COVID-19 , immunity

[JJackson]

gs I do not think there is a list of the type you want but the antigenic sites and the mAbs that react with them in the table in post #9 were selected because these are the serum antibodies that are most common. There are 12 in the table which would be a good start to your list. The IgG is about 150kDa where as the Spike is nearer 800kDa and, as it is a glycoprotein, you would need to add the weight of the glycans (just to get a sense of scale). I do not know if it will form clumps with SARS-CoV-2, as you would see in a agglutination assay, where the two branches of the IgG bind to spikes on two virions which then clump with others using more IgG bridges until you get a raft in which none of the virions able to infect a cell. The exposed Fc portion of the antibody will also bind other immune cell receptors which can then induce clumping by a similar bridging mechanism. This is not an uncommon mechanism.

 

[Emily]

You have a wealth of information about the immune system organized here. Even though I don't grasp this as well as you, my sense is that you are right about the variant threat - there isn't a biological basis for fear at this point.
I don't fear a threat from other species as intermediates. I would think that if a human origin virus adapts to another species, it would lose its ability to spread easily among humans. That seems to be the usual pattern with farmers getting swine flu's. It is a risk we take to benefit financially or socially from relationships with other animal species.
Chinese scientists are doing some cruel experiments with dogs and flu, justifying this by claiming dogs might be mixing vessels.

 

[Vibrant62]

Interestingly, a few new papers that expand on the potential risks here. I would suggest a MERS vaccination for camels asap would be prudent. Cats would seem to be less of a problem for us than we are to them.

1.https://www.atlantis-press.com/journals/jegh/125946349
2.https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab104/6144906
3.https://www.jbc.org/article/S0021-9258(21)00208-8/fulltext

 

[gsgs]

concerning the waning effecitveness of the current COVID-vaccines,
I found this nice review published 2021-04-01: (see p.12)
https://pubs.acs.org/doi/pdf/10.1021/acsnano.1c01845
(after checking keywords wane,waning in the first 20 out of 172 papers at google-scholar
found by keywords
waning covid vaccine novavax moderna mrna adenovirus

cited by 6 :
https://scholar.google.de/scholar?ci...iodt=0,5&hl=de

Nano-Enabled COVID-19 Vaccines: Meeting the Challenges of Durable Antibody Plus Cellular Immunity and Immune Escape
André E. Nel* and Jeff F. Miller
--------------------------------------

The neutralizing antibody response to seasonal
(“cold”) coronaviruses is of transient duration, allowing the
occurrence of reinfections.[33] In contrast, the protective
antibody responses to SARS-CoV-1 and MERS lasted a
minimum of 2−3 years after recovery.

...half-life of anti-RBD antibody decline to be ∼36 days;135

...people with milder infections generate lower antibody titers
that decline more rapidly.[138]

... 8 months {followup study}.139

{ neutralizing IgG antibody titers against the
spike protein and RBD remained relatively stable, with only a
modest decline over 6−8 months }

memory CD4+ and CD8+T-cells {have} half-lives of 3−5 months.

The decay kinetics of memory T-cell responses after
COVID-19 are similar to the vaccination response to the
yellow fever virus, which is known to confer long-lasting
immunity.[29]

there is a critical requirement for TFH
cooperation with germinal center B-cells in the development
of durable immunity to polio, smallpox, and other

a promising approach for augmenting memory B-cell
responses in COVID-19 could be to develop vaccinating
nanoparticles ...

 

[JJackson]

There is a lot being written about the Omicron variant attempting to explain how it is impacting immunity and, in the interest of keeping it simple and understandable, much is being lost.

The aim of this post is to look at the interaction of the virus and host’s immune system to try and reach a more nuanced understanding of what is likely to be going on.

