1, 2-Dioleoyl-snGlycero-3-Phosphoethanolamine (DOPE), and cholesterol in a molar proportion of 2:1:1 molar ratio. Using dynamic light scattering, the particle diameters of empty and loaded lipoplexes were measured in triplicate. The zeta-potential (ζ) was measured with the same instrument using the zeta potential mode as the average of 20 measurements by diluting the particles into a low salt buffer. The results of the sustainability studies of Liposome-pcLACK formulation showed that there were no significant physical changes up to the 30th day of stability study at the storage condition of 4°C. However, there were significant changes in the formulation content during storage at 25°C for 30 days (204.2±0.90 at Day 30 compared with 207.2±0.26 nm at Day 0). It was observed that the prepared nanoliposomal formulation had more stability under refrigeration. Immunostimulatory cationic lipids bearing a pcLACK encapsulation could serve as an effective delivery system.

Nanoliposomal vaccine containing long multi-epitope peptide E75-AE36 pulsed PADRE-induced effective immune response in mice TUBO model of breast cancer

The main goal of peptide-based cancer vaccines is to induce the immune system and activation of effective T cell responses against cancerous cells. Nevertheless, the potency of peptide vaccines is insufficient in most of cases and had limited clinical success. Therefore, the optimization of peptide-based cancer vaccine is essential to achieve powerful therapeutic outcomes. One strategy to enhanced potency of peptide vaccines and induce strong immune responses is the preparation of multi-epitope peptide formulation containing both Th- and cytotoxic T lymphocyte–induced responses epitope using suitable delivery system. For this reason, we studied the effect of Dioleoylphosphatidylethanolamine-containing liposomal vaccine composed of a mixture of short peptides AE36 and E75 (HER2/neu-derived peptides) and long multi-epitope peptide E75-AE36 (linkage of short peptides) in combination with a Pan HLA-DR epitope (PADRE) peptide. These formulations were examined using a series of subcutaneously injection to HER-2+ TUBO-tumoured mice in prophylactic and therapeutic model. We observed that mice vaccinated with liposomal long peptide in combination with PADRE resulted in the superior induction of CD4+ and CD8+ T cells responses and significantly enhanced production of IFN-γ compared with liposomal short peptides and non-liposomal peptides formulations. Moreover, liposome-long peptide with PADRE led to the considerable reduction of tumour growth and lifespan induction in mouse model. In conclusion, our study indicated that liposomal formulation containing long multi-epitope peptide E75-AE36 with PADRE could be used as an effective multi-epitope prophylactic/therapeutic vaccine to generate potent antigen-specific CD8+ T-cell immune response and may be introduced as a possible candidate peptide vaccine for breast cancer.

MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer

Liposomal peptide-based vaccines can potentially suppress cancer cells proliferation in the host. To enhance the effectiveness of vaccination against cancer, additional strategies should also be employed. One strategy to promote peptide-based vaccine efficacy and induce powerful immune responses, is simultaneous activation of CD4+ and CD8+ T cells. To address this problem, we tested the efficacy of a nano-liposomal vaccine containing P5 peptide, a cytotoxic T lymphocytes (CTL) specific peptide derivative of rat HER2/neu protein, Pan HLA-DR (PADRE) peptide, a universal CD4+ T helper cell epitope and monophosphoryl lipid A (MPL) a toll-like receptor 4 ligand. We observed potent CD8+ T cell immune responses in TUBO mice vaccinated with liposomal P5 peptide in combination with PADRE and MPL. Also, this formulation remarkably improved anti-tumor effects against cells overexpressing HER2 in BALB/c mice compared to liposomal vaccine containing P5 only. Furthermore, we found that vaccination with Lip-P5- Integrated PADRE-MPL formulation significantly induced IFN-γ production, increased CD8+ T cells numbers and enhanced survival compared to other groups of treated mice. In conclusion, our study indicated that Lip-P5-Integrated PADRE-MPL, after further confirmatory investigations, could be employed as a promising vaccine to generate potent CTL anti-tumor immune responses that could be beneficial to treatment of HER2+ breast cancer.

P435 HER2/neu-derived peptide conjugated to liposomes containing DOPE as an effective prophylactic vaccine formulation for breast cancer

The present study was aimed to develop an effective nanoliposomal vaccine delivery system with P435 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The nanoliposome formulation composed of DSPC/DSPG/Chol/DOPE and monophosphoryl lipid A was used as an adjuvant. Liposomal formulations were prepared and their physical properties were characterized. Anti-tumoral efficacy of formulations was evaluated by immunization of tumor-bearing BALB/c mice and the generated immune response was studied by using ELISpot and flow cytometry analysis. The results of the study demonstrated Lip + DOPE + P535 formulation caused the lowest tumor size and the longest survival time in TUBO mice model and could make it a promising candidate in developing effective vaccines against HER2-positive breast cancers.

Nanoliposomes carrying HER2/neu-derived peptide AE36 with CpG-ODN exhibit therapeutic and prophylactic activities in a mice TUBO model of breast cancer

This study was designed to prepare and characterize nanoliposomal vaccine formulation encapsulating AE36 HER2/neu-derived peptide with or without CpG and evaluate the immunologic and therapeutic responses of that in BALB/c mice model of Her2 overexpressing breast cancer. AE36 was encapsulated in liposomes composed of DOTAP, DOPE and Cholesterol (DDC) or DD with. The formulations could induce both CD8+ and CD4+ responses and stimulate production of cytokines which was detected by Enzyme-linked immunospot assay (ELISpot) kits, cytotoxicity test and intracellular cytokine assay by flow cytometry. The formulation showed both therapeutic and prophylactic effects in BALB/c mice bearing Her2+ breast cancer. DDC+CpG showed the best effect in prophylactic study and DD+pG showed the best effect in therapeutic study, which both of them decreased the size of tumors significantly. The engineered nanoliposomes containing AE36 could be a candidate vaccine for the treatment or prophylaxis of HER2+ breast cancer and merits further investigation.