UCSF team has engineered a tiny antibody capable of neutralizing the coronavirus | Hacker News Reader

UCSF team has engineered a tiny antibody capable of neutralizing the coronavirus

ucsf.edu

215 pointspfd198634 comments

Nanobodies have been around for decades, and there are reasons why they're not part of any drugs - half life is bonkers terrible (months for regular mammalian antibodies vs. hours) + non zero risk of immune reactions towards these foreign (to our genome) proteins. Source: PhD (partly) in antibody engineering

I came here to same more or less the same thing. They are, however (potentially) a good analytical tool.

Also probably a good imaging agent, but then that's like the consolation prize for every "promising" targeting approach who's "only" flaw is a shitty half life, so no end to competition!

It does say in the article it could be a helpful treatment for people who have tested positive for covid. Do you think that's just hype, or could it actually be helpful?

Seems boilerplate "could be helpful to cure xxx" statements written in press releases and grants for most research findings; neutralizing antibodies do seem to help in mitigating worse outcomes (among others Lily sells a concoction) but even when they have good half lives it looks like the neutralizers don't do too much; there's no benefit I can see for something with orders of magnitude lower half life still.

“Could be” in this context is more like “hasn’t been conclusively proven impossible”. Unless somebody is taking about human trials it is exploratory and not worth getting anybody’s hopes up unless your hopes involve grant money and publishing papers.

Mostly hype.

Absolutely right, Pfizer has failed on those as drug candidates for the last 20 years.

This is cheaper to produce and can be take more regularly than monoclonal antibodies. The more options the better!

The only places where short half life proteins have been useful is if you're delivering toxic substances and you don't want any off target effects (see BiTes - https://en.m.wikipedia.org/wiki/Bi-specific_T-cell_engager ) the technology behind the targeted becomes less relevant if you don't care about the half life. You can make antibody fragments that are only slightly larger that are still fine.

> and there are reasons why they're not part of any drugs

Caplacizumab (Cablivi®) is a Nanobody (2 VH units linked together) approved by the EMA since 2018 (and by the FDA since 2019).

One example of a very new drug; do you have any others? Any studies on its efficacy and side effects?

It’s a bit unfair to ask the parent to do this legwork. The fact that it got approved implies that it is effective and that side effects are rare and/or relatively minor.

Edit:

From the phase II trial:

“ Adverse events overall were similar between groups, with the exception of bleeding, which occurred more often with the immunoglobulin treatment (54% versus 38%). The two participants who died were both in the placebo group.” https://www.medpagetoday.com/Cardiology/VenousThrombosis/561...

Mind you this is used for TTP and thrombosis, where short lifetime is a benefit. You want to remove the clotting factor now, not forever. (We have drugs for that too.)

Short lifetime can be a benefit for anti-Covid medication too. An antibody could cross react with a vaccine and hamper the immune system response, preventing it from launching a proper reaction and creating proper immunity. You don't want the person having to wait for weeks while being vulnerable until they can get a vaccine after a successful therapy with antibodies.

But of course, distribution is a headache.

A person having an an immune system that can be vaccinated with traditional vaccines (including mRNA), while not developing meaningful resistance (such that a second infection isn't serious even if possible) from an infection where they needed antibodies, doesn't seem very likely. And if they were treated with antibodies once, they could probably just use them again, so it doesn't seem important.

Nevertheless, it would still be moderately impractical in the sense that a vaccination immunity should (probably?¹) be more effective than immunity after an infection, but it may not properly develop until the vaccine is administered without (much) antibodies present.

¹ is there any evidence or a sound supported theory that a coronavirus vaccine is more effective and/or long lasting than immunity after an infection?

Touche, there do seem to be approvals. I'll edit my post.

isn't the point to reduce severity... in icu with ventilator vs little cough? if viral load annihilated the immune response would be light and less damage to organs.

Great overview of the biotech behind these COVID-19 nanobodies by Vincent Racaniello [1]:

> Human monoclonal antibodies that block infection with SARS-CoV-2 are being used to treat COVID-19 patients, but an alternative, antibodies produced in camelids (alpacas and llamas) might have advantages. Camelid monoclonal antibodies can be more cheaply produced in mass quantities in bacteria, and protein engineering can be quickly used to produce a better therapeutic product.

Nanobodies are small and stable enough to be delivered as a nasal spray unlike the current mabs (Regeneron and Eli Lilly) that are delivered intravenously.

The paper An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike [2] was discussed in the podcast TWiV 708: Alpaca llama full of nanobodies [3] on Jan 7th.

Unfortunately this spray is too late to impact the course of the current pandemic but it gives hope for the future.

[1] https://www.virology.ws/2021/01/14/camelids-for-covid/

[2] https://science.sciencemag.org/content/370/6523/1473

[3] https://www.microbe.tv/twiv/twiv-708/

A question for people familiar with the science:

How do we build confidence that there aren't any adverse effects from protein? My intuition tells me that this stuff is so small and the world of biochemistry is so complex that who knows what can happen.

could this be used for rapid testing? Even if it's not safe for in the body use it seems like there's other ways that this could be used.

There are other antibody treatments but problem with all is time to market. Medical use approval requires trials. Trials need money.

Did anyone else read the headline here on HN, then look to the right at the parentheses that says "ucsf.edu" as the source, then think to themselves "press release from university PR department", get a bit suspicious, then decide not to click on the article and move on with their evening?

I'm not hating, exactly -- universities do cool stuff often, and I like to hear about it. But when the source is the university itself it seems a bit like COI.

(And lo, ramraj07 and others' comments bear this out: not much to see here.)

Edit: after some backlash, let me clarify: I'm asking whether others look askance at university press releases. In my experience, they're often as fluffy as press releases from corporations and the like, which was a letdown early on for me. Does this anecdote align with anyone else's experience?

feel free to dig up the Science paper then and read it

Weird how you ended up in this comment section despite "moving on".

In a modern web browser, you can do both simultaneously with ctrl-t.

Jokes aside, I was curious if anyone else furrowed their brow at university press offices. So here I am.

I do the same thing, but will often check the top comment(s) to make sure I'm not missing something and generally keep my BS detector well trained.

In this case the top comment happens to reinforce said detector.

Honestly, you rarely have to look as far as the URL; the headline itself's often enough. High on impact or even just zeitgeist + low on specificity + no quantitative statements is a great recipe for "not worth your time".

You are spot on. Universities PR scientific releases like this are usually bad. And I'd dare say, detrimental to science if it reaches the public. It sets false expectations regarding scientific work and its meaning.

Concur. As a non-scientist science-aware layperson who has had excellent experiences with UCSF and trusts them very highly, the byline definitely caught my eye. But the headline seemed overstated, so I clicked through to the comments here first, and my suspicions were confirmed.

UCSF, if you’re seeing this, I’m providing a single data point: You have diminished your credibility one quantum with one moderately scientifically-literate member of the public.

the fact that you are facing backlash for calling our University Corporatism is ridiculous. No one should be above scrutiny or questions... Thats Science 101

Having seen the horrible things my university's press department was able to do with my work when i was in academia... I'm not really inclined to get all hyped up over articles such as these.

To their credit though, they don't claim that the antibody is using artificial intelligence, or AI, to do it's thing.

Another sign that it’s a puff piece is when it starts describing the persons involved: X grew up in place Y, etc etc.

Indeed, I have noticed this trend with "news" more and more. The style is characterized as being written like a non-fiction novel. I wish news was just more concise and to the point. I don't have time to read thru the fluff.

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