immunologically speaking, there no rhyme or reason to believe that if 2-dose vaccine-induced neut Abs hang around for 6 months, somehow they will hang around much longer after 3rd dose. 1/
in general, it is quite unexpected that after such robust 2-dose antigen priming, as mRNA vaccine does (based on Ab titers immediately after 2nd dose), we should see such a precipitous drop in vaccine efficacy within 6 months. 2/
everyone pays attention to neut Ab titers but even NIH/Moderna's own study in lab mice showed neut Abs are not essential at all. These were confirmed in a more recent study using B cell KO mice. No Ab is needed to protect mice against #SARSCoV2.
3/
3/
some now argue, hey, other vaccines are 3-dose vaccines too. Wait a minute, do they realize that only now? where were the same people in December 2020? I did not recall anyone saying, we need a 3-dose vaccine, not 2-dose. 4/
sure, many vaccines are 3-dose vaccines at 0, 1 month, and 6 months time. But everyone knows that but for some reason, no one even suggested running a trial for such an obvious thing. if @pfizer and @moderna_tx knew about 3-dose why not set up exactly that? 5/
I assume the 2-dose schedule came about based on neut Ab titers in initial trials. Titers were so high (compared to what we have seen in other conventional vaccines, mostly inactivated) that naturally, they thought 2-dose will be enough. 6/
sky-high Ab titers don't materialize out of blue. It needs CD4+ T cells. So, 2-dose gives a good T cell priming too. This is a reason why it is so unexpected what we are observing. 3 or 4-dose vaccine is needed to build up neut Ab titers but we got that and plus with 2-doses
7/
7/
it is true that lab mouse is not an ideal model for the human immune system. For example, in mice, neut Ab titer stays steady after mRNA vaccination, but not in humans. 8/
the closest thing I have seen in immunology that resembles the mRNA vaccine effect is a super-antigen injection that activates specific B/T cells to such a degree that it exhausts them and they disappear leading to some kind of temporal unresponsiveness
9/
9/
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