Natural infection will produce a very broad range of B and T cell responses but in a rather scatter gun manner. The vaccines, with the exception of one from China, only target the spike protein which concentrates all its effort on the most useful antigenic sites capable of making neutralising antibodies which can block infection. This comes at the expense of ignoring 90% of the genome. The vaccines were developed to limit severity and deaths in the hope that at least one of them would be able to do so by at least 50%. They have wildly exceeded expectations with several exceeding 70% and some into the 90s. As an ancillary benefit they happen to have also cut infections by about 50%, which was not by design and was not anticipated. They are given intramuscularly, which is good for IgG production, these circulate in the blood which gets them all over the body. The primary site of infection in the nasal cavity where, dimeric IgA is the primary source of infection control, and these will be produced after the infection starts - which is why the vaccines are better at stopping severe disease than infection. The initial infection then spreads into the lungs which is where the damage is done requiring oxygen support and hospitalisation. Any reduction of viral load at infection, or slowing of subsequent spread, buys time for the immune response to ramp up and clear the virus.

In Omicron’s case there are 36 changes in the spike protein sequence which will inevitably change the structure of the spike trimer. The antibodies, matched to the earlier variants, will bind more weakly and neutralisation assays to sera from previously infected or vaccinated hosts are showing this. Early data is also showing that the combination of prior infection with vaccination is giving better neutralisation than two vaccine doses. There are two probable reasons for this firstly those vaccinated do not have the backup of antibodies, or T cells, to all the non-spike proteins. Secondly the vaccine will only produce antibodies to the spike antigenic sites found on the protein included in the vaccine. In a natural infection the virus operates as a quasi-species, with many different variants produced in the course of the infection, and the immune response will be to all of these. This increases the chance that at least some of the B and T cells will start off as better matches to Omicron’s structure. Regardless of how good the initial match is the immune system will start amending its immune cell mix to match the current infection by the process of hyper mutation in the germinal centres (which I looked at in an earlier post in this thread). Again it is all to do with how much whatever you start with can buy time for the immune system to get a well matched response. Patients who have a condition that stops them making B cells, which make the IgG antibodies, do surprisingly well.

The next thing to consider are the tests and correlates of protection. A correlate of protection is something that you can measure that tells you how well you are protected but at present we have none. The easiest thing to measure is IgG blood levels and there are plenty of tests for these but there is no clear way of interpreting them. Even if you measure neutralising antibodies it is of limited use as it is only one part of the immune response and not necessarily the most important. CD8 T cells, which can directly kill infected cells, are far more difficult to measure. There is also ADCC a process in which IgG, to any peptide from any viral protein, that is bound to the cells MHC receptors can cause NK cells to kill that cell. In a similar manner the complement cascade can puncture the cell membrane and induce apoptosis. All of these are part of the adaptive immune response and the efficiency on the innate response also needs to be allowed for.

The rapid antigen lateral flow test usually target the N protein which has 3 changes and 3 deletions and does not seem to have been compromised. The PCR tests normally use 3 primers only one of which targets a section of the spike sequence and this is causing a lower response (an S drop-out) but the other two work and it is reasonably simple to change the S primer so it works. The only practical effect is when the S drop-out is detected that sample is more likely to be selected for full sequencing which will give a false impression of how quickly Omicron is supplanting Delta. Covariants.org show the relative frequency of each variant by country in two week blocks based on GISAID submissions and is showing 100% Omicron in South Korea. A closer look shows it is based on one sequence, South Africa is 83% on 476 submissions but due to the S drop-out this is probably an over estimation. The best country to get data from will be the UK as it has the highest full sequencing rate typically submitting 100,000 in the same time period. The problem is they also have a very high vaccination rate and the highest rate of infected per head of population for countries over 20m. Under these conditions Omicron will have a big advantage over more ‘standard’ variants so, while accurate, may be a poor guide to relative fitness in other populations.
There has been speculation that virulence may be reduced but this is premature. For any reliable data we need to wait at least a month from the time there is a significant number of infections in any given population. We also need this from both a country like the UK and from an area with both low vaccination and previous infection rates.

There is a lot to consider and a lot I have left out.

 

[sharon sanders]

bump this

 

[JJackson]

This post is just to provide two links to episodes of Immune which are excellent and helpful in understanding B cells and their maturation.
If you are not very familiar with this topic it may be helpful to read post #14 in this thread first.
Immune 52: B cell boot camp with Gabriel Victora

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Immune 74: Germinal center dynamics with Carla Nowosad

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