UKH

If I’m vaccinated and am then exposed to delta, but don’t get a detectable infection, do I gain some broader spectrum immunity through this exposure? Genuinely have no idea.. 

if this were the case it could mean vaccine escape is less likely as we all get our immunity updated through exposure to new variants which are different but not different enough in themselves to cause infection in the vaccinated population..

just a pondering!

I have also pondered this. Also got no idea. Since we now have rising case rates again, there is every chance we might get to find out soon!

Response of a lay person who is developing a rapid awe of immunology as a field within the life sciences...

It seems like the antibodies formed against the receptor binding domain are the hardest hit by variations like delta, so neutralising immunity is more compromised than the broader spectrum that lies behind it, so I think the virus is more likely to go in then get its ass kicked, rather than being left at the door by the bouncers.  

The billion dollar question.

The immunity generated by a live infection will be against multiple viral proteins, not just the spike, especially with all that de-novo synthesis going on.  The RBD on the spike seems like a hotbed of variation; given the leaps in R0 with variants it feels like the "rapid host adaption" phase of the virus to me, perhaps cranked up by emergent selective pressures.  The capsid and membrane proteins perhaps don't have the same adaption based selective pressures as the spike, and do elicit T-cell responses.  Some suggestions the M protein may support a neutralising response - having two parallel neutralising responses starts to vanish the probability of an escape variation - https://www.nature.com/articles/s41392-020-00352-y

Feels to me like that broader response is a key part of the way out.   Immunisation based on a significant amount of neutralising immunity against a single protein is a stepping stone.  It'd be nice if some vaccines were on the way targeting a couple of the other proteins, perhaps Novavax style - as these could ease that process for the more vulnerable.

I’m curious as to why you used R0 (basic reproduction number). As 86% now have antibodies, aren’t we well into R (effective reproduction number ) territory?

I'm wondering if the proposed booster vaccination in the Autumn will go down the route of using a different vaccine to the one an individual has already had two off. I know the study involving different vaccine types is underway but I've heard nothing about the practical rollout of any booster.

With the uncertainty around how long immunity might last for the vaccinated there's now the worry that the older age groups could be vulnerable. It seems a long since we did them.

Thanks to yourself and other posters. There's been some very interesting stuff on here. 👍🏻

Yes, I think the key is that a real infection exposes the already-primed immune response not only to a circulating S-protein boost (as opposed to the pseudoinfected cells that result from the RNA vaccination) which gives the B-cell/antibody response a prod, but also, as you say, provides a new primary challenge with all the other viral proteins, not included in the vaccine, presented both by infected cells (so MHC Cl1 => cytotoxic CD8+ T-cells) and as circulating viral proteins (MHC Cl2 => CD4+ helper T-cells).

Also, a challenge with new viral variants with an S-protein with some identical, some related (overlapping) and some perhaps entirely new epitopes to those expressed by the vaccine allows affinity maturation (the really clever bit)  of the response to fine tune to select both T-cells and B-cells that bind the new epitopes even better than before.  Once the immune response has a general feel for the target it can tighten its focus on the best targets in each new variant it encounters.  

I was talking about the changes to the virus over the pandemic, and R0 is one of the measurable signs of those changes.  I wasn't applying it to the spread of cases in our situation as-is.  The significant increases to R0 suggest to me that the changes happening at the RBD on the spike protein are the obvious result of the ongoing optimisation algorithms nature is applying to the protein to adapt it to humans.  This is the part of the protein that initiates contact with a human cell, so it's easy to see why it's ready for adaption following a jump to a new host, and to see how it presents the most powerful targets for neutralising antibodies - if an antibody binds to the RBD on a spike protein with more affinity than the RBD to a human cell, that spike protein becomes disarmed and useless.  

For sure, although that 86% includes a large proportion who will no longer have such good neutralising antibodies against the India variant and subsequent downstream variants.  They'll have suffered less reduction in protection from severe disease, hopefully.  

Every day is a school day.  The things people might be able to engineer one day when all of this is fully understood...

The key question that - to my best knowledge - no one can answer as yet is to what extent coronavirus immune suppression / evasion mechanisms are still functional in a partially immune, single vaccinated host.

In a bit of good news, for the alternative order of events a manuscript preview in the current online issue of Nature suggests that an mRNA vaccine will induce a strong germinal centre reaction (indicative of long term B cell memory formation) also in patients that have recovered from a SARS-CoV2 infection.

CB

Given that a double vaccinated person can still catch Covid and then infect somebody else what vaccine uptake is necessary for herd immunity? 

Obviously vaccination is highly protective against serious illness and death for the individual but it doesn't eliminate risks of infection or passing on the infection.

This all sounds on the relatively encouraging side of the equation. As you may have guessed the scenario in my OP has occurred in our house, with our 6yo bringing covid home from school to us (both NHS staff, Pfizered back in January and April)

Fingers crossed for all in the minimike household.  I hope Jr its to have their last days in their year at school, and who knows - perhaps your exposure will turn out to be a net benefit...

I was pondering young children and this virus earlier; the majority (almost entirety?) of the clobbering effects of this virus seem to be caused by every major protein within it being entirely alien to the immune systems of all but a few SARS-nCov-1 and MERS-nCov survivors, and the concomitant immune dysregulation, which becomes ever worse with age.

In my noddy mental picture, immune dysregulation isn't an issue for children, because it can't be, because they're being exposed to everything for the first time.

So, does this mean that the immune system reconfigures itself progressively with age following the assumption that ever fewer viral proteins are unknown to a given instance (person) of the immune system as it ages, and trade-offs are progressively made on the usually fair assumption that they'll be seeing a virus for the nth time (n>>1) than the 1st time?

Could such a shift in immune configuration be another mechanism of ageing separate to its gradual degradation?  Or have I Dunning-Kruger'ed myself well beyond the supportable?

thanks, hope so.. we’re all fine (if cooped up!)

To respond to this with an opinion would only serve to prove D-K right once again..!

this looks encouraging for cross variant T cell mediated immunity and may explain  the observation that delta cases are taking off but severe disease isn’t. Let’s hope it continues.

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00204-4