Human Antibodies Target Many Parts of Coronavirus Spike Protein

https://directorsblog.nih.gov/2021/05/18/human-antibodies-target-many-parts-of-coronavirus-spike-protein/

by danboarder • 5 years ago

61 23 5 years ago

directorsblog.nih.gov

No way, is this new research? I thought antibodies (or maybe HN taught me) were suuuper specific to a certain part of the protein.

maxerickson• 5 years ago

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

wombatpm• 5 years ago

Developing and isolating monoclonal antibodies against a single protein was a major advance. And even those have multiple binding sites

chaimanmeow• 5 years ago

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...

kevin_b_er2• 5 years ago

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.

tootie• 5 years ago

Most of this goes over my head but it seems that the silver lining of this pandemic is absolutely bounty of new discoveries about virii and immune responses.

decker• 5 years ago

It's quite amazing how the human body has defense in depth to mitigate changes in protein shape due to mutations.

planet-and-halo• 5 years ago

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

gopalv• 5 years ago

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

mrkramer• 5 years ago

Human body is miraculous creation a true biomachine.

throwawayboise• 5 years ago

Are these multi-target antibodies only produced by natural infection, or also by the vaccines? Didn't seem to be mentioned in the article.

SiebenHeaven• 5 years ago

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

kevin_b_er2• 5 years ago

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?

tzs• 5 years ago

BNT162b2 is the one everyone knows now because it was the one picked for phase 3 trials, and it uses the full spike.

Same with the Moderna vaccine [1].

[1] https://investors.modernatx.com/news-releases/news-release-d...

answer42rgb• 5 years ago

Natural immunity is more robust than vaccine immunity. Not at all surprising. Why aren't we testing people for covid antibodies before injecting them with experimental medicine from corporations with a history of ethical abuses which were granted immunity from any liability their gene therapy may cause?

legobmw99• 5 years ago

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.

Something1234• 5 years ago

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.

juanani• 5 years ago

I'd argue that the billions already sunk are a great incentive to keep the publishings to a minimum, but I'm just a crackpot so nvm..

astrange• 5 years ago

He is wrong. Vaccine immunity is usually stronger than natural immunity; that's what "adjuvants" are for.

For COVID, there's multiple vaccines, some of which include the spike and some include the whole thing. The most effective ones only include the spike, although of course that doesn't mean it's ideal.

RiverStone• 5 years ago

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.

jcims• 5 years ago

Not sure if everyone is aware how large these molecules are. According to this paper [1] the molecular mass of the spike (S) protein for SARS-CoV-2 is between 180 and 200 kilodaltons.

A dalton is formally 1/12th the mass of a carbon-12 atom, or roughly the same as the atomic mass unit I learned about in high school chemistry.

So the molecular weight or mass of the spike protein is approximately 180,000 to 200,000 atomic mass units! That seems huge to me.

1 - https://www.nature.com/articles/s41401-020-0485-4

rolph• 5 years ago

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

gilleain• 5 years ago

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

Human Antibodies Target Many Parts of Coronavirus Spike Protein

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