Vaccination is an effective weapon for disease prevention and has been proven to significantly reduce the transmission of infections and the number of deaths worldwide. Almost all the approved vaccines are injectables and consequently parenteral vaccination is the most used method for their administration. The continuous emergence of new pathogens and the resistance of microorganisms increase the trend towards the development of new strategies to produce long-lasting immunity. Furthermore, the interest of the scientific community on the non-invasive methods of vaccine administration is risen constantly in the last decade. It is quite known that the nasal cavity is the first-contact area when the antigens are entered in the human body. Hence, the development of nasal vaccines may be a feasible alternative for a more effective immunisation.
The aim of this comprehensive review is to summarise and critically discuss the advances in the field of nasal vaccines to reveal their prospect as an alternative mode of immunisation. We assess the clinical applicability (protective and/or therapeutic) of IN vaccination in various diseases, such as influenza, pertussis, meningitis, hepatitis, based on in vitro, preclinical, and clinical studies.
Innovative Delivery Systems for Nasal Vaccines
Nanoparticulate Nasal vaccines
Several preclinical studies have focused on using nanoparticles as delivery systems and adjuvants either for intramuscular or nasal vaccination employing rodent or pig animal models. Particularly, the recent review of Nian et al. efficiently summarises the available types of mucosal adjuvants for nasal vaccines. Interestingly, through the nasal passage, nanoparticles can pass across mucus and interact directly with NALT cells. The stimulation of mucosal immune responses leads to the production of persistent immunological memory. The main reason for the use of nanoparticulate vaccines is their ability to protect antigens from the proteolytic degradation and improve the cellular distribution. The sustained release of the antigen in the mucosa can also be achieved by its formulation into nanoparticles. Thus, the probability of antigen uptake by the mucosal and lymphatic cells is increased. Modifications in physicochemical properties increase the stability of nanoparticles in biological fluids, allowing the prolonged presentation of the antigen in the body. Furthermore, various types of antigens can be entrapped and higher loading capacities, not only for the antigens but also for the adjuvants, can be achieved.
It is also feasible to modify the physicochemical properties of the particles, such as their charge, shape and size, rendering them ideal carriers for protein delivery, as well as for mimicking the viruses’ properties. Specifically, it has been shown that the spherical shape, size around 100 nm, cationic charge and hydrophobic character favours the uptake of nasally administered antigens from APCs. Another useful feature of nanoparticles is the ability to integrate TLR ligands in their surface, leading to a prolonged TLR signalling and reducing the number of antigens and adjuvants needed for an efficient immune response. Τhis cascade of events can also reduce the incidences of toxicity in non immune cells.
Nanoparticle Types Used in Nanoparticulate Nasal Vaccines
Polymeric nanoparticles. Nanoparticles from natural and synthetic polymers have been extensively studied as antigen delivery systems. Chitosan and PLGA molecules are the main representatives. Particularly, their mucoadhesive properties have been shown to enhance the immune response at both mucosal and systemic level. This is also verified in preclinical studies in which nasal immunizations were performed involving surface antigens of the hepatitis B virus (HBsAg), ovalbumin molecules and strains of the influenza A virus. In the study of Zaman et al. the self-assembling of amphiphilic dendrimers from polyacrylate molecules is described. These polymers could form IN subunit vaccines, giving a self-adjuvanting effect against systemic group A streptococcus infection. In the case of influenza A several chitosan-based mucosal vaccines have been tested in vivo, in poultry and pigs, having been delivered either orally or intranasally, triggering both mucosal and cellular immune responses.
