Ante-mortem and Post-mortem Diagnosis Modalities and Phylogenetic Analysis of Rabies Virus in Domestic and Wild Animals of Gujarat, India.

In the present study, total of 32 ante-mortem (AM) samples (saliva = 18 and corneal smears = 14) from six animal species (cattle = 5; camel = 1; goat = 1; horse = 1; buffalo = 4; dog = 6) and 28 post-mortem (PM) samples of domestic (cattle = 6; camel = 1; goat = 1; buffalo = 5; dog = 7) and wild animals (lion = 4, mongoose = 2; bear = 1; leopard = 1) were examined for rabies diagnosis in Gujarat, India. Direct fluorescent antibody test (dFAT) and reverse transcriptase polymerase chain reaction (RT-PCR) were applied on AM samples, whereas along with dFAT and RT-PCR, histopathological examination, immunohistochemistry (IHC) and real time PCR (qPCR) were used for PM diagnosis. Nucleotide sequencing of full nucleoprotein (N) and glycoprotein (G) genes were carried out upon representative amplicons. In AM examination, 7/18 saliva and 5/14 corneal impressions samples were found positive in dFAT and 8/18 saliva samples were found positive in RT-PCR. In PM examination, 14/28 samples showed positive results in dFAT and IHC with unusual large fluorescent foci in two samples. In histopathology, 11/28 samples showed appreciable lesion and Negri bodies were visible in 6 samples, only. Out of 23 brain samples examined. 12 samples were found positive in N gene RT-PCR and qPCR, and 10 samples in G gene RT-PCR. Phylogenetic analysis of N gene revealed that test isolates (except sample ID: lion-1; lion, Gir) form a close group with sequence ID, KM099393.1 (Mongoose, Hyderabad) and KF660246.1 (Water Buffalo, Hyderabad) which was far from some south Indian and Sri Lankan isolates but similar to Indian isolates from rest of India and neighboring countries. In G gene analysis, the test isolates form a close group with sequence ID, KP019943.1. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01126-0.

Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics.

We present a quantum chemical analysis of the 18F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the SN2 process, focusing on the role of the -OH functional groups facilitating the reactions. We found that the counter-cation TBMA+ acts as a bifunctional promoter: the -OH groups function as a bidentate 'anchor' bridging the nucleophile [18F]F- and the -OTs leaving group or the third -OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile SN2 18F-fluorination.

Metabolic engineering and synthetic biology for isoprenoid production in Escherichia coli and Saccharomyces cerevisiae.

Isoprenoids, often called terpenoids, are the most abundant and highly diverse family of natural organic compounds. In plants, they play a distinct role in the form of photosynthetic pigments, hormones, electron carrier, structural components of membrane, and defence. Many isoprenoids have useful applications in the pharmaceutical, nutraceutical, and chemical industries. They are synthesized by various isoprenoid synthase enzymes by several consecutive steps. Recent advancement in metabolic engineering and synthetic biology has enabled the production of these isoprenoids in the heterologous host systems like Escherichia coli and Saccharomyces cerevisiae. Both heterologous systems have been engineered for large-scale production of value-added isoprenoids. This review article will provide the detailed description of various approaches used for engineering of methyl-D-erythritol-4-phosphate (MEP) and mevalonate (MVA) pathway for synthesizing isoprene units (C5) and ultimate production of diverse isoprenoids. The review particularly highlighted the efforts taken for the production of C5-C20 isoprenoids by metabolic engineering techniques in E. coli and S. cerevisiae over a decade. The challenges and strategies are also discussed in detail for scale-up and engineering of isoprenoids in the heterologous host systems.Key points• Isoprenoids are beneficial and valuable natural products.• E. coli and S. cerevisiae are the promising host for isoprenoid biosynthesis.• Emerging techniques in synthetic biology enabled the improved production.• Need to expand the catalogue and scale-up of un-engineered isoprenoids. Metabolic engineering and synthetic biology for isoprenoid production in Escherichia coli and Saccharomyces cerevisiae.

Tractostorm: The what, why, and how of tractography dissection reproducibility.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called "virtual dissection." Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC-ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real-life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and "virtual dissection" across various laboratories and hospitals. Intra-rater agreement (Dice score) was approximately 0.77, while inter-rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.

Patient-specific 3-dimensionally printed models for neurosurgical planning and education.

