Archive for October, 2014

ZMapp in an HIV context

30 October, 2014

It was truly a pleasure to run into Kevin Whaley of Mapp BioPharmaceutical today, here at the HIVR4P inernational conferrence in Cape Town – so I made him come and have coffee with me and Anna-Lise, so we could chat about molecular farming.
Of course, it is the ZMapp plant-made therapeutic antibody that has set the molecular farming world alight, that was the main topic. Apparently Mapp is looking at a January 2015 date for a clinical trial in the affected West African countries, alongside the adenovirus and RSV-vectored vaccines. The plants for the production of the thousands of doses that will be needed – and recall, that’s a couple of grams per dose at 50 mg/kg – are already growing at Kentucky Bioprocessing in Louisville, so one imagines that a pile of work will be coming their way in the near future.
It’s also sobering to realise that even though plants ARE a more scalable and POTENTIALLY cheaper means of production of biologics, that therapeutic antibody production in particular, MAY be better suited right now to conventional technologies, such as CHO cell or even fungal production.
This is because large quantities of MAbs will be needed, and there is established capacity for production of hundreds of thousands of litres of cell culture right now, and yields and production costs have been driven right down to US$10 / gram for MAbs already, according to Kevin.
This partly answers a question I had during the HIVR4P sessions: if one is to use 20-50 mg/kg dosages for anti-HIV neutralising MAbs such as VRC01, how would it be remotely possible to make the amounts required for use in a developing country setting, where the patient can almost definitely NOT pay?
I still think there is a role for plants – but maybe this will be in the area of prophylactic use of MAbs, where much lower doses may be effective because there is not nearly as much virus to neutralise or inactivate.
And of course, Mapp is involved here too, with plant-made VRC01 in particular being incorporated into microbicides.
A great bunch of people, with really noble aims.

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Rabies Vaccine Protects Nonhuman Primates against Deadly Ebola Virus

26 October, 2014

The research team is pursuing the inactivated rabies/Ebola vaccine for use in humans. The live vaccine is being developed for use in protecting wildlife at risk of Ebola virus infection in Africa, which could also serve to prevent transmission into the human population.

Source: www.niaid.nih.gov

I missed this one at the time – and it is an interesting piece of news.  Basically, the research team cloned the Ebola envelope glycoprotein GP1 into the extant rabies virus vaccine strain genome, and tested a live version, a replication-deficient version, and a killed whole virion version in macaques.

Their results are interesting enough – 100% protection against challenge for live, 50% for the other two – that they plan to follow up to see whether or not additional doses could improve protection in the two non-replicating versions, and to make a “multivalent filovirus vaccine”.

This can only be welcome news against the backdrop of the still-ongoing epidemic in West Africa – where two other vaccines (recombinant vesicular stomatitis and chimpanzee adenovirus) are probably going to be trialled next year. The rabies version at least is based on a very well characterised vaccine that already protects against an extremely deadly disease – it remains to be seen how well the other two do.

I forgot to mention that I found reference to this article on “The Zombie Research Society”‘s blog site: http://zombieresearchsociety.com/archives/25562. A very apt place if one considers the parallels that are already being drawn between Ebola and a “zombie virus”.

And because I like zombies B-)

See on Scoop.itVirology News

Resurrecting Smallpox? Easier Than You Think

17 October, 2014

The virus’s genome is already online. You just need the right lab.

Source: www.nytimes.com

Weeeeeellll…yes and no. Smallpox is a BIIIIG genome – not far off in size to the bacterial genome famously resynthesised by Craig Venter et al., a while ago.  This means it would be a huge undertaking, cost a LOT of money, and need sophisticated facilities to do it.

Not something your average cave-dwelling fanatic could do, then!

States could do it, however: a well-funded lab in even a country like North Korea could theoretically resynthesise a poxvirus – but why bother??  We have vaccines against smallpox right now; growing poxviruses and vaccinia virus in particular is a well-established biotechnology still.

SO I think this is an artificial concern, to be honest. 

See on Scoop.itVirology News

Packs of wild dogs spread Ebola after eating corpses!! Or…not, maybe?

