variant specific boosters fail to elicit variant specific response

did NIH researchers just prove the moderna vaccine leads to OAS?

THIS is a very interesting paper written by a bewilderingly large number of authors (66 in total), many from NIH and NIAID. it carries the somewhat technical and tepid title of:

it would, frankly, be quite easy to miss or dismiss as “oh, it’s just an equivalency study.” but this has some real juicy bits that were brought to my attention by long-term gatopal™ and all around good guy and standout bright spot at brown university medical school andrew bostom with whom i have had the good fortune to collaborate on a number of projects.

the researchers took a number of non human primates (NHP’s) and vaccinated them against covid using mRNA-1273 (the moderna vaccine).

they observed the now well known immunity fade out to 40 weeks, then boosted them in week 41 with either another dose of mRNA-1273 or with a variant specific dose called mRNA-Omicon that used the spike protein from the Omicron variant instead of the original.

the question was simple:

and so was the answer.

they worked out to be very much the same, so there was no benefit to a variant boost vs more of the old one. lots of studies cited to claim boosters are good (albeit far less so vs omicron and with rapid fade, counting only those doses +2 weeks for efficacy and ignoring/misallocating the immune suppression window) yadda yadda. so far, so boring.

but then it starts to get interesting because of what they may have accidentally proven (or deliberately investigated and then buried in technical reporting far away from the headlines). they found original antigenic sin (OAS, also known as hoskin’s effect).

well, NOW i’m interested.

it’s easy to miss the significance here if you’re not familiar with what you are looking at. what they are saying is that exposing you to the spike/s-1 proteins of omicron elicited no immune responses that diverged from the previous vaccine.

assuming (and i think this is likely a good assumption) that this vaccine accurately modeled omicron, this is a sign of antigenic fixation. you have locked your immune system into one set of responses and it is not learning new ones when faced with novel pathogen variants. (read OAS link above for details on how this works)

we can see the issue here:

this is a scatter of memory B cell specificities post immunization and boosting. think of B cells as a recipe storage medium. they are not the antibodies, they are the cells that remember which antibodies to make and how to make them. it’s your immune memory.

these charts are a little tricky to read, so let’s walk through them:

the scatters break into 4 quadrants. upper left are B cells specific to the Y axis variant. lower right are B cells specific to the X axis variant. the upper right are effective on both.

look what happens here. you can see fade from week 6 to week 41 and then a resurgence in week 43 (post a week 41 boost)

now look at how different the responses to omi are vs traditional 1273.

not only is the response more muted, it’s FAR less broad. you’re getting far less B cell variety from the variant based booster, but more tellingly, it’s ALL a subset of the 1273 boost’s elicitations.

there is nothing new.

a new pathogen with more than 30 mutations on the S protein evoked NO new immune response. that is, to say the least, VERY suggestive. one might even go so far as to call it “outright worrying.”

it means your immune response has ceased to be trainable.

and this means you can get trapped, like this, in a suboptimal and increasingly ineffective immune response.

worse, it means that this response becomes a primary evolutionary selector for the virus. variants able to evade immunity without triggering a new adaptation will be selected for. rapidly. it’s not chance outcome that omicron was an OAS variant. it was the near inevitable outcomes of the selection pressure of antigenic fixation. (interestingly, omi looks to be a long throwback. it did not evolve from delta. it diverged from old strains before there even WAS a delta. this supports the idea that it was just a failed minor mutation until vaccines changed the playing field.)

this is a predicted and predictable outcome from leaky vaccines. (and one we’re seeing validated in UK data)

it’s actually WHY we don’t use leaky vaccines.

now, what would have been REALLY interesting is to do this same study but use actual omicron virus instead of boosters and to then compare the B cell map in vaccinated primates vs those who were vaccine naïve.

if the latter showed broader and more varied B cells, you’d know for sure you were dealing with an antigenically fixated population whose future immune development will be locked in place by overly narrow vaccines. this could, quite possibly, prevent long term sterilizing immunity from EVER developing in the vaccinated precisely BECAUSE they were vaccinated.

we’ve seen this in N antibodies already.

testing the effects of adaptive immune learning from exposure to live pathogen is a really obvious next step in an experimental series like this and one the researchers were well set up to undertake.

i wonder why they didn’t…?