OBJECTIVE: Advances in 3-dimensional (3D) printing technology permit the rapid creation of detailed anatomical models. Integration of this technology into neurosurgical practice is still in its nascence, however. One potential application is to create models depicting neurosurgical pathology. The goal of this study was to assess the clinical value of patient-specific 3D printed models for neurosurgical planning and education. METHODS: The authors created life-sized, patient-specific models for 4 preoperative cases. Three of the cases involved adults (2 patients with petroclival meningioma and 1 with trigeminal neuralgia) and the remaining case involved a pediatric patient with craniopharyngioma. Models were derived from routine clinical imaging sequences and manufactured using commercially available software and hardware. RESULTS: Life-sized, 3D printed models depicting bony, vascular, and neural pathology relevant to each case were successfully manufactured. A variety of commercially available software and hardware were used to create and print each model from radiological sequences. The models for the adult cases were printed in separate pieces, which had to be painted by hand, and could be disassembled for detailed study, while the model for the pediatric case was printed as a single piece in separate-colored resins and could not be disassembled for study. Two of the models were used for patient education, and all were used for presurgical planning by the surgeon. CONCLUSIONS: Patient-specific 3D printed models are useful to neurosurgical practice. They may be used as a visualization aid for surgeons and patients, or for education of trainees.

Groundwater flow and arsenic contamination transport modeling for a multi aquifer terrain: Assessment and mitigation strategies.

Arsenic contaminated shallow aquifers evaluation, mitigation, and management strategies are the challenging task to all the hydrologist and provide a safe drinking water demand in the Holocene age, alluvial aquifers. To manage and mitigate such problems, we used numerical groundwater modeling software (GMS 10.2), for the development of 3D transient state predictive (groundwater flow and contaminant transport) conceptual model for two topographically different arsenic contaminated regions. The models were built by using the measured hydro-geological data, empirical values, and equations. Groundwater flow calibration, sensitivity analyses, and validation were performed for each soil parameters, varying boundary conditions and for alternate meteorological scenarios. The MODFLOW results suggested that, the distribution of As contaminant was directly controlled by the complex hydrostratigraphy, surface water bodies and indirectly controlled by the change in meteorological conditions. The MT3DMS model, for As contaminant transport, used for the assessment of shallow and deeper aquifers. The results showed that the downward movement of As has made the deeper aquifer unsafe for drinking water and irrigation purposes. However, the aquifers and regions with high flushing capability, negligible vertical hydraulic conductivity can be delineated as As safe groundwater source, irrespective of their sediment color. Therefore, for the geogenic source of As, both the simulation results inferred that to estimate and mitigate As contaminant groundwater aquifers or regions, the numerical modeling solution is a technically viable means an effective decision-making tool.

Generalized q-sampling imaging fiber tractography reveals displacement and infiltration of fiber tracts in low-grade gliomas.

PURPOSE: Low-grade gliomas (LGGs) are slow growing brain tumors that often cause displacement and/or infiltration of the surrounding white matter pathways. Differentiation between infiltration and displacement of fiber tracts remains a challenge. Currently, there is no reliable noninvasive imaging method capable of revealing such white matter alteration patterns. We employed quantitative anisotropy (QA) derived from generalized q-sampling imaging (GQI) to identify patterns of fiber tract alterations by LGGs. METHODS: Sixteen patients with a neuropathological diagnosis of LGG (WHO grade II) were enrolled. Peritumoral fiber tracts underwent qualitative and quantitative evaluation. Contralateral hemisphere counterparts were used for comparison. Tracts were qualitatively classified as unaffected, displaced, infiltrated or displaced, and infiltrated at once. The average QA of whole tract (W), peritumoral tract segment (S), and their ratio (S/W) were obtained and compared to the healthy side for quantitative evaluation. RESULTS: Qualitative analysis revealed 9 (13.8%) unaffected, 24 (36.9%) displaced, 13 (20%) infiltrated, and 19 (29.2%) tracts with a combination of displacement and infiltration. There were no disrupted tracts. There was a significant increase in S/W ratio among displaced tracts in the pre-operative scans in comparison with the contralateral side. QA values of peritumoral tract segments (S) were significantly lower in infiltrated tracts. CONCLUSION: WHO grade II LGGs might displace, infiltrate, or cause a combination of displacement and infiltration of WM tracts. QA derived from GQI provides valuable information that helps to differentiate infiltration from displacement. Anisotropy changes correlate with qualitative alterations, which may serve as a potential biomarker of fiber tract integrity.

Enzymatic Formation of a Skipped Methyl-Substituted Octaprenyl Side Chain of Longestin (KS-505a): Involvement of Homo-IPP as a Common Extender Unit.

