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In this research, a structural variant of muramyl dipeptide (MDP) is designed wherein, the entire N-acetyl group was replaced by a bio-isosteric 1,2,3-triazole moiety with serinol lipid substitution at 4th position. The protecting groups such as benzyl and benzylidine were removed sequentially to evolve three novel derivatives with increasing polarity as seen in the MDP-lipid 21-23 derivatives. A synthesis strategy involving triazolyl click chemistry to combine MDP scaffold to the serinol lipid head group is developed. The new derivatives were characterized using NMR, ESI-MS and MALDI. Preliminary data from in vitro screening of the compounds inferred the immuno-potentiating properties.

Toll-like receptors-7 and -8 are expressed abundantly on antigen-presenting cells, and their agonists make potential adjuvant candidates for the development of new efficacious vaccines.

CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production. When immunized with quadrivalent split influenza virus in BALB/c mice, the novel ceramide analogues with a longer oligo (ethylene glycol) chain length induced significant levels of antibody (IgG) with Th1-polarized immune response.

Research on amalgamation of an antigen with a delivery system for developing a potent mucosal vaccine that elicits both cellular and humoral response has captured immense attention these days. Cationic delivery systems being the first choice for mucosal antigen delivery, despite being effective, are associated with inherent problems like cytotoxicity. Therefore, the quest for developing a precise system that can effectively deliver antigen to immune cells without adverse toxic effect has led to the use of partial cationic systems which are mostly humoral immune mediators. The art of fine-tuning cationic nature, avoiding side effects, and being immune responsive are the needs of the hour. Herein, we try to optimize the cationic nature of polycaprolactone (USFDA approved) by conjugating it with hydrazine. The polymer was modified using two stoichiometry ratios (5 and 10 equiv) of hydrazine monohydrate and characterized using FTIR and XRD. Free amine quantification of the modified polymers concluded that both the modified polymers had 232 and 457 μM/mg amine groups, respectively. A cytotoxicity assay performed using RAW 264.7 macrophages proved the safety of cationic polymers.

Two new secophragmalin-type limonoids, secotrichagmalins B (1) and C (2) along with two known compounds, were isolated from the fruits of Trichilia connaroides. The structures of the new compounds ...

A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of Pam

Nasal vaccine delivery systems are emerging alternatives to the conventional sub unit vaccine delivery systems owing to their ability to stimulate potent antigen specific humoral and cellular immune responses. Additional virtue of nasal delivery is its close proximity of immune cells to external epithelial layer which is the route of entry to pathogens. Toxicity of emulsion based vaccine delivery systems may be attributed to the presence of high quantities of surfactants used for stabilizing the emulsions. A safer approach would be to reduce physiologically unwanted surfactant burden in the emulsion to the bare limit to necessity. Oleic acid was used as oil phase due to its ability to enhance penetration of system in nasal mucosa. This emulsion was designed with the purpose that it activates the innate (TLR 4) and adaptive immune systems apart from performing its antigen delivery function. Proving the hypothesis, emulsion when immunized along with recombinant tetravalent dengue antigen has elicited a profound antigen specific humoral and cellular response. Antigen cross presenting and sustained release of antigen by emulsion is the key factor in shaping this immune response. Moreover, the dose sparing effect of emulsion has also been proven which has a crucial role in modern day vaccine delivery. This significant humoral and cellular response elicited proves the suitability of this emulsion system for enhancing the protective effect of vaccines against various intracellular pathogens.

Prolonged exposure to Ultra Violet Radiation (UVR) adversely alters the functions of many skin cell types causing skin cancer and photoaging, which had led to increase in demand for more safe and natural sunscreens against UVR. The present study focuses on production, structural characterization and evaluation of photoprotective nature of melanin pigment derived from lime dwelling Pseudomonas sp. Melanin was characterized by solubility, UV–Vis, FT-IR, 13C-CPMAS, ESI-MS spectroscopy, including particle size, melting point and elemental analyses. In vitro cytotoxicity and photo-protective effect of Pseudomonas derived melanin (Mel-P) against UV-B (Broad Band-BB) radiations were assessed on mouse fibroblasts NIH 3 T3 cell lines. Reactive Oxygen Species (ROS) generated in NIH 3 T3 cells upon UV-B (BB) exposure was determined and quantified by Fluorescent microscopic and Flow cytometric analyses. A natural melanin obtained from Pseudomonas sp. contains 5,6- dihydroxy indole 2-carboxyic acid (DHICA) as its basic constituent and possess typical properties of eumelanin as revealed by the characterization studies. Mel-P has shown cell viability of 61.33 ± 6.58% at the concentration of 500 μg/mL proving its non-cytotoxic effect. Owing to its anti-oxidant property, melanin efficiently protected the mouse fibroblast cells from UV-B (BB) irradiation in a dose dependant manner demonstrating its potential as an active photoprotective agent.

A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of Pam3CAG and screened for their potential as TLR2 agonistic adjuvants against HBsAg antigen. In vitro ligand induced TLR2 signal activation was observed with all the analogues upon treatment with HEK blue TLR2 cell lines. Conjugate derived from ribose (6e), which exhibited pronounced HBsAg specific antibody (IgG) titer also shown enhanced CD8+ population indicating superior cell mediated immunity compared to standard adjuvant Pam3CSK4. Further, docking studies revealed ligand induced heterodimerization between TLR1 and 2. Overall, the result indicates the usefulness of novel conjugates as potential vaccine adjuvant.

Emulsions play an important role in present-day subunit vaccine delivery. Squalane-based emulsion was formulated using surfactants viz., Pluronic F68, Span 85 along with Murabutide (MB) as immunepotentiator. Particle size and zetapotential of the final optimized emulsion was found to be 134 nm and -13 mV, respectively. The in vitro cellular uptake studies performed using fluorescein isothiocyanate (FITC)-labeled ovalbumin (OVA) clearly revealed the rapid uptake of antigen in the presence of emulsion. The in vivo subcutaneous studies involving measurement of OVA-specific IgG antibody titers, Th1/Th2 cytokines were performed and a marked up regulation in IL-2, IL-12 and IFN-γ cytokines indicate Th1 immune response. Results supported that the squalane-based delivery system enhanced the uptake of the antigen by immune cells and elicited humoral as well as cell-mediated immune response in mice. These results indicate the promising application of the new squalane based oil-in-water (O/W) emulsion as capable vaccine delivery system useful for vaccine development.