RE: Nasal Vaccines9 Feb 2022 10:33
This article from 2014 mentions the role of TLRs and also more importantly Flagellin, which we know is the reason for the powerful effects of 0518
as potent stimulators of dendritic cells.
This would be LBPs delivered to the gut where there is a pathway to induce mucosal immunity.
"Mucosal vaccination via the modulation of mucosal DCs
Mucosal immune responses are most efficiently induced by the administration of vaccines onto mucosal surfaces, whereas vaccines injected deep into skin tissue (subcutaneously) or muscle (intramuscularly) are usually poor inducers of mucosal immunity and are therefore less effective against infection at mucosal surfaces.
Mucosal vaccines given at mucosal surfaces must overcome the same physical host defense challenges as microbial pathogens: They are diluted in mucosal secretions, captured in a sticky barrier of mucus, attacked by degradation enzymes and excluded by tight epithelial barriers. Therefore, relatively large doses of vaccine are required for mucosal delivery. Vaccine formulations for targeted delivery must have an effective mucosal adjuvant to surmount tolerance and mimic infectious conditions. For several reasons, live attenuated mucosal vaccines are likely to be more effective than injected vaccines. First, because they are naturally particulate, antigens will selectively adhere to M-cell mucosal surfaces, enabling efficient uptake. Second, via the use of pattern molecules, they should efficiently stimulate innate signals on innate effector cells (especially DCs). Third, they will elicit appropriate adaptive immune responses for clearance of the target pathogen. Another DC-targeted vaccine strategy is the use of appropriate adjuvants, such as DC growth factor or TLR ligand, that are expressed on mucosal DCs (Table 2). Plasmids encoding Flt3 ligand and CpG oligonucleotide selectively target CD8a+ DCs and pDCs, respectively, when administered nasally.34, 35, 36 CD8a+ DCs promote TH2 cytokine production, whereas pDCs induce TH1 cytokine production to elicit co-administered antigen-specific IgA antibody responses and cell-mediated immunity. In one study, when soluble antigen plus cholera toxin was applied to intact skin, MLN langerin+ DCs mediated gut IgA production in an RA-dependent manner.30 Similar to the use oftranscutaneous systemic vaccination to induce gut immunity, systemic immunization with flagellin can recruit CD103+ DCs into MLNs and subsequently induce intestinal IgA antibody responses.37 Intra-tracheal application of LPS-treated immunodominant CTL epitope-loaded DCs is also a promising strategy for generating CTLs that are protective against respiratory infections caused by intracellular pathogens".
https://www.nature.com/articles/emm201416
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