Longestin (KS-505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). Biochemical analysis of Lon23, a methyltransferase involved in the biosynthesis of longestin, demonstrated that it methylates homoisopentenyl diphosphate (homo-IPP) to afford (3Z)-3-methyl IPP. This compound, along with IPP, is selectively accepted as extender units by Lon22, a geranylgeranyl diphosphate (GGPP) synthase homologue, to yield dimethylated GGPP (dmGGPP). The absolute configuration of dmGGPP was determined to be (4R,12R) by degradation and chiral GC analysis. These findings allowed us to propose an enzymatic sequence for key steps of the biosynthetic pathway of the unusual homoterpenoid longestin.

A diffusion spectrum imaging-based tractographic study into the anatomical subdivision and cortical connectivity of the ventral external capsule: uncinate and inferior fronto-occipital fascicles.

PURPOSE: The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) are major fronto-capsular white matter pathways. IFOF connects frontal areas of the brain to parieto-occipital areas. UF connects ventral frontal areas to anterior temporal areas. Both fascicles are thought to subserve higher language and emotion roles. Controversy pertaining to their connectivity and subdivision persists in the literature, however. METHODS: High-definition fiber tractography (HDFT) is a non-tensor tractographic method using diffusion spectrum imaging data. Its major advantage over tensor-based tractography is its ability to trace crossing fiber pathways. We used HDFT to investigate subdivisions and cortical connectivity of IFOF and UF in 30 single subjects and in an atlas comprising averaged data from 842 individuals. A per-subject aligned, atlas-based approach was employed to seed fiber tracts and to study cortical terminations. RESULTS: For IFOF, we observed a tripartite arrangement corresponding to ventrolateral, ventromedial, and dorsomedial frontal origins. IFOF volume was not significantly lateralized to either hemisphere. UF fibers arose from ventromedial and ventrolateral frontal areas on the left and from ventromedial frontal areas on the right. UF volume was significantly lateralized to the left hemisphere. The data from the averaged atlas was largely in concordance with subject-specific findings. IFOF connected to parietal, occipital, but not temporal, areas. UF connected predominantly to temporal poles. CONCLUSION: Both IFOF and UF possess subdivided arrangements according to their frontal origin. Our connectivity results indicate the multifunctional involvement of IFOF and UF in language tasks. We discuss our findings in context of the tractographic literature.

Stepwise case selection using Guy's stone score reduces complications during percutaneous nephrolithotomy training.

INTRODUCTION: Traditional percutaneous nephrolithotomy (PCNL) training involved subjective award of cases to the trainee. We restructured this according to the Guy's stone score (GSS) such that each trainee stepwise completed 25 cases of each grade before progressing. This study compares the outcomes of training with traditional versus stepwise approach. METHODS: Four hundred consecutive cases equally distributed for two trainees in each group were compared in terms of complications (Clavien-Dindo), stone free rate (SFR), operative and fluoroscopy time. External comparison was also done against a benchmark surgeon. Multivariable regression model was created to compare SFR and complications while adjusting for comorbidity, Amplatz size, access tract location, number of punctures, body mass index, stone complexity, and training approach. RESULTS: The distribution of cases in terms of calculus complexity was similar. Overall, in comparison to traditional training, stepwise training had significantly shorter median operative time (100 vs. 120 min, P < 0.05), fluoroscopy time (136 vs. 150 min, P < 0.05) and fewer overall (29.5% vs. 43.5%, P < 0.005) as well as major complications (3% vs. 8.5%, P - 0.029), though initial SFR was higher but not statistically significant (77% vs. 71.5%). On multivariable analyses, stepwise training was independently associated with lower complications (odds ratio 0.46 [0.20-0.74], P - 0.0013) along with GSS grade, number of punctures, and Amplatz size. Stepwise training had similar fluoroscopy time, major complications and final clearance rate compared to expert surgeon. CONCLUSIONS: PCNL has a learning curve specific for each grade of calculus complexity and stepwise training protocol improves outcomes.

One molecule of ionic liquid and tert-alcohol on a polystyrene-support as catalysts for efficient nucleophilic substitution including fluorination.

