
NIH Scientists Identify Antibody That Neutralizes Nearly All HIV Strains - jjuhl
https://www.niaid.nih.gov/news-events/nih-scientists-identify-potent-antibody-neutralizes-nearly-all-hiv-strains
======
nneonneo
I read through the original paper
([https://dx.doi.org/10.1016/j.immuni.2016.10.027](https://dx.doi.org/10.1016/j.immuni.2016.10.027),
paywalled).

In essence, an antibody called N6 was extracted from an HIV patient. The
patient is a long-term nonprogressor who has had HIV for 21 years, but an
exceptionally low viral load of <1000/mL and normal CD4 T-cell count. This
indicates that his immune system has kept the virus at bay for all these years
with essentially no ill effect.

HIV viruses have a surface protein complex called Env, which binds to the CD4
surface protein to gain entry to T-cells (part of the immune system). HIV
cannot transmit without this protein complex, and so certain parts of the
complex are very well conserved across different HIV strains.

N6 binds to this part of Env, in some sense "simulating" CD4. However, because
it's just an antibody and not a cell, once Env is bound it cannot infect
anything. This is what makes N6 a neutralizing antibody.

The thing that makes N6 special (more potent and more broadly applicable) is
that it is able to avoid the parts of Env that HIV doesn't need for
replication. Imagine Env as a wrench. The head of the wrench is a specific hex
shape to mate with CD4 and can't change. Antibodies can grab on to the wrench
handle to prevent infection. But the handle can change, and HIV regularly
mutates this part to avoid being caught - adding side branches, changing the
shape, and so forth. N6 is cleverly arranged so that it can strongly bind to
the wrench without grabbing the handle too strongly - in other words, it
tightly binds the head of the wrench like a person wrapping a thumb and index
finger around it (this hand analogy appears in the paper). The result is that
HIV has a much harder time getting out from under the antibody, since mutating
itself to alter the head shape would also affect infectivity.

Now that larger HIV screening trials are done, and the technology has advanced
to better detect such super-antibodies, more of these clever antibodies may be
discovered. We may yet have a good shot at defeating this tricky virus!

~~~
Twirrim
Just to check I understand this correctly, as a layman:

It stops HIV from progressing in the body, holding it at bay. Someone with HIV
would need to take this medicine for the rest of their lives. It doesn't
actually cure it. (not denying that holding it at bay is a _significant_ step
forward)

~~~
snowwrestler
It's an antibody, so in theory the human body can produce it itself. That's
how vaccines work: they trick your body into producing antibodies against the
real pathogens.

The question is whether all humans can produce this, or just some genotypes.
If it's the latter, then yes, some people would have to take it as medicine
and never stop.

~~~
ars
> then yes, some people would have to take it as medicine and never stop.

Which is a problem since it would probably be a monoclonal antibody and those
are the most expensive drugs to make. Like hundreds of thousands or even
millions per year expensive (depending on what dose is needed).

If it really does cost millions per year the US couldn't afford it - it would
cost over a trillion per year to treat everyone in the US, and more than 40
trillion to treat everyone (and that's just for the medicine).

(For comparison total healthcare spending in the US is 3 trillion.)

So better hope that either the price goes down, or that it only requires a
limited course of treatment. Can you imagine a cure for HIV, and we can't
afford it?

~~~
nopinsight
What are the reasons behind such prohibitive cost? Rare expertise, advanced
factories, amount of time required, lack of economy-of-scale, monopoly,
something else?

If the cure is proven, the society will likely be able to mobilize much more
resources, particularly to scale up operations.

Special expertise can be trained to other biologists (the underemployment
problem would be mitigated as well). More biologists could be trained.
Likewise for factories, materials, etc. Monopolies can be broken.

