Oral Vaccine Delivery Research Articles

Surface functionalization of PLGA nanoparticles for potential oral vaccine delivery targeting intestinal immune cells

This study aimed to develop surface modified PLGA nanocarriers protecting a protein-based antigen in the stomach to enable potential release of the antigen at target intestinal sites. PLGA nanoparticles (NPs) were prepared by double emulsion and solvent evaporation techniques while surface functionalization was performed using polyethylene glycol (PEG), sodium alginate (ALG) and Eudragit L100 (EUD) with ovalbumin (OVA) as a model protein antigen. Nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), and stability in simulated gastric fluid (SGF)/simulated intestinal fluid (SIF). Structural integrity of released OVA was analyzed by circular dichroism (CD) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), while cytotoxicity against Jurkat cells was determined using MTT assay. Surface functionalized PLGA NPs protected the protein in SGF and SIF better than the non-functionalized NPs. Average size of OVA encapsulated NPs was between 235 and 326 nm and were spherical. FTIR band change was observed after surface modification and the surface modified NPs showed sustained OVA release compared with the uncoated NPs. The secondary structure of OVA released after 96 h remained intact and MTT assay showed >80 % cell viability after 72 h while unmodified and surface modified NPs achieved 17 % and 48 % mucin binding respectively. In conclusion, surface modified PLGA NPs have been shown to be safe for potential oral protein-based vaccine delivery.

Polysaccharide-based hydrogels for drug delivery and wound management: A review

Introduction Hydrogels are three-dimensional crosslinked networks of hydrophilic polymers, capable of absorbing large quantities of water or aqueous fluids. Polysaccharide-based hydrogels (PBHs) offer several advantages over their synthetic counterparts. Their natural origin contributes to their non-toxicity, high biocompatibility, and in vivo biodegradability. Their properties can be tuned finely to obtain hydrogels with desired mechanical, structural, and chemical properties. Areas covered Such versatile characteristics have potentiated the use of PBHs for the delivery of drugs, vaccines, protein & peptide therapeutics, genes, cells, probiotics, bacteriophages, and other therapeutic agents. Recent advances in hydrogel-based formulations such as nanogels, microgels, microneedles, hydrogel beads, nanocarrier-loaded hydrogels, and complexation hydrogels have enabled the precise delivery of a wide range of therapeutics. This review aims to give a holistic overview of hydrogels in the delivery of a variety of therapeutics through different routes, which is seldom covered in other reviews. Expert opinion PBHs have been used to enable the oral delivery of vaccines and other biologicals, thereby allowing self-administration of life-saving vaccines, saving countless lives, especially during public health emergencies. There is a lack of commercialized wound dressings for the treatment of chronic wounds. PBH-based wound dressings, especially those based on chitosan and loaded with actives and growth factors have the potential to help in the long-term treatment of such wounds. Recent developments in the 3D printing of hydrogels can enable the quick and large-scale production of drug-loaded hydrogels.

Cost of oral cholera vaccine delivery in a mass immunization program for children in urban Bangladesh

Cholera poses a substantial health burden in the developing world due to both epidemic and endemic diseases. The World Health Organization recommends oral cholera vaccines for mass vaccination campaigns in addition to traditional prevention practices and treatments in resource-poor settings. In many developing countries like Bangladesh, the major challenge behind implementing mass vaccination campaigns concerns the affordability of the oral cholera vaccine (OCV). Vaccination of children with OCV is not only an impactful approach for controlling cholera at the population level and reducing childhood morbidity but is also considered more cost-effective than vaccinating all ages. The aim of the study was to estimate the cost of an OCV campaign for children from a societal perspective using empirical study. A total of 66,311 children aged 1 to 14 years old were fully vaccinated with two doses of the OCV Shanchol while 9,035 individuals received one dose of this vaccine. The estimated societal cost per individual for full vaccination was US$ 6.11, which includes the cost of vaccine delivery estimated at US$ 1.95. The cost per single dose was estimated at US$ 2.86. The total provider cost for full vaccination was estimated at US$ 6.01 and the recipient cost at US$ 0.10. Our estimation of OCV delivery costs for children was relatively higher than what was found in a similar mass OCV campaign for all age groups, indicating that there may be additional cost factors to consider in targeted vaccine campaigns. This analysis provides useful benchmarks for the possible costs related to delivery of OCV to children and future OCV cost-effectiveness models should factor in these possible cost disparities. Attempts to reduce the cost per dose are likely to have a greater impact on the cost of similar vaccination campaigns in many resource-poor settings.

Recombinant Helicobacter pylori Vaccine Delivery Vehicle: A Promising Tool to Treat Infections and Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) has become a global public health threat. Experts agree that unless proper actions are taken, the number of deaths due to AMR will increase. Many strategies are being pursued to tackle AMR, one of the most important being the development of efficient vaccines. Similar to other bacterial pathogens, AMR in Helicobacter pylori (Hp) is rising worldwide. Hp infects half of the human population and its prevalence ranges from <10% in developed countries to up to 90% in low-income countries. Currently, there is no vaccine available for Hp. This review provides a brief summary of the use of antibiotic-based treatment for Hp infection and its related AMR problems together with a brief description of the status of vaccine development for Hp. It is mainly dedicated to genetic tools and strategies that can be used to develop an oral recombinant Hp vaccine delivery platform that is (i) completely attenuated, (ii) can survive, synthesize in situ and deliver antigens, DNA vaccines, and adjuvants to antigen-presenting cells at the gastric mucosa, and (iii) possibly activate desired compartments of the gut-associated mucosal immune system. Recombinant Hp vaccine delivery vehicles can be used for therapeutic or prophylactic vaccination for Hp and other microbial pathogens.

Oral vaccination of fish against vibriosis using spore-display technology.

Oral vaccines are highly demanded by the aquaculture sector, to allow mass delivery of antigens without using the expensive and labor-intensive injectable vaccines. These later require individual handling of fish, provoking stress-related mortalities.One possible strategy to create injection-free vaccine delivery vehicles is the use of bacterial spores, extremely resistant structures with wide biotechnological applications, including as probiotics, display systems, or adjuvants. Bacterial spores, in particular those of Bacillus subtilis, have been shown to behave as mucosal vaccine adjuvants in mice models. However, such technology has not been extensively explored against fish bacterial disease.In this study, we used a laboratory strain of B. subtilis, for which a variety of genetic manipulation tools are available, to display at its spores surface either a Vibrio antigenic protein, OmpK, or the green fluorescence protein, GFP. When previously vaccinated by immersion with the OmpK- carrying spores, zebrafish survival upon a bacterial challenge with V. anguillarum and V. parahaemolyticus, increased up to 50 - 90% depending on the pathogen targeted. Further, we were able to detect anti-GFP-antibodies in the serum of European seabass juveniles fed diets containing the GFP-carrying spores and anti-V. anguillarum antibodies in the serum of European seabass juveniles fed the OmpK-carrying spores containing diet. More important, seabass survival was increased from 60 to 86% when previously orally vaccinated with in-feed OmpK- carrying spores. Our results indicate that B. subtilis spores can effectively be used as antigen-carriers for oral vaccine delivery in fish.

Modeling the potential economic benefits of an oral SARS-CoV-2 vaccine during an outbreak of COVID-19

BackgroundGiven patient preferences, the choice of delivery modality for vaccines against SARS-CoV-2 has the potential to significantly impact both health and economic consequences of an outbreak of COVID-19. This study models the projected health and economic impact of an oral COVID-19 vaccine in the United States during an outbreak occurring between December 1, 2021 and February 16, 2022. MethodsA cost-of-illness economic decision analysis model is utilized to assess both the health and economic impact of an oral vaccine delivery platform compared with the status quo deployment of existing intramuscular vaccines against COVID-19. Health impact is assessed in terms of predicted cases, deaths, hospitalization days, intensive care unit admission days, and mechanical ventilation days averted. Health system economic impact is assessed based on the cost-of-illness averted derived from the average daily costs of medical care, stratified by severity. Productivity loss due to premature death is estimated based on regulatory analysis guidelines proposed by the U.S. Department of Health and Human Services. ResultsBased upon preference data, we estimate that the availability of an oral COVID-19 vaccine would increase vaccine uptake from 214 million people to 232 million people. This higher vaccination rate was estimated to result in 2,497,087 fewer infections, 25,709 fewer deaths, 1,365,497 fewer hospitalization days, 186,714 fewer Intensive Care Unit (ICU) days, and 80,814 fewer patient days requiring mechanical ventilation (MV) compared with the status quo. From a health systems perspective, this translates into $3.3 billion in health sector costs averted. An additional $139-$450 billion could have been averted in productivity loss due to a reduction in premature deaths.ConclusionsVaccine delivery modalities that are aligned with patient preferences have the ability to increase vaccination uptake and reduce both the health and economic impact of an outbreak of COVID-19. We estimate that the total economic impact of productivity loss and health systems cost-of-illness averted from an oral vaccine could range from 0.6%-2.9% of 2021 U.S, Gross Domestic Product (GDP).

Development of fermented milk using food-grade recombinant Lactococcus lactis NZ3900

Fermented milk has been associated with the improvement of human health for decades. Food-grade Lactococcus lactis NZ3900 is a potential host for producing and delivering various biologics, including oral vaccines, hence it could enhance the functionality of fermented milk as a starter culture. A cultured fermented milk product was developed in this study using the food-grade recombinant L. lactis NZ3900 harboring plasmid pNZ8149. Response surface methodology was used to optimize the inoculum concentration (5–15% v/v), fermentation temperature (23–37 °C), and fermentation time (18–30 h) to enhance the viability, acidification activity, viscosity, and minimize syneresis of the L. lactis NZ3900-fermented milk using response surface methodology. The optimal inoculum concentration and fermentation conditions for L. lactis NZ3900-fermented milk are 12.5% (v/v) inoculum, 28 °C fermentation temperature, and 30 h of fermentation time, resulting in higher viability (9.64 log10 CFU/mL), acidification activity (pH 4.42, 0.78% titratable acidity), viscosity (11,096.9 mPa·s), and comparable syneresis (63.62%) against commercial fermented milk products. This shows that food-grade L. lactis NZ3900 can be used as a starter culture, and NZ3900-fermented milk could be used as a functional drink for oral vaccine delivery.

Recombinant Lactococcus lactis Expressing Grass Carp Reovirus VP6 Induces Mucosal Immunity Against Grass Carp Reovirus Infection.

Grass carp haemorrhagic disease caused by grass carp reovirus II is a serious disease of the aquaculture industry and vaccination is the only effective method of GCRV protection. In this study, Lactococcus lactis was used as oral vaccine delivery to express the GCRV II VP6 protein. We evaluated the protective efficacy of the live vaccine strain to induce mucosal immune protection. After oral administration, the recombinant strains remained in the hindgut for antigen presentation and increased the survival rate 46.7% and the relative percent survival 42.9%, respectively versus control vaccination. Though L. lactis alone can induce the inflammatory response by stimulating the mucosal immune system, the recombinant L. lactis expressing VP6 greatly enhanced nonspecific immune responses via expression of immune related genes of the fish. Furthermore, both systemic and mucosal immunity was elicited following oral immunization with the recombinant strain and this strain also elicited an inflammatory response and cellular immunity to enhance the protective effect. L. lactis can therefore be utilized as a mucosal immune vector to trigger high levels of immune protection in fish at both the systemic and mucosal levels. L. lactis is a promising candidate for oral vaccine delivery.

Tailoring functional nanoparticles for oral vaccine delivery: Recent advances and future perspectives

The oral vaccine has attracted much interest due to easy administration, induction of local and systemic immune responses, and pain relief. Nowadays, functional nanoparticles and nanocomposites consisting of inorganic and organic materials as carriers or adjuvants have shown the enhanced antigen absorption in the gut and improved immune response via oral routes. This review summarizes the advances and challenges of functional nanoparticles and nanocomposites for oral vaccine delivery, including the key barriers of the mucosal delivery, the transport mechanisms of these nanoformulation through the epithelial layer, and the key physicochemical properties of the nanoparticles and nanocomposites for antigen delivery. Various nanoformulations including nanoparticles and nanocomposites were further exemplified. The summary and expert opinions in designing functional nanoformulation for efficient oral vaccine delivery are provided.

Development of a peptide vaccine against hookworm infection: Immunogenicity, efficacy, and immune correlates of protection

Approximately 400 million individuals are infected with hookworms globally. Protective vaccines are needed to prevent reinfections, which often occur after drug treatment in endemic areas. Ideal vaccines are highly efficacious and well tolerated, and do not present risks to patient safety. Peptide vaccines can generate specific, highly protective responses because they focus on minimal antigenic target(s) with a specific immunoprotective mechanism. Necator americanus aspartyl protease 1 (Na-APR-1) is one of the most promising hookworm vaccine antigens. The neutralizing epitope p3 (TSLIAGPKAQVEAIQKYIGAEL), together with universal the TH epitope P25 (KLIPNASLIENCTKAEL), has been used previously to produce peptide vaccines and was found to protect BALB/c mice against rodent hookworm infections, resulting in worm burden reductions of up to 98%. However, because of extensive digestion in the gastrointestinal tract, large oral vaccination doses were necessary to achieve this level of efficacy. We sought to overcome the limitations of oral vaccine delivery and to investigate protective efficacy and immune correlates of protection. Herein, we examined 5 different peptide vaccines following intraperitoneal injection, to compare their efficacy with that of the clinical protein antigen APR-1. BALB/c mice were immunized with p3-P25-based antigen that was adjuvanted with (1) lipid core peptide, (2) polymethyl methacrylate, (3) linear polyleucine, and (4) branched polyleucine (BL10), or with (5) CpG/aluminum hydroxide adjuvant (alum)-adjuvanted control and protein-based (6) CpG/alum-adjuvanted Na-APR-1. The mice sera, saliva, and feces were sampled for immune response evaluation. The immunized mice were further challenged via hookworm larvae infection, and protection was evaluated by conducting intestinal hookworm counts. BL10 and lipid core peptide generated the highest serum anti-Na-APR-1 IgG and fecal anti-APR-1 IgG titers, but only BL10 generated significant fecal anti-Na-APR-1 IgA titers. Upon challenge, immunization with CpG/alum-adjuvanted p3-P25, BL10, and lipid core peptide provided the highest worm burden reductions of 75%, 77%, and 59%, respectively, whereas the group immunized with Na-APR-1 had only modest worm reduction of 26%. The relationships between serum anti-Na-APR-1 IgG, fecal anti-Na-APR-1 IgA and IgG, and worm burden reduction were established with R2 values greater than or equal to 0.9, and the crucial role of both anti-Na-APR-1 IgG and IgA responses was identified. We demonstrated for the first time that p3-based vaccine candidates are safer and can deliver higher protection against hookworm infection compared with the clinical vaccine candidate, Na-APR-1.

Enhancing Stability and Mucoadhesive Properties of Chitosan Nanoparticles by Surface Modification with Sodium Alginate and Polyethylene Glycol for Potential Oral Mucosa Vaccine Delivery.

Background: The present study aimed to fabricate surface-modified chitosan nanoparticles with two mucoadhesive polymers (sodium alginate and polyethylene glycol) to optimize their protein encapsulation efficiency, improve their mucoadhesion properties, and increase their stability in biological fluids. Method: Ionotropic gelation was employed to formulate chitosan nanoparticles and surface modification was performed at five different concentrations (0.05, 0.1, 0.2, 0.3, 0.4% w/v) of sodium alginate (ALG) and polyethylene glycol (PEG), with ovalbumin (OVA) used as a model protein antigen. The functional characteristics were examined by dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM)/scanning transmission electron microscopy (STEM). Stability was examined in the presence of simulated gastric and intestinal fluids, while mucoadhesive properties were evaluated by in vitro mucin binding and ex vivo adhesion on pig oral mucosa tissue. The impact of the formulation and dissolution process on the OVA structure was investigated by sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD). Results: The nanoparticles showed a uniform spherical morphology with a maximum protein encapsulation efficiency of 81%, size after OVA loading of between 200 and 400 nm and zeta potential from 10 to 29 mV. An in vitro drug release study suggested successful nanoparticle surface modification by ALG and PEG, showing gastric fluid stability (4 h) and a 96 h sustained OVA release in intestinal fluid, with the nanoparticles maintaining their conformational stability (SDS-PAGE and CD analyses) after release in the intestinal fluid. An in vitro mucin binding study indicated a significant increase in mucin binding from 41 to 63% in ALG-modified nanoparticles and a 27–49% increase in PEG-modified nanoparticles. The ex vivo mucoadhesion showed that the powdered particles adhered to the pig oral mucosa. Conclusion: The ALG and PEG surface modification of chitosan nanoparticles improved the particle stability in both simulated gastric and intestinal fluids and improved the mucoadhesive properties, therefore constituting a potential nanocarrier platform for mucosal protein vaccine delivery.

Nanocarriers-Assisted Needle-Free Vaccine Delivery Through Oral and Intranasal Transmucosal Routes: A Novel Therapeutic Conduit.

Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.

Engineering Nano- and Microparticles as Oral Delivery Vehicles to Promote Intestinal Lymphatic Drug Transport.

Targeted oral delivery of a drug via the intestinal lymphatic system (ILS) has the advantages of protecting against hepatic first-pass metabolism of the drug and improving its pharmacokinetic performance. It is also a promising route for the oral delivery of vaccines and therapeutic agents to induce mucosal immune responses and treat lymphatic diseases, respectively. This article describes the anatomical structures and physiological characteristics of the ILS, with an emphasis on enterocytes and microfold (M) cells, which are the main gateways for the transport of particulate delivery vehicles across the intestinal epithelium into the lymphatics. A comprehensive overview of recent advances in the rational engineering of particulate vehicles, along with the challenges and opportunities that they present for improving ILS drug delivery, is provided, and the mechanisms by which such vehicles target and transport through enterocytes or M cells are discussed. The use of naturally sourced materials, such as yeast microcapsules and their derived polymeric β-glucans, as novel ILS-targeting delivery vehicles is also reviewed. Such use is the focus of an emerging field of research. Their potential use in the oral delivery of nucleic acids, such as mRNA vaccines, is proposed.

Advancedoral vaccine delivery strategies for improving the immunity.

Infectious diseases continue to inflict a high global disease burden. The consensus is that vaccination is the most effective option against infectious diseases. Oral vaccines have unique advantages in the prevention of global pandemics due to their ease of use, high compliance, low cost, and the ability to induce both systemic and mucosal immune responses. However, challenges of adapting vaccines for oral administration remain significant. Foremost among these are enzymatic and pH-dependent degradation of antigens in the stomach and intestines, the low permeability of mucus barrier, the nonspecific uptake of antigens at the intestinal mucosal site, and the immune suppression result from the elusive immune tolerance mechanisms. Innovative delivery techniques promise great potential for improving the flexibility and efficiency of oral vaccines. A better understanding of the delivery approaches and the immunological mechanisms of oral vaccine delivery systems may provide new scientific insight and tools for developing the next-generation oral vaccine. Here, an overview of the advanced technologies in the field of oral vaccination is proposed, including mucus-penetrating nanoparticle (NP), mucoadhesive delivery vehicles, targeting antigen-presenting cell (APC) nanocarriers and enhanced paracellular delivery strategies and so on. Meanwhile, the mechanisms of delivery vectors interact with mucosal barriers are discussed.

Oral Immunization of Larvae and Juvenile of Lumpfish (Cyclopterus lumpus) against Vibrio anguillarum Does Not Influence Systemic Immunity.

Vibrio anguillarum, a marine bacterial pathogen that causes vibriosis, is a recurrent pathogen of lumpfish (Cyclopterus lumpus). Lumpfish is utilized as a cleaner fish in the Atlantic salmon (Salmo salar) aquaculture in the North Atlantic region because of its ability to visualize and prey on the ectoparasite sea lice (Lepeophtheirus salmonis) on the skin of Atlantic salmon, and its performance in cold environments. Lumpfish immunity is critical for optimal performance and sea lice removal. Oral vaccine delivery at a young age is the desired method for fish immunization because is easy to use, reduces fish stress during immunization, and can be applied on a large scale while the fish are at a young age. However, the efficacy of orally delivered inactivated vaccines is controversial. In this study, we evaluated the effectiveness of a V. anguillarum bacterin orally delivered to cultured lumpfish and contrasted it to an intraperitoneal (i.p.) boost delivery. We bio-encapsulated V. anguillarum bacterin in Artemia salina live-feed and orally immunized lumpfish larvae. Vaccine intake and immune response were evaluated by microscopy and quantitative polymerase chain reaction (qPCR) analysis, respectively. qPCR analyses showed that the oral immunization of lumpfish larvae resulted in a subtle stimulation of canonical immune transcripts such as il8b, il10, igha, ighmc, ighb, ccl19, ccl20, cd8a, cd74, ifng, and lgp2. Nine months after oral immunization, one group was orally boosted, and a second group was both orally and i.p. boosted. Two months after boost immunization, lumpfish were challenged with V. anguillarum (7.8 × 105 CFU dose−1). Orally boosted fish showed a relative percentage of survival (RPS) of 2%. In contrast, the oral and i.p. boosted group showed a RPS of 75.5% (p < 0.0001). V. anguillarum bacterin that had been orally delivered was not effective in lumpfish, which is in contrast to the i.p. delivered bacterin that protected the lumpfish against vibriosis. This suggests that orally administered V. anguillarum bacterin did not reach the deep lymphoid tissues, either in the larvae or juvenile fish, therefore oral immunization was not effective. Oral vaccines that are capable of crossing the epithelium and reach deep lymphoid tissues are required to confer an effective protection to lumpfish against V. anguillarum

Recent advances in nano/microparticle-based oral vaccines.