The tert-alcohol and ionic liquid solvents in one molecule [mim-(t)OH][OMs] was immobilized on polystyrene and reported to be a highly efficient catalyst in aliphatic nucleophilic substitution using alkali metal salts. Herein, we investigated the catalytic activity of a new structurally modified polymer-supported tert-alcohol functionalized imidazolium salt catalyst in nucleophilic substitution of 2-(3-methanesulfonyloxypropyoxy)naphthalene as a model substrate with various metal nucleophiles. The tert-alcohol moiety of the ionic liquid with a hexyl chain distance from polystyrene had a better catalytic activity compared to the other resin which lacked an alkyl linker and tert-alcohol moiety. We found that the maximum [mim-(t)OH][OMs] loading had the best catalytic efficacy among the tested polystyrene-based ionic liquids (PSILs) in nucleophilic fluorination. The catalytic efficiency of the PS[him-(t)OH][OMs] as a phase transfer catalyst (PTC) was determined by carrying out various nucleophilic substitutions using the corresponding alkali metal salts from the third to sixth periodic in CH3CN or tert-BuOH media. The scope of this protocol with primary and secondary polar substrates containing many heteroatoms is also reported. This PS[him-(t)OH][OMs] catalyst not only enhances the reactivity of alkali metal salts and reduces the formation of by-products but also affords high yield with easy isolation.

Simvastatin nanoemulsion for improved oral delivery: design, characterisation, in vitro and in vivo studies.

Simvastatin is poorly bioavailable as it is practically insoluble in water and shows dissolution rate-limited absorption. Therefore, the present study was aimed at preparing nanoemulsion (NE) of simvastatin for improving its solubility and/or dissolution rate for enhancing its bioavailability. The NEs were evaluated for particle size (PS), zeta potential, transmission electron microscopy (TEM), viscosity, in vitro release and stability studies. The optimised NE showed PS of 132 ± 9 nm and zeta potential of 17.1 ± 1.2 mV. TEM studies demonstrated spherical shape and size of the globules. In vitro release studies showed increased dissolution rate of NE compared with plain drug (PD). Pharmacokinetic studies showed relative bioavailability of simvastatin NE was 369.0% with respect to PD suspension. Pharmacodynamic studies conducted in hyperlipidemic rats showed that significant decrease in the total cholesterol and triglyceride levels for NE as compared with PD proving improvement in bioavailability. In conclusion, NE has great potential for improving bioavailability of poorly water-soluble drugs like simvastatin.

Countrywide monitoring of absorbed dose rate in air due to outdoor natural gamma radiation in India.

The Indian Environmental Radiation Monitoring Network continuously monitors, throughout India, the absorbed dose rate in air due to outdoor natural gamma radiation, by using Geiger-Mueller detector-based standalone environmental radiation monitors. The network consists of 546 monitors spread across 91 monitoring locations distributed all over the country. In this paper, the countrywide long-term monitoring results are summarised. The measured mean dose rate of the monitoring locations followed a log-normal distribution and ranged from 50 to 535 nGy.h-1 with a median value of 91 nGy.h-1. Due to outdoor natural gamma radiation, the average annual effective dose was estimated to be 0.11 mSv.y-1.

Sequential enzymatic epoxidation involved in polyether lasalocid biosynthesis.

Enantioselective epoxidation followed by regioselective epoxide opening reaction are the key processes in construction of the polyether skeleton. Recent genetic analysis of ionophore polyether biosynthetic gene clusters suggested that flavin-containing monooxygenases (FMOs) could be involved in the oxidation steps. In vivo and in vitro analyses of Lsd18, an FMO involved in the biosynthesis of polyether lasalocid, using simple olefin or truncated diene of a putative substrate as substrate mimics demonstrated that enantioselective epoxidation affords natural type mono- or bis-epoxide in a stepwise manner. These findings allow us to figure out enzymatic polyether construction in lasalocid biosynthesis.

Antibiotic Susceptibility Pattern of Canine Coagulase Positive and Coagulase Negative Staphylococcus spp. in a Hot and Dry Region of India.

The emergence of antimicrobial resistance among Staphylococcus spp. isolated from clinical cases of canines should be continuously monitored hence the present study was formulated to ascertain the antibiotypes and methicillin resistance in coagulase positive and coagulase negative staphylococci of canine skin and associated mucous membrane affections from a hot and dry region of India. A total of 165 clinical samples were collected and Staphylococcus aureus was identified by conventional bacteriological methods and PCR. Antibiotic susceptibility test was done against commercially available antibiotic impregnated discs as per Clinical and Laboratory Standards Institute (CLSI) method. Methicillin resistance was determined by plate methods and then via PCR of mecA gene. These 165 samples yielded, 88 (53.33%) isolates of genus Staphylococcus and 46 S. aureus and 51/88 (57.95%) isolates were coagulase positive staphylococci. Total 55 (62.5%) isolates showed susceptibility to Ceftriaxone/Sulbactum, 37 (42.05%) to Ciprofloxacin, 26 (29.55%) to Oxacillin, 24 (27.27%) to Penicillin, and 10 (11.36%) to Gentamicin. Total 21 methicillin-resistant S. aureus (MRSA) and 12 methicillin-resistant coagulase negative staphylococci (MRCoNS) were found on phenotypic basis whereas the mecA gene was detected in 6/21 MRSA and 2/12 MRCoNS isolates. Staphylococcus spp. showed increased level of resistance against commonly used antibiotics. The higher prevalence of methicillin resistance found with phenotypic methods than to mecA PCR indicates toward additional mechanisms responsible for emergence of MRS, especially in CoNS.

