Plant derived monoclonal antibodies vs HIV-1

Ive written about modifying plants to do lots of fun things (vaccines, counter allergies, etc) in the past:

Green our vaccines!

Green our vaccines! Part II

Green our vaccines! Part III

Green our vaccines! Part IV

Unfortunately, this kind of technology has been held back by luddite/anti-biotechnology pressure from the general public. It has *not* moved forward as much as it could have:

About 15 years ago, it was thought that genetically engineered crops would be widely used to produce human proteins for use as drugs. When Dr. Whaley and Dr. Zeitlin (the scientists behind the anti-Ebola therapy currently in the news-- erv) were both researchers at Johns Hopkins University in 1998, they published a paper with Monsanto scientists about a soybean genetically engineered to produce an antibody against genital herpes. But that idea has largely been abandoned, especially when it comes to using food crops, because of concerns that drugs produced in crops might inadvertently get into someone’s cornflakes.

(H/T AgBioWorld)

But readers really caught on to the experimental therapy for Ebola. Growing antibodies for deadly diseases in plants is freaking cool. This is a fantastic opportunity to pull the general public away from random dingbats on the internet, and towards incredibly cool science.

A frequent question I heard after people learned about how the 'top secret' treatment was made, was 'Are we making antibodies in plants for any other diseases?'


Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems

Here is the idea: In HIV World, scientists have isolated a handful of broadly neutralizing antibodies. These antibodies have the ability to neutralize >90% of HIV-1 variants.

That is neat... but unfortunately these antibodies are of limited utility. We have had them for decades, and they have not translated into a useful therapy, nor have they informed design of an efficacious HIV vaccine.

These antibodies are interesting laboratory reagents... and thats it.

Other scientists, however, are trying to figure out how to put these reagents to good use. David Baltimores lab is trying to turn them into gene therapy products. And several other labs would like to put these antibodies into gels, in combination with anti-retroviral drugs, to prevent HIV infection. Or, giving these antibodies as a therapy to HIV+ moms right before they give birth, to prevent transmission to baby.

For anti-HIV gels and immunotherapy, you would need to produce lots of anti-HIV antibodies (you know where this story is heading) so they want to produce these proteins in plants!

Before you get too excited or accuse the US government of hiding a cure for HIV/AIDS, what this particular paper really illustrates is how far away we are from this being a 'standard' protocol-- They are testing very, very basic (but very, very necessary!) concepts:

1-- Can we make anti-HIV antibodies in plants?

They tried several different antibodies. This was a smart move, as maybe one antibody or another just would not like the system, and wouldnt work. No way to know this information on the front end.

2-- How can we alter the sugars on the surface of the proteins?
Proteins made in plants will have fructose and xylose on their surface. Not only can this alter the structure of the protein (sugars effect how a protein folds), those sugars are not supposed to be floating around the human bloodstream. If you are exposed to these plant proteins a lot over the course of treatment, your immune system is going to get pissed off.
With the Ebola antibodies, they got around the plant-sugar issue by using a genetically modified plant. In this paper, they added a message to the anti-HIV antibody protein to get it 'stuck' in the endoplasmic reticulum. Proteins need to travel from the ER to the Golgi to have their sugars modified/add complex sugars like fructose and xylose. If its stuck in the ER, it only gets mannose (which is 'safe' for human proteins).
The good news is, they could make antibodies free of fructose/xylose this way, BUT, they didnt get as much protein.
3-- Do the plant derived anti-HIV antibodies still stop HIV?
There is no point in making an anti-HIV protein fast/cheaply if it isnt still anti-HIV at the end of the synthesis process.
Happily, the antibodies produced in plants neutralized HIV variants just as well as the antibodies grown in mammalian cells. And, the antibodies were capable of mediating ADCC (antibodies stick to an infected cell, and other immune cells come along and kill the infected cell).
This is great news!
Growing anti-HIV antibodies in plants is nowhere near a 'cure for HIV/AIDS'. You cant just inject someone with an antibody and expect a 'miracle'. You have to administer the right antibodies in the right form at the right time, to get to the right location in the body at the right concentration.
We dont know what will happen if we inject HIV+ humans with these antibodies.
We dont know whether these antibodies will stay stable in an anti-HIV gel.
We dont know if they will stop Mother-to-child transmission during birth.
All we know, is we can make these antibodies in plants, sans plant sugars, and they work.
If you guys want plant derived antibodies to combat HIV, or, any other disease, you need to support the scientists doing the work. Not the random internet dingbats.

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Sorry, it's the reccourse of someone who WILL NOT consider anyone else's point of view for ideological reasons to claim the counters and failures of your preferred sitution is due to the mental failings of others.

No luddite is causing this problem.

What holds back this cure is that the companies make vastly better ROI on making "Super Cold and Flu Remedy Ultra Max", with the "super plus double good version" ready in the wings for when the patent on SCFRUM is to expire.

Moreover, the GMOs wanting to be produced first are NOT HIV or other "worthy" goals but the mass production of profitable cropping GMOs to ensure a secure and profitable revenue stream.

When I worked in an HIV vaccine lab my boss was super dismissive of the whole monoclonal-antibody treatment thing, saying that it had been tried in the 1980's, and it hadn't worked then because HIV mutates too fast, so why were people trying again? (He was also a bit grumpy about our lack of progress on our vaccine testing system.)

But it's a good question: Can we build a monoclonal antibody production system that would be flexible enough so that as HIV mutates and the antibodies don't bind any more, the plants could be adapted to make antibodies for new targets?

By JustaTech (not verified) on 12 Aug 2014 #permalink

Given the ethical issues surrounding the production of monclonial antibodies in mice, it's good to see plants being utilized in this regard.