What factors cannot be scaled up with such an approach? (Honest question. I do
not know anything about antibody production.)

~~~
ars
> What are the reasons behind such prohibitive cost? Rare expertise, advanced
> factories, amount of time required, lack of economy-of-scale, monopoly,
> something else?

The first 3. Monopoly doesn't help I'm sure, but this drug class in inherently
very expensive to produce, there's a reason there is little outcry over the
prices charged.

It's extremely labor intensive, and very hard to scale up. They are also
inherently dangerous, so there is a need for extreme purity. (See:
[https://en.wikipedia.org/wiki/TGN1412](https://en.wikipedia.org/wiki/TGN1412)
for what a monoclonal antibody can do, you would not want that to happen by
accident.)

As of right now this drug class remains the most expensive of all drugs, I
would assume if it were possible to make it cheaper they would have.

But we'll only really know once the first generics enter the market.

------
jliptzin
Not my area of expertise but even if we can address 99% of strains, wouldn't
that last 1% just take over and become the new 100% leaving us back where we
started? Or is the promise here that we can combine this discovery with
another that solves that remaining 1%? Or, do the mutations of that last 1%
make HIV less virulent or harder to transmit?

~~~
orblivion
It would seem to me that this concept of the strongest strain taking over only
would happen if there were some sort of competition for resources. If you have
one strain of HIV it seems weird to think that it would stop you from getting
another strain and then passing both on. But "not my area of expertise"
either.

~~~
nonbel
First, it seems very difficult (for a virus) to transmit HIV via vaginal
intercourse[1]. Second, most infections appear to start from a single
virus,[2] despite the huge genetic diversity of intrapatient HIV that
supposedly makes it hard to treat[3]. That means most of the strains found
within one person never get transmitted. How do you manage to transmit HIV
contaminated fluids but only one infection occurs in the receiving person?
Very strange.

Another strange thing, it does not seem all that difficult (relatively) for
interspecies transmission to occur: "Scientists have now documented that the
SIV virus has jumped from monkeys or apes into humans at least 13 separate
times!"[4]

Perhaps those transmissions are due to self-injury while cutting infected
meat, etc. The vagina is tissue that _expects_ the presence of foreign human
cells, and so has defenses against them. Anal sex, injections, etc are a
different story. To me it sounds like an entire cell gets transmitted.

[1]
[http://m.jid.oxfordjournals.org/content/191/9/1403.full](http://m.jid.oxfordjournals.org/content/191/9/1403.full)

[2]
[http://www.ncbi.nlm.nih.gov/m/pubmed/18490657/](http://www.ncbi.nlm.nih.gov/m/pubmed/18490657/)

[3]
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614444/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614444/)

[4]
[http://evolution.berkeley.edu/evolibrary/news/081101_hivorig...](http://evolution.berkeley.edu/evolibrary/news/081101_hivorigins)

EDIT: Another possibility is that the vast majority of these variants found
floating free in the blood are non-functional and serve as chaff to confuse
the immune system.

------
belorn
Is this NIH scientist funded by tax money, and if so, what does that mean for
a future vaccine or drug? Will it still be patented, and if so, who will hold
the patent?

~~~
refurb
Look up the Bayh-Dole act. The researcher who receives the NIH funding is free
to patent it and sell that patent to a drug company.

~~~
mattkrause
Are you sure about that? Bayh-Dole covers inventions arising from extramural
funding (i.e., the NIH provides a grant to people who are employed elsewhere).

I'm not sure how it applies here, where ~80% of the authors appear to be
directly employed by some of the NIH's Institutes.

~~~
refurb
Oops! Didn't catch that. If they work for the NIH, then the patent would be
the NIH's.

------
ejstronge
Not my area of scientific knowledge, but this is a really exciting field!

One of the current challenges being worked on is how to train individuals to
make these complex antibodies. We've isolated these from people with long-term
exposures to HIV, showing that the body can generate these broadly
neutralizing antibodies.

Some current work is focusing on developing a series of peptides that can coax
HIV negative individuals to make these complex antibodies.

~~~
IgorPartola
Are you saying that some HIV positive individuals naturally develop these
antibodies over time, curing themselves of HIV? Or am I misreading?

~~~
dogma1138
Developing antibodies != curing themselves.

