Human Antibodies Target Many Parts of Coronavirus Spike Protein

also worthy of note is this exists naturally as a trimeric complex of three such spike molecules

It might be easier to think about these numbers if you know that the average mass of an amino acid is 110 daltons. So 180 kda is around 1,600 residues.

From this paper https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055910/

> Peptides from 10 to 30 kDa typically fold into a single domain. Peptides larger than 50 kDa typically form two or more domains that are independently folded.

So most larger proteins are formed from complexes of smaller ones. That said, there are some amazing examples, such as the proteasome, or the vault.

See https://pubs.rsc.org/en/content/articlehtml/2015/cs/c5cs0015... for more detail

It's awesome. Nature is the original distributed system.

> the human body has defense in depth

The complement system[1] is somewhat of an amazing look at how inanimate parts of our immune system are like little circuits and circuit breakers in chain reactions, completely triggered at random (i.e you need to "bump" into it, it is not an active entity).

[1] - https://en.wikipedia.org/wiki/Complement_system

Human body is miraculous creation a true biomachine.

This is the real question. Especially for vaccines that mimic the spike protein to make another attenuated virus look like a coronavirus.

Likely produced by vaccine too, at least the ones that used full-length spike protein. The rejected BioNTech candidate for example (BNT162b1) had only the RBD. BNT162b2 is the one everyone knows now because it was the one picked for phase 3 trials, and it uses the full spike. Obviously if the vaccine were the RBD-only one, there'd be no antibodies generated for NTD or S2 by the vaccine.

Here's a paper where the studied the antibodies: https://www.degruyter.com/document/doi/10.1515/cclm-2021-033... Their assays(tests) may not have been quite specific enough for these other target locations, but it appears to cause antibodies against multiple sites on the spike.

In the end, the OP article from NIH only analyzed the paper about a small set of people who recovered from infection and says nothing about analyzing vaccine recipients, because that's not what the paper was looking at.

Now what you should ask: What is the distribution of antibodies for a vaccine vs infection and what does that mean for variants. Because the paper and the article are concerned that the results of infection seem to cause a lot of anti-NTD antibodies and while they work, the NTD domain is mutating a lot in the variants of concern.

There's two lines of discussion that seem to result: 1. Is too much focus on anti-NTD from infection bad against variants long term? Is this how we're getting "reinfections" from variants? 2. Should new vaccines target certain parts that don't change like S2 to get even better and more universal vaccines against all the variants of covid19?

Each antibody is pretty specific. The immune system makes lots of different ones, even in response to a single foreign protein.

The goal here is probably more characterization than discovery. For instance, here's a higher up Google result for "antibody heterogeneity" published in 1966:

https://www.karger.com/Article/Pdf/209100

specific antibodies are.

The article tells about three different specific antibodies, targeting RBD, N-terminal domain, and S2 part of spike.

T-cells are even more amazing in the way they target portions of proteins that are vaguely similar. So you could be exposed to some pathogen A, and have T-cell immunity and recognition against some pathogen B (which is quite distinct and different from A).

https://med.stanford.edu/news/all-news/2013/02/immune-system...

Single antibody, yes. A lot of different antibodies are made. The ones that seem to act "better" get made the most.

As far as can be understood, the immune system does random self-mutation of its antibody generation and starts picking winners at local maxima.

The result is antibodies start targeting various parts of viruses, bacteria, and other invaders.

Binding and neutralizing the spike protein neutralizes the virus, so the vaccines used it. Upside: immediately effective vaccine. Downside: Its possible random antibodies in natural infection could target another critical protein to covid19 that is not on the spike, but also shuts down replication.

So that's also in the field of study for covid, as well as influenza, vaccines. Is there some part of the viruses we could target instead of the spike(or the influenza hemagglutinin) that would cause immunity against the entire class of virus? Such is the search for a universal influenza vaccine.

I think it’s too soon to say, but there seems to be substantial evidence against what you’re claiming. In fact, it may be the opposite entirely:

https://www.biorxiv.org/content/10.1101/2021.04.15.440089v2....

https://www.nejm.org/doi/full/10.1056/NEJMc2032195

To be clear: I’m not arguing your later point. The questions of oversight and liability are very important and under-discussed.

You're not wrong. It would certainly be interesting to see what kinds of antibodies everyone has but that's not feasible. There's more than one way to do it.

But you do sound like a crackpot with how many billions of dollars have gone into the research, and how few published reactions have occurred.

mRNA vaccines are not “gene therapy” in the popular sense of the term. They do not alter your genes in any way.

Calling vaccines gene therapy is like calling milk “pus” or saying you shouldn’t use a microwave because it has “radiation”.

It’s an appeal to an emotional response to a word. It’s one of the most annoying argumentative tactics.