20%-efficient polycrystalline Cd(Se,Te) thin-film solar cells with compositional gradient near the front junction.

Bandgap gradient is a proven approach for improving the open-circuit voltages (VOCs) in Cu(In,Ga)Se2 and Cu(Zn,Sn)Se2 thin-film solar cells, but has not been realized in Cd(Se,Te) thin-film solar cells, a leading thin-film solar cell technology in the photovoltaic market. Here, we demonstrate the realization of a bandgap gradient in Cd(Se,Te) thin-film solar cells by introducing a Cd(O,S,Se,Te) region with the same crystal structure of the absorber near the front junction. The formation of such a region is enabled by incorporating oxygenated CdS and CdSe layers. We show that the introduction of the bandgap gradient reduces the hole density in the front junction region and introduces a small spike in the band alignment between this and the absorber regions, effectively suppressing the nonradiative recombination therein and leading to improved VOCs in Cd(Se,Te) solar cells using commercial SnO2 buffers. A champion device achieves an efficiency of 20.03% with a VOC of 0.863 V.

Solid lipid nanoparticles and nanosuspension formulation of Saquinavir: preparation, characterization, pharmacokinetics and biodistribution studies.

Solid lipid nanoparticles (SLNs) and nanosuspensions (NSs) have shown great promise for improving bioavailability of poorly water-soluble drugs. This study was aimed to develop SLNs and NS of Saquinavir (SQ) for improvement in bioavailability. These formulations were characterized and their pharmacokinetics and biodistribution in mice were evaluated. Saquinavir-loaded SLNs (SQSLNs) showed particle size 215 ± 9 nm and entrapment efficiency 79.24 ± 1.53%, while solid-state studies (differential scanning calorimetry and X-ray diffraction) indicated entrapment of the drug in SLNs. Saquinavir NS (SNS) showed particle size 344 ± 16 nm with fourfold increase in saturation solubility and its solid-state studies showed reduction in crystallinity. Pharmacokinetics and biodistribution studies of orally administered SQSLN and SNS in mice exhibited higher plasma level concentration compared to saquinavir microsuspension (SMS). The relative bioavailabilities for SNS and SQSLN were 37.39% and 66.53%, respectively, compared to 18.87% bioavailability obtained after administration of SMS, indicating suitability of nanoparticulate formulations for improving bioavailability.

Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: Recent Progress and Future Prospects.

In the field of 18F-chemistry for the development of radiopharmaceuticals for positron emission tomography (PET), various labeling strategies by the use of prosthetic groups have been implemented, including chemoselective 18F-labeling of biomolecules. Among those, chemoselective 18F-fluoroglycosylation methods focus on the sweetening of pharmaceutical radiochemistry by offering a highly valuable tool for the synthesis of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. A previous review covered the various 18F-fluoroglycosylation methods that were developed and applied as of 2014 (Maschauer and Prante, BioMed. Res. Int. 2014, 214748). This paper is an updated review, providing the recent progress in 18F-fluoroglycosylation reactions and the preclinical application of 18F-glycoconjugates, including small molecules, peptides, and high-molecular-weight proteins.

18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach.

The 18F syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [18F]fluoride from H2[18O]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [18F]fluoride is commonly achieved by phase transfer catalysts (PTC) in aqueous solution, which makes azeotropic drying indispensable. The ideal PTC is characterized by a slightly basic nature, its capacity to elute [18F]fluoride with anhydrous solvents, and its efficient complex formation with [18F]fluoride during subsequent labeling. Herein, we developed tri-(tert-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for 18F-fluorination reactions. The favorable elution efficiency of [18F]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high 18F-recoveries of 96-99%. 18F-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing 18F-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to 18F-fluorination reactions and could be used for elution of [18F]fluoride with MeOH, omitting an additional base and azeotropic drying prior to 18F-labeling. We speculate that the tert-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [18F]fluoride during nucleophilic 18F-fluorination.

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host's in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors.