Oral Vaccine Development

The mRNA vaccine platform has offered the greatest potential in fighting the COVID-19 pandemic owing to rapid development, effectiveness, and scalability to meet the global demand. There are many other mRNA vaccines currently being developed against different emerging viral diseases. As with the current COVID-19 vaccines, these mRNA-based vaccine candidates are being developed for parenteral administration via injections. However, most of the emerging viruses colonize the mucosal surfaces prior to systemic infection making it very crucial to target mucosal immunity. Although parenterally administered vaccines would induce a robust systemic immunity, they often provoke a weak mucosal immunity which may not be effective in preventing mucosal infection. In contrast, mucosal administration potentially offers the dual benefit of inducing potent mucosal and systemic immunity which would be more effective in offering protection against mucosal viral infection. There are however many challe...

On screening of 647 serum samples from 72 pet dog, 42 mares, 333 cows (aborted 19, healthy breeding cows 194, cows with .__ pyrexia 120) and 200 buffalo (healthy breeding buffaloes 80, slaughtered for meat 120) a total of 51. 7% female and 25% male pet dogs, 48.3% cows with pyrexia of unknown origin (PUO), 47.4% cows those aborted within last 15 days of serum collection, 6.2% healthy breeding cows, 26.2% breeding mares, 10.7% breeding buffaloes and 8.3% buffaloes slaughtered for meat were positive for anti-Salmonella cytotoxin-I immunoglobulins in indirect enzyme linked immuno-sorbent assay (ELlSA). The prevalerice of anti-Salmonella IgGs was significantly high (X 2 <0.001) in dogs, mares and cows either aborted or sick with PUO than in other animals. Significantly high prevalence (X 2 <0.00 I) of anti-Sallllollella antibodies in cows either with PUO or abortion indicated the important role of salmonellosis in health and production of cattle in Northern lndia..

The present study on defined double deletion (DaroADhtrA) mutant (S30) of Salmonella enterica serovar Abortusequi evaluated it for safety, immunogenicity, and efficacy as a vaccine candidate in equids. The candidate strain was found safe in equids (foals, male and female horses and donkeys, and pregnant and nonpregnant mares) and induced good humoral and cell-mediated immunity on administration through oral route. The strain was not excreted in feces of vaccinated animals. The vaccine candidate administered orally (1 Â 10 11 cfu per animal) protected mares even after 180 days of inoculation against abortion on challenge with wild-type S. Abortusequi strain whereas in nonvaccinated control, all mares aborted. The vaccination in infertile mares resulted in regaining of fertility in 67%-80% thoroughbred mares at two different breeding farms. Further, the humoral immunity was transferred to foals from vaccinated mothers through colostrum, but no placental transfer was evident. Thus, the vaccine under study may be recommended for use in equids to control S. Abortusequi infection-associated abortions and also to enhance fertility of temporarily infertile mares in endemic areas.

Most childhood infections occur via the mucosal surfaces, however, parenterally delivered vaccines are unable to induce protective immunity at these surfaces. In contrast, delivery of vaccines via the mucosal routes can allow antigens to interact with the mucosa-associated lymphoid tissue (MALT) to induce both mucosal and systemic immunity. The induced mucosal immunity can neutralize the pathogen on the mucosal surface before it can cause infection. In addition to reinforcing the defense at mucosal surfaces, mucosal vaccination is also expected to be needle-free, which can eliminate pain and the fear of vaccination. Thus, mucosal vaccination is highly appealing, especially for the pediatric population. However, vaccine delivery across mucosal surfaces is challenging because of the different barriers that naturally exist at the various mucosal surfaces to keep the pathogens out. There have been significant developments in delivery systems for mucosal vaccination. In this review we pr...

Background Swine are the most important meat animal, famous for white meat, which are prepared as ham, bacon, gammon, sausages and pork. Swine are valuable animals and they are physiologically, immunologically and anatomically similar to humans and their organ can be transplanted to the humans. Due to modernization, the cultural food restriction has lost in the people of urban communities and among the younger generations in Nepal. Gradually changing feeding habit of Nepalese has proven pork to be a useful addition to the food menu. Not only 8.7 lakhs swine in Nepal but the global pig population which occupy 769.05 million are suffering every day from new challenges and threats from very harmful pathogens and diseases like swine dysentery, coccidiosis, swine influenza, etc. Swine influenza is highly contagious rapidly spreading zoonotic viral disease of pigs characterized by febrile respiratory disease often complicated with secondary bacterial infections. Vaccines are only tool for...

