Archive for May 1st, 2014

An ACTUAL killer virus that could rise from the grave

1 May, 2014
Section through Variola virus.  Copyright Russell Kightley Media

Section through Variola virus. Copyright Russell Kightley Media

Having poo-pooed the possibility of killer viruses roaring out of the tundra to kill as all – see here – I find myself having to reconsider my words.  Just slightly, mind, but a reconsideration nonetheless.

This is because of an excellent post in Nature News recently, entitled “Infectious diseases: Smallpox watch“, by Sara Reardon.  This has raised quite a stir in the Twittersphere, as people speculate on just how likely this is, but I think the article itself does a very good job of discussing the possibility that smallpox could come back from the grave(s).

I have discussed smallpox a number of times in this blog, with one of the most read posts being this one by my PhD student (and now postdoc) Alta van Zyl.  I recall a while back a discussion around just how likely it was that people working on expanding what was the Rietfontein Infectious Diseases Hospital (now Sizwe Hospital)’s premises in Johannesburg, would find live smallpox in coffins of people who died of it at the old Hospital and were buried nearby.

The verdict then was “No” – Johannesburg is too hot, and the was seen to be NO chance of the virus surviving the rapid putrefaction that occurs in these parts.

Sara Reardon’s essay, however, raises the real, if rather remote, prospect of there being live smallpox in mummified corpses which have either dried out at low temperatures, or been frozen soon after death, in permafrost.  She says that

“A more likely source of infectious virus would be frozen bodies. Influenza viruses seem to be able to survive freezing in lakes and may thereby infect migrating birds…”

Now the good thing is that people have actually gone out looking for live virus in just such potential sources, and found nothing except fragments of DNA.

However, she also says:

“Another concern is that smallpox could escape from a secret cache. Few biosecurity specialists believe that the two stocks kept at the CDC and VECTOR are the only ones in existence. For instance, variola could very well be in the freezer of someone who defected from the Soviet Union…”

Now, the old Soviet Union had an active programme on weaponising smallpox, with some sources claiming than “several tonnes” of material were eventually made.  There is even evidence that smallpox escaped from a facility in Aralsk, Kazakhstan, in 1971.   What is not so clear is where any of this material is NOW, and in what state it is.

Time to work on the emergency-response smallpox vaccines and strategies, folks – even if you use the potential threat of monkeypox as the reason!

 

 

Recombinant Bluetongue virus vaccines – or some, anyway

1 May, 2014
VIRUS-rota-200

General model of reo-like viruses. Copyright Russell Kightley Media

I picked up yesterday – via @MicrobeTweets’ Twitter feed – on a very useful list of papers in a “Virtual Special Issue” of Elsevier’s recent coverage of vaccines – for “World Immunization Week”. Great stuff, I thought to myself, as I browsed the list – and downloaded at least those that were Open Access, or which I can get via our Libraries’ IP range.

“Even better!”, I thought, as I saw a review entitled “Recombinant vaccines against bluetongue virus?”  A meaty, well-sourced review, I thought; good reading for me and my students / coworkers, and good meat for upcoming Introductions for papers yet to be written.  Indeed, it promised the following:

“The multiple outbreaks of BTV in Mediterranean Europe in the last two decades and the incursion of BTV-8 in Northern Europe in 2008 has re-stimulated the interest to develop improved vaccination strategies against BTV. In particular, safer, cross-reactive, more efficacious vaccines with differential diagnostic capability have been pursued by multiple BTV research groups and vaccine manufacturers. A wide variety of recombinant BTV vaccine prototypes have been investigated, ranging from baculovirus-expressed sub-unit vaccines to the use of live viral vectors. This article gives a brief overview of all these modern approaches to develop vaccines against BTV including some recent unpublished data.”

So, I parked the conveniently Open Access-ible window away on the side of my desktop, to be got back to with every expectation of delight.

Until I read it, that is: well-sourced it may be; excellent in its coverage, it is NOT.  In fact, apart from a brief discursion on subunit vaccines – concentrating almost exclusively on baculovirus / insect cell-produced proteins – it is almost exclusively concerned with live viral vectors for bluetongue proteins, and of poxviruses in particular.  Now, this is all very well, if that is what they work on – but to dismiss one of the potentially most exciting developments in recent Bluetongue vaccinology like this:

“VLPs of BTV have been also produced in plants recently using the cowpea mosaic virus and their use in a vaccination study produced no clinical manifestations in sheep after homologous challenge, although viremia was no [sic] evaluated (Thuenemann et al., 2013).”

– boggles the mind somewhat.  Really?  That’s all they have, compared to the screed immediately before it on baculovirus-produced antigens?  They get the expression system wrong – it is an Agrobacterium tumefaciens-mediated transient expression system in Nicotiana benthamiana involving a Cowpea mosaic virus-derived enhanced translation vector – and neglect to mention that the VLPs produced are as good as anything produced in insect cells; will be FAR cheaper to produce, and WORKED AS WELL AS THE CONVENTIONAL ATTENUATED LIVE VIRUS VACCINE IN A CHALLENGE EXPERIMENT IN SHEEP.  True!

This is a big deal, folks, really: successful production of significant amounts of VLPs requiring simultaneous expression of 4 structural proteins of BTV-8 in plants AND their subsequent assembly, AND performing as well as the standard vaccine in an animal trial.  But no – not good enough for our review’s authors….

I must declare vested interests up front here: first, we work on plant-made recombinant Bluetongue vaccines; second, I and others in my group are co-authors of the paper whose lack of coverage I am aggrieved about.

But that’s not the point: what IS the point is that this review is a slipshod piece of work that damns our collective endeavour with faint praise, in community that might otherwise have been alerted to an alternative to the far-too-expensive-for-animal-use baculovirus expression technology.

Ah, well.  I suppose that’s what blogs are for B-)