BackgroundVaccines are often recognized as one of the most cost-effective public health interventions in controlling infectious diseases. Most pathogens infiltrate the body from mucosal sites, primarily from the oral and pulmonary region and reach the systemic circulation where disease manifestation starts. Traditional needle-based vaccines are usually not capable of inducing immunity at the mucosal sites where pathogen infiltrates start, but induces systemic immunity. In contrast to needle-based vaccines, mucosally administered vaccines induce immunity at both the mucosal sites and systemically. The oral route of immunization is the most convenient way to administer the vaccines. However, due to the complicated and hostile gastrointestinal structure and environment, vaccines need to overcome major hurdles while retaining their stability and immunogenicity.Area coveredThis review will briefly discuss different barriers to oral vaccine development. It gives a brief overview of different types of nano/microparticle-based oral vaccines and discusses how physicochemical characteristics of the particles influence overall immunity after oral immunization.Expert opinionFormulation strategies using novel lipid and polymer-based nano/microparticle platforms retain stability and antigenicity of vaccines against the harsh gastrointestinal condition. The physicochemical properties of particles can be uniquely tailored to prolong the release of antigens, and attached ligands (M-cells and APC-ligands) can precisely target uptake by immune cells. These represent viable strategies for efficient delivery of oral vaccines.

Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases.

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

Cationic chitosan-modified silica nanoparticles for oral delivery of protein vaccine.

Mesoporous silica nanoparticles coated with Chitosan are exploited here as a potential carrier for oral vaccine delivery. Bovine serum albumin (BSA) was used as a protein antigen model to reveal the carrier property. Chitosan-coated BSA-loaded silica NPs had particle size 345 ± 60 nm with a cationic surface charge of 18.28 ± 0.71 mV. The encapsulation efficiency, drug loading was 25.34 ± 0.76 and 20.21 ± 0.48%, respectively. Transmission electron microscopy investigation showed the spherical shape of NPs, also confirmed surface coating around modified nanoparticles (NPs), and nitrogen absorption/desorption isotherm confirmed mesostructured inside the NPs. Fourier transform infrared spectroscopy did not show any physiochemical interactions between excipients and formulations. The structural stability of antigen after release from NPs was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and chitosan-coated silica NPs exhibited a slow-release pattern. The results of in vivo experiments presented that chitosan-mesoporous silica NPs could induce a robust immune response in mice, indicating that chitosan-mesoporous silica NPs might be used as a promising carrier for oral vaccine delivery.

Evaluation of oral phytogenic microbeaded Newcastle Disease vaccine delivery in indigenous chicken

ABSTRACT This study describes the evaluation of microbeaded oral vaccine delivery for Newcastle Disease (ND) in village chicken. Microbeads containing vaccine were prepared by ionotropic-gelation technique using aluminum sulfate. Lasota Vaccine strain (2 g) was well mixed with Boswellia caterii gum extract at ratio 1:1. The wet beads were washed twice with distilled water and dried at 37℃ overnight. Microbeads without vaccine were prepared as control. A tablet dissolution machine was used to evaluate peak adhesion time (PAT). Sixty local chickens sourced from a recognized breeder were separated into four groups for in in-vivo evaluation. Group A was administered with the bead-loaded vaccine mixed with their feed, group B had vaccine alone administered in their drinking water, group C had the bead alone mixed with their feed, and group D, which served as negative control received no vaccination against ND nor gum beads. The PAT on both trachea and jejunum was 4 ± 10 hours. Post-vaccination antibody titer revealed higher response in group B than (6.6) in group A (5.3); the micro-beaded vaccine gave delayed but enhanced and prolonged immune response. This noninvasive and easy to administer method may be useful in the prevention of ND outbreaks in backyard poultry production.

Bilosomes: Superior Vesicular Carriers

In the current era, many formulations have been designed in the form of vesicular carriers like liposomes and niosomes which have been proved to be one of the potential candidates for drug delivery by the oral route but due to the gastrointestinal environment i.e. pH, presence of enzymes, and bile salts, their use is limited. Because of these difficulties, research is being done to increase the stability and efficacy of the drug. Thus bilosomes have been developed as a potential vesicular carrier system for oral vaccine delivery, transdermal and parenteral targeted drug delivery. The present article covers various aspects related to the novel vesicular system that is based on bile salts called bilosomes, for targetted drug delivery systems. It includes information related to bilosome composition, formulation techniques, characterization methods, applications in oral immunization as vaccine delivery approach and advantages over conventional nanocarriers such as liposomes and niosomes. It also focuses on the stability and applications of bilosomes along with scalability and potentiality in biomedical field of oral immunization against various dreadful diseases.