Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier

Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.

Potentiating Lung Mucosal Immunity Through Intranasal Vaccination

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches. Here, we consider the route of immunization as a critical factor in eliciting tissue resident memory (Trm) populations that are not a target of current licensed intramuscular vaccines. Intranasal vaccination has the potential to boost tissue resident B and T cell populations that reside within specific niches of the upper and lower respiratory tract. Within these niches, Trm cells are poised to respond rapidly to pathogen re-encounter by nature of their anatomic localization and their ability to rapidly deliver anti-pathogen effector functions. Unique features of mucosal immunity in the upper and lower respiratory tracts suggest that antigen localized to these regions is required for the elicitation of protective B and T cell immunity at these sites and will need to be considered as an important attribute of a rationally designed intranasal vaccine. Finally, we discuss outstanding questions and areas of future inquiry in the field of lung mucosal immunity.

Parenteral Antioxidant Supplementation at Birth Improves the Response to Intranasal Vaccination in Newborn Dairy Calves

Newborn calves experience oxidative stress throughout the first month of their life, which is known to decrease lymphocyte functions relevant to vaccine responsiveness. Thus, this study aimed to determine the extent to which parenteral antioxidant supplementation given at birth improves the response to an intranasal viral vaccine in the first month of life of newborn dairy calves. For this, 21 calves were randomly assigned at birth to one of two commercially available antioxidant micronutrient supplements or a placebo group receiving 0.9% sterile saline (n = 7/group). Serum and nasal secretion samples were collected before administration of treatments and an intranasal vaccine against respiratory viruses (bovine herpesvirus type 1, bovine syncytial respiratory virus, and parainfluenza 3), and once weekly for the first four weeks of age. Systemic redox balance was determined in serum. Immunoglobulin A specific for bovine herpesvirus 1 and bovine syncytial respiratory virus was quantified in nasal secretions as a proxy to intranasal vaccine responsiveness. Our results showed that parenteral administration of antioxidants at birth improved calves’ redox balance. Additionally, calves receiving antioxidant supplementation had higher concentrations of immunoglobulin A in their nasal secretions than calves in the control group. Thus, we conclude that supplementation of calves with antioxidants at birth could be a practical strategy to improve intranasal vaccine response. Future larger studies should evaluate the extent to which this increased mucosal response to intranasal vaccination could result in decreased calf morbidity and mortality.

Oral Bacteria Combined with an Intranasal Vaccine Protect from Influenza A Virus and SARS-CoV-2 Infection

Intranasal vaccination induces the nasal IgA antibody which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines.

A Review on Modern Use of Intranasal Vaccination in the Treatment of SARS-COV-2

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for efficient SARS coronavirus 2 (SARS-CoV-2) preventative vaccines to limit the burden and spread of SARS-CoV-2 in humans. Intranasal immunization is a promising technique for preventing COVID-19 because the nasal mucosa acts as a first line of defense against SARS-CoV-2 entrance before the virus spreads to the lungs. Nasal vaccination has many advantages over traditional vaccine administration methods. These include the simplicity of administration without the use of needles, which decreases the risks of needle stick injuries and disposal. This channel also provides simple access to a crucial portion of the immune system that can stimulate other mucosal sites throughout the body. By targeting immunoglobulin A (IgA), antibodies found only in the mucosa, an intranasal vaccination would elicit immunological responses in the nose, throat, and lungs. Potential pathogens are trapped by the mucosa, which acts as a physical barrier to prevent them from entering the body. Given this, the intranasal vaccine would prevent virus transmission via exhaled droplets or aerosols because there would be no virus in the body to expel .There are several intranasal vaccines for protection against sars-cov2 are under preclinical and clinical trials .The key challenge is in Designing delivery strategies that take into account the wide range of diseases, populations, and healthcare delivery settings that stand to benefit from this unique mucosal route should be prioritized. Keywords: COVID-19, Intranasal vaccine, Immunoglobulin A, Permeation

Global Variation in the Recommended Age for Influenza Vaccination in Children

Influenza vaccination is critical to prevent severe influenza in children, especially for whom with high risks and underlying diseases. However, vaccination schedule is not standardized, and different in each country/region. In Japan, vaccination is available for children aged 6 months and older and is recommended from the age of 1 year. In the United States, routine annual influenza vaccination for all children aged 6 months and older are recommended. In the United Kingdom, routine influenza vaccination has been recommended for children after the age of 2 to 3 years, and typically administered as a single dose of live intranasal vaccine. Many countries and regions considered the high-risk groups and recommended the once, but twice shot with the appropriate interval are recommended.

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, and emergence of SARS-CoV-2 variants or entirely new viruses. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided weight loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

Intranasal Vaccination Strategy to Control the COVID-19 Pandemic from a Veterinary Medicine Perspective

The world is currently facing an ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease is a highly contagious respiratory disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current control measures used by many countries include social distancing, wearing face masks, frequent hand washing, self-isolation, and vaccination. The current commercially available vaccines are injectable vaccines, although a few intranasal vaccines are in trial stages. The reported side effects of COVID-19 vaccines, perceptions towards the safety of the vaccines, and frequent mutation of the virus may lead to poor herd immunity. In veterinary medicine, attaining herd immunity is one of the main considerations in disease control, and herd immunity depends on the use of efficacious vaccines and the vaccination coverage in a population. Hence, many aerosol or intranasal vaccines have been developed to control veterinary respiratory diseases such as Newcastle disease, rinderpest, infectious bronchitis, and haemorrhagic septicaemia. Different vaccine technologies could be employed to improve vaccination coverage, including the usage of an intranasal live recombinant vaccine or live mutant vaccine. This paper discusses the potential use of intranasal vaccination strategies against human COVID-19, based on a veterinary intranasal vaccine strategy.