The present study on defined double deletion (DaroADhtrA) mutant (S30) of Salmonella enterica serovar Abortusequi evaluated it for safety, immunogenicity, and efficacy as a vaccine candidate in equids. The candidate strain was found safe in equids (foals, male and female horses and donkeys, and pregnant and nonpregnant mares) and induced good humoral and cell-mediated immunity on administration through oral route. The strain was not excreted in feces of vaccinated animals. The vaccine candidate administered orally (1 Â 10 11 cfu per animal) protected mares even after 180 days of inoculation against abortion on challenge with wild-type S. Abortusequi strain whereas in nonvaccinated control, all mares aborted. The vaccination in infertile mares resulted in regaining of fertility in 67%-80% thoroughbred mares at two different breeding farms. Further, the humoral immunity was transferred to foals from vaccinated mothers through colostrum, but no placental transfer was evident. Thus, the vaccine under study may be recommended for use in equids to control S. Abortusequi infection-associated abortions and also to enhance fertility of temporarily infertile mares in endemic areas.

Pioglitazone has been reported in the literature to have a substantial role in the improvement of overall cognition in a mouse model. With this in mind, the aim of this study was to determine the most efficacious route for the administration of Pioglitazone nanoparticles (PGZ-NPs) in order to promote drug delivery to the brain for the treatment of Alzheimer's disease. PGZ-loaded NPs were developed by the solvent displacement method. Parameters such as mean size, polydispersity index, zeta potential, encapsulation efficacy, rheological behavior, and short-term stability were evaluated. Ex vivo permeation studies were then carried out using buccal, sublingual, nasal, and intestinal mucosa. PGZ-NPs with a size around of 160 nm showed high permeability in all mucosae. However, the permeation and prediction parameters revealed that lag-time and vehicle/tissue partition coefficient of nasal mucosa were significantly lower than other studied mucosae, while the diffusion coefficient and theoretical steady-state plasma concentration of the drug were higher, providing biopharmaceutical results that reveal more favorable PGZ permeation through the nasal mucosa. The results suggest that nasal mucosa represents an attractive and non-invasive pathway for PGZ-NPs administration to the brain since the drug permeation was demonstrated to be more favorable in this tissue.

Most childhood infections occur via the mucosal surfaces, however, parenterally delivered vaccines are unable to induce protective immunity at these surfaces. In contrast, delivery of vaccines via the mucosal routes can allow antigens to interact with the mucosa-associated lymphoid tissue (MALT) to induce both mucosal and systemic immunity. The induced mucosal immunity can neutralize the pathogen on the mucosal surface before it can cause infection. In addition to reinforcing the defense at mucosal surfaces, mucosal vaccination is also expected to be needle-free, which can eliminate pain and the fear of vaccination. Thus, mucosal vaccination is highly appealing , especially for the pediatric population. However, vaccine delivery across mucosal surfaces is challenging because of the different barriers that naturally exist at the various mucosal surfaces to keep the pathogens out. There have been significant developments in delivery systems for mucosal vaccination. In this review we provide an introduction to the MALT, highlight barriers to vaccine delivery at different mucosal surfaces, discuss different approaches that have been investigated for vaccine delivery across mucosal surfaces, and conclude with an assessment of perspectives for mucosal vaccination in the context of the pediatric population.

Intimin is the primary adhesin protein of enterohemorrhagic Escherichia coli O157:H7, a pathogen carried by cattle and transmitted to humans via contaminated food and water. This work describes the rapid production of 1.3 kg dry weight of transgenic tobacco cells expressing the C-terminal 261 amino acids of intimin (Int261) for subsequent oral vaccine testing to reduce cattle colonization by E. coli O157:H7. Both a
stirred-tank bioreactor (60 L) and a less capital-intensive oxygenated carboy culture were shown feasible for generating this scale of transgenic plant tissue culture biomass. Antibiotic selection pressure was not required during scale-up to maintain Int261 expression over the 13-wk culture period. Extended medium autoclave times of up to 90 min used for bioreactor sterilization had only minimal impact on nutrient uptake, culture growth, and intimin expression. Plant tissue was transformed, produced in vitro, and available for feeding studies in a fraction of the time required to develop and grow transgenic plants.