This is a conversation with an MD I recorded which may answer some of the reluctance:
tldr; An untested delivery mode scares an MD to think that neurodegenerative diseases will increase in vaccinated.
I think lipid nanoparticles may have too broad a tropism, far broader even than attenuated virus vaccines (which are still limited to the tropism of the wild-type virus), and thus could pose a uniquely high safety hazard due to cytotoxic attack on the broad cellular range that uptakes the LNPs. Since the LNPs would enter cells via endocytosis, the SARS-CoV-2 epitopes would be expressed on MHC-1 molecules, making them targets of cytotoxic CD8 lymphocytes, attacking a much greater range of cells than any previous vaccine modality. This is concerning in general, but it’s a nightmare scenario if the vaccines are crossing the blood-brain barrier and endocytosing into e.g. oligodendrocytes (multiple sclerosis risk) or motor neurons (which could possibly cause an ALS-type picture). No other vaccine has this broad tropism. That is THE major safety concern here.
1. Because of the anatomy and circulatory trajectory from the deltoid and cephalic vein (essentially a straight shot into the SVC), if enough “spillover LNPs” are getting shuttled into the right atrium and transiting through the pulmonary circulation — which could be high, another reference here for the rich vasculature around IM injection — then one of their earliest stops on the map after exiting the heart would be in tissues serviced by branches of the common carotid and subclavian arteries (including the CNS), enhancing delivery to tissues behind the blood-brain barrier simply due to higher relative concentration at tissue corridors more proximal to the injection site. 2. Even if initial transit through the BBB and into other sensitive tissue parenchyma is relatively low, there’d be a cumulative effect with each booster delivering more spillover LNPs to those non-local sites. 3. Related to that point, the duration of immunity is still unclear, and there seems to be general agreement that while COVID-19 symptoms are reduced with the immunization, viral spread is not. If antibody and memory B/T-cell levels wane within a few months after vaccination, then we’d be looking at repeated boosters possibly multiple times a year given ongoing community dissemination. And since the development of many e.g. CNS disorders is gradual — with subclinical issues taking shape over years before clinical manifestations become apparent (as seen in MS and ALS) — such cumulative damage likely wouldn’t raise red flags at first, but could increase in likelihood with successive boosters.
This is a conversation with an MD I recorded which may answer some of the reluctance:
tldr; An untested delivery mode scares an MD to think that neurodegenerative diseases will increase in vaccinated.
I think lipid nanoparticles may have too broad a tropism, far broader even than attenuated virus vaccines (which are still limited to the tropism of the wild-type virus), and thus could pose a uniquely high safety hazard due to cytotoxic attack on the broad cellular range that uptakes the LNPs. Since the LNPs would enter cells via endocytosis, the SARS-CoV-2 epitopes would be expressed on MHC-1 molecules, making them targets of cytotoxic CD8 lymphocytes, attacking a much greater range of cells than any previous vaccine modality. This is concerning in general, but it’s a nightmare scenario if the vaccines are crossing the blood-brain barrier and endocytosing into e.g. oligodendrocytes (multiple sclerosis risk) or motor neurons (which could possibly cause an ALS-type picture). No other vaccine has this broad tropism. That is THE major safety concern here.
1. Because of the anatomy and circulatory trajectory from the deltoid and cephalic vein (essentially a straight shot into the SVC), if enough “spillover LNPs” are getting shuttled into the right atrium and transiting through the pulmonary circulation — which could be high, another reference here for the rich vasculature around IM injection — then one of their earliest stops on the map after exiting the heart would be in tissues serviced by branches of the common carotid and subclavian arteries (including the CNS), enhancing delivery to tissues behind the blood-brain barrier simply due to higher relative concentration at tissue corridors more proximal to the injection site.
2. Even if initial transit through the BBB and into other sensitive tissue parenchyma is relatively low, there’d be a cumulative effect with each booster delivering more spillover LNPs to those non-local sites.
3. Related to that point, the duration of immunity is still unclear, and there seems to be general agreement that while COVID-19 symptoms are reduced with the immunization, viral spread is not. If antibody and memory B/T-cell levels wane within a few months after vaccination, then we’d be looking at repeated boosters possibly multiple times a year given ongoing community dissemination. And since the development of many e.g. CNS disorders is gradual — with subclinical issues taking shape over years before clinical manifestations become apparent (as seen in MS and ALS) — such cumulative damage likely wouldn’t raise red flags at first, but could increase in likelihood with successive boosters.