Review: The Nose as a Route for Therapy. Part 2 Immunotherapy

Abstract

The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant “reservoir” for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.

Post-exposure intranasal IFNα suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons

“…Intranasal Type I IFN therapy has been explored for various respiratory viruses, including endemic viruses (rhinovirus and influenza) and recently SARS-CoV2 to modulate the severity of disease [43]. Similarly, Type I IFN treatment has been evaluated in other viruses considered to be potential biological weapons, including other encephalitic alphaviruses and hemorrhagic filoviruses, arenaviruses, phleboviruses [44][45][46][47][48][49][50][51].…”

Post-exposure intranasal IFNα suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons

“…Intranasal Type 1 IFN therapy has been explored for various respiratory viruses, including endemic viruses (rhinovirus and influenza) and recently SARS-CoV2 to modulate the severity of disease [37]. However, our student presents the first demonstration of IFN administration to treat a potential aerosolized biological weapon.…”

Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment

“…Topically applied antihistamines induce downregulation of ICAM -1 expression on epithelial cells and thereby reduce eosinophil activation and allergen-induced inflammation ( 46 , 47 ). However, using ICAM-1 as an anchor for bispecific antibodies for allergy treatment is a rather new concept ( 48 ). In a proof of principle study, antibody conjugates bispecific for ICAM-1 and pollen allergens were applied to capture and immobilize allergens via ICAM-1 to the apical surface of epithelial cells and thereby prevent allergen penetration through the epithelial barrier ( 21 ).…”