Your immune system can and does fight the HIV virus, it does loses that fight
because HIV attacks the immune system, can hide for years, and has a cell to
cell infection vector.

The immune system is also limited to what it can do, and when viruses can
spread cell to cell there isn't much it can do since there is little to no
attack surface available for the immune system to work with in that case.

Antibody and therapeutic vaccines can be used as post exposure treatments and
combined with other regiments to help slow down or even control the progress
of HIV and AIDS in already afflicted patients.

A therapeutic vaccine with a regiment of reverse-transcriptase inhibitors and
a treatment to control cell suicide upon infection can probably be developed
for HIV and for other retroviruses, well excluding the antibodies it is what
we already are doing today mostly.

~~~
rms_returns
>> and has a cell to cell infection vector.

I am an absolute noob in science, but still want to ask out of curiosity. If a
biological virus can have a cell to cell infection vector, can't an anti-body
or immunogen also have a cell-to-cell "replenishing" factor?

~~~
dogma1138
Like mentioned already by another poster antibodies are an extracellular
mechanism, they do not function within the cell.

Cell to call transfer and communication happens all the time, cells share
nutrients and many other things, some viruses take advantage of that mechanism
allowing them to basically cross cellular and tissue boundaries.

Some can exploit this to the extreme by actually replicating only parts of
themselves in each cell and using the cell to cell transfer highway to be
finally assembled in another cell, this is often used to prevent cell suicide
since one of the intracellular defense mechanism is basically the cell
invoking cell death upon detecting an infection.

If you want an analogy from the technology world think about it as staged
payloads that some malware use, each payload on it's own is undetectable and
even non-functional but when everything reaches the final target all the
payloads are assembled into the final piece of malware that takes over the
targeted host ;)

~~~
eecc
That's fascinating. Are you just speculating or is there some paperwork
describing these findings?

~~~
dogma1138
Speculating about what?

If you are interested in cell to cell infections NIH has an article about it

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587356/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587356/)

There are quite a few other sources on Google, overall viruses are pretty
sneaky, some of them even ask the cell politely to establish new cell to cell
contacts to facilitate cell to cell infection.

You might also like to look up virus assembly and budding, since it's also a
pretty interesting topic, you might have viruses that do cell to cell
infection of their naked forms then the final polymerization of their shells
happens in another cell and they might even do the final budding in another.

Expect nightmares tho ;)

P.S.

Cell to cell transfers might also be called exocytosis (sometimes also called
reversed endocytosis) (exit) and endocytosis (entry) so if you are googling
and can't find what you need might need to use the scientific terms.

------
grogenaut
So in a case like this does the patient own any patentability of their own
antibodies? Or did they sign it away in treatment/study?

~~~
Hondor
Patents are to incentivise inventions. If an HIV patient could patent their
antibodies, that would limit their usefulness while also giving no incentive
to anyone to invent better ones, since you can't invent them - just wait and
hope if they appear. So I certainly hope they can't do that.

Rather, it's the researchers who went looking for them who should be granted
any patent rights. They're the ones who could work harder to produce better
results and can have their performance improved with more rewards like a
patent's monopoly.

------
koolba
Would this type of research lead towards a solution that is preventive (e.g. a
vaccine) or something that would treat existing cases?

~~~
akiselev
I'm not an expert in vaccine development but I believe this _could_ lead to a
preventative treatment. Unfortunately, the treatment would probably be very
dangerous because unlike smallpox or polio, the human body can't effectively
fight HIV and an acute infection almost always turns into a chronic one. If a
patient's immune system fails to attack a weakened smallpox strain (the
vaccine) and it turns into an acute infection, the risk of life altering side
effects is minuscule and more often than not, your immune system will fight
off the infection. HIV is different because its only real effect on the body
is the destruction of T-cells, which the virus uses to reproduce, and there is
no stopping that process only slowing it down. If you take an HIV vaccine
developed with this antibody and your immune system fails to learn it (or the
strain mutates before it has a chance to, which is a remote but very real
possibility with retroviruses), you will eventually develop AIDS or spend a
lifetime taking expensive drug cocktails with a long list of serious side
effects.