13 October, 2014

Packs of wild dogs spread Ebola after eating corpses

The ever-evolving Ebola narrative is broaching into ludicrous territory, with reports now claiming that wild dogs are going around digging up the rotting remains of deceased victims and eating their flesh in the streets. Special Ebola graveyards, where the dead are being buried in haste and at shallow depths, are reportedly feasting grounds for these dogs, which officials say are capable of spreading the disease to humans.

The Daily Mail says Liberian villagers first came across the dogs while going about their daily routines. Right in the middle of busy streets, they said, hungry hounds were allegedly seen ripping through rotting corpses, to the shock of onlookers. After determining the source of the bodies, it was revealed that shallow graves were to blame.

Source: www.naturalnews.com

Stephen Korsman of the Division of Medical Virology at UCT just alerted me to this article, in some distress because they had misquoted him and used his comments out of context.  This is a rather wild, sensationalist and highly inaccurate piece from a fringe web site that seems to have blocked me from commenting, because of previous criticism.  So, I’ll just do it here.

They comment: "Logically speaking, it makes little sense that asymptomatic dogs are possible Ebola carriers while asymptomatic humans are not. There exists no credible science to substantiate this apparent inconsistency beyond the baseless claims made by government health officials."

Utter garbage: bats carry Nipah virus, SARS-CoV, Ebola, Marburg AND rabies essentially asymptomatically – and can transmit ALL of them to other mammals. So too can deer mice transmit Sin Nombre hantavirus in the south-western USA without showing symptoms.  Rodents transmit Lassa fever virus in West Africa every year, again without being symptomatic.  Mice can transmit various South American haemorrhagic fever viruses without obviously being sick. I wish they would get their facts straight: this is is very easily checked!

See on Scoop.itVirology News

Norway to get world’s last dose of ZMapp – update

8 October, 2014

The Norwegian woman, infected by the Ebola in Sierra Leone and currently receiving treatment in Oslo, will get the last dose of the virus treatment medicine ZMapp

Source: m.thelocal.no

…and yet again, the emphasis is on how slow it is to make it – when the whole point of biofarming and transient expression is that it is supposed to be QUICK to make things, and easy to scale up production!!

What is the problem here?  KBP has facilities – or says it does – for large-scale production of proteins via transient expression in N benthamiana via rTMV or even BeYDV-based vectors. SO why has it been so difficult to make more ZMapp??

Why, in fact, are we told via other reports that the US government is considering getting Caliber to make it, or even to make the cocktail in CHO cells, because of capacity, when KBP has the equipment?

It can’t be supply of plants, surely: if they’d planted out a big greenhouse or two of N benth the moment ZMapp hit the news, they’d have enough to make many grams of ZMapp right now – given that it takes just a few days of incubation post-infiltraiton to make the protein.

Surely it’s not a protein purification thing – because THAT’S pretty quick too, once the plants have been mushed.

So what IS the bottleneck? cGMP requirement? Lack of certified protocols / equipment? Can someone tell us??  Otherwise, a posterchild for biofarming will end up being made by good old stainless steel cell culture technology, and our favourite way of doing things will have been found to be wanting.

NOTE ADDED 10th October:

Never let it be said I was unwilling to get schooled by a former colleague…Kenneth Palmer just told me what the problem is:

“You may not be aware that the human dose of Zmapp is 12 grams per patient, 3 infusions of 4 grams each.  Check the dose in recent Nature paper. If yield of one antibody is 100 mg per kg and you have to produce three antibodies for Zmapp… If you do the arithmetic you will see why the process is “slow””.

So…. Doing just that, you end up with 30 kg N benthamiana per gm of ZMapp as a best-case yield – meaning 360 kg PER PATIENT.

That’s a LOT of N benth – and tooling up for that sort of plant production takes time. Thanks, Kenneth!

I would be VERY interested in a cost breakdown of ZMapp vs CHO cell-produced MAbs – because producing at that sort of scale MUST be prohibitively expensive in stainless steel?

 

See on Scoop.itPlant Molecular Farming