As per the Crotty
study? Can't quite envisage a mechanism for doing that intranasally, though perhaps possible via some sort of slow-release skin patch (maybe MNP) proximal to the upper neck lymph nodes? (It's probably only practical intramuscularly or sub/trans-dermally). Can see various potential issues with that though, both in terms of delivery route (see below) and enthusiasm for uptake.
How would they achieve that ?
So I meant to highlight the following studies concerning intranasal vaccination and IgA a few weeks ago; they are worth noting and relevant to the question you pose.
Regarding vaccines for sterilising immunity, which will need to target the mucosal membranes in the respiratory tract, the route of administration matters (this has been
seen before).
First, (Mt Sinai, NYC) an investigation of mucosal antibody response in vaccinees.
Mucosal immune responses are critical to prevent respiratory infections.
A key characteristic of mucosal IgA antibodies is that they are mostly present in the form of multimers (eg
dimers). Multimeric IgA antibodies display higher anti-viral activity than monomeric IgA antibodies (the main form of systemic IgA, such as are found in sera and are induced by intramuscular vaccination).
[Mucosal IgA antibodies] are known to provide immediate immunity by eliminating respiratory pathogens before they pass through the mucosal barrier.
The researchers analysed sera and saliva from individuals (n=30, 7M/23F, age range 21-65) with and without COVID-19 at multiple timepoints before and after SARS-CoV-2 mRNA vaccination (a mix of BNT162b2 and mRNA-1273). They observed that vaccination induced only a weak mucosal IgA response in seronaive vaccinees, whilst convalescent vaccinees exhibited a strong mucosal IgA response.
The precise mechanism for the heterogeneity observed is yet to be determined (there are hypotheses that prior infection leads to better IgA homing to the respiratory tract; the immune system does indeed have 'memory'). Intranasal vaccination strategies that can successfully induce mucosal IgA "should be sought for control of the pandemic".
DOI: 10.1101/2021.12.06.21267352.
Then, (Yale/Mt Sinai, NYC) an interesting animal study, here specific to influenza but of relevance to SARS-CoV-2 as well, that illustrates some key advantages of intranasal vaccination over intramuscular (systemic) vaccination in respect of respiratory pathogens.
In an animal model they demonstrated that intranasal (but not systemic) immunisation (here with both protein-based and RNA-based vaccines) induced local IgA secretion in the mucous membranes of the respiratory tract, promoting a wide range of cells expressing such (tissue-resident memory B cells, plasmablasts, and plasma cells), leading to the establishment of IgA-secreting cells in the lung (not seen when the same vaccine was delivered intramuscularly or intraperitoneally). Finally, local IgA secretion was observed to provide superior protection to circulating antibodies alone when experiencing a secondary challenge, whether that be the same strain of flu (that the vaccine was designed to target) or another strain.
In summary, our data demonstrate that IgA-producing cells form in the lung after intranasal immunization and contribute to protection against challenge with homologous and heterologous influenza virus infection. Insights gained from our current study may be useful in designing new vaccines against other respiratory virus infections.
DOI: 10.1126/sciimmunol.abj5129.
See also earlier
post #1418.
Note: it is worth mentioning that oral vaccination also
has the potential to induce a significant mucosal IgA response. I count at least three oral and five intranasal COVID-19 vaccine candidates under evaluation.
TL;DR:
Intranasal (and perhaps oral) vaccines may promote an immune response capable of significantly reducing infection and thus transmission.
www.reuters.com
.