There are tricks to developing vaccines without using the pathogen directly,
like constructing a decoy with the relevant surface proteins, but they're
unlikely to work with HIV because it's so _simple._ When an antibody finds its
antigen, it signals the immune system to consume the pathogen and learn about
it if it hasn't seen the invader before. Since antibodies share a chemical
structure (like DNA and RNA, except more complex), cells in the immune system
can memorize the antibody and produce it even if it isn't present in our
genetic code. This process is one of the most amazing adaptations in the
animal kingdom, allowing complex organisms to compete with the microscopic in
the evolutionary arms race, but the immune system needs to see the antibody
and pathogen in order create mature B-cells, which adapt to bind to the same
pathogen as the antibody. HIV is small, simple, and doesn't have many unique
features on the viral package (which contains the RNA) so it'll likely be very
hard to produce a decoy for the antibody to latch on to.

------
mrcactu5
there's a lot of genetic variation in HIV due to natural selection. in the
process of replicating they make many different strains -- mostly very similar
to one another.

here is an HIV sequence database
[https://www.hiv.lanl.gov/content/index](https://www.hiv.lanl.gov/content/index)
[https://hivdb.stanford.edu/page/who-resistance-
list/](https://hivdb.stanford.edu/page/who-resistance-list/)

if you take medicine, get off them and try to get back on your medicine, you
may find your medicine no longer works.

that being said I don't quite know what "neutralize" means in this context,
but the NIH seems to feel this result has wide applicability.

------
wolf550e
Can HIV be eradicated completely by all current patients dying (within, say, a
century) without transmitting it to anyone else?

~~~
ionforce
Surely there has to be a better way to phrase this.

~~~
eganist
"Could HIV be eradicated by merely halting all transmission?"

Yes.

~~~
atmosx
Yes, but that would require an effort by an organisation like WHO of a scale
never seen before. I would be very _proud_ of the human species if we could
pull this off.

I think, as a species, we'll master time-travel before consensus...

~~~
andrepd
Smallpox was a plague of similar proportions, and the world community got
together and pulled the massive feat of erradication in a decade.

~~~
atmosx
It's not like HIV.

------
c3534l
I've been hearing about "this looks like a cure for AIDS!" at least once a
year since the 90s. It always just needs to go through FDA testing and
approval and then evaporates. What we've gotten instead is incremental
improvements in the treatment of the disease. Maybe if you tell me there is a
new treatment that completely cures some 1% of those treated I'll buy it. But
this, this is preliminary research.

------
iaw
I feel like the frequency of the "scientific breakthrough" headlines that led
to nothing has muted my enthusiasm for remarkable findings like this.

There is a huge difference between the NIH announcing a finding and the
sensationalist science journalism that is typically inaccurate. I wonder if
this divergence erodes the public trust in science.

~~~
nneonneo
An earlier antibody in the same family, VRC01, is in Stage IIb clinical trials
for the treatment of HIV. Medical science is slow and extremely methodical,
but it can produce practical results. You just have to have patience.

~~~
ufo
I think the problem is that in popular news you often just get the impression
that a "breakthrough" happened but it isn't super clear what the scientist
actually did, what are the limitations of their work and what you should
expect from future research.

So instead of seeing news that say specific things like "this might lead to a
monoclonal antiboody treatment in 10 years" or "this could help vaccine
research" you end up with a bunch of headlines that sound as if AIDS is going
to be cured tomorrow.

~~~
iaw
Thanks ufo, that's the point I was trying to make.

------
peter303
Since the discovery of the virus 32 years ago there have been a large number
of treatments successful in animals or the test tube, only to fail in humans

------
hackuser
If you feel these discoveries are important and you are an American, let your
Congresspeople know that you support NIH funding.

------
throw16
the patient has to take it the rest of their life ...the perfect money maker

