Archive for May, 2014

HPV type 16 E7 protein bodies cause tumour regression in mice

26 May, 2014

See on Scoop.itIIDMM News

Background

Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer.

Methods

In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV – type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera(R), a self-assembly domain of the maize gamma-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems.

Results

High-level expression of the HPV 16E7SH protein fused to Zera(R) in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression.

Conclusions

The fusion of 16E7SH to the Zera(R) peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera(R) PBs.

 

I thank Russell Kightley Media for use of the HPV/cervical cancer graphic

Ed Rybicki‘s insight:

I keep saying – you gotta go green…B-) And here we are, suiting action to words.  

Modestly, of course.  

Well done to Mark Whitehead and Thomas Oelschlager; thanks to Inga for sticking with a difficult ms – and thanks Era Biotech for the technology!

See on www.biomedcentral.com

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Virus experiments risk unleashing global pandemic, study warns

21 May, 2014

See on Scoop.itVirology News

Benefits of scientific testing in the area are outweighed by risks of pathogenic strains spreading round world, say researchers

Ed Rybicki‘s insight:

…and others say "Rubbish!"  I particularly like this bit:

 

"[Ron] Fouchier said…the authors had misinterpreted published data to arrive at their risk of someone picking up a virus in the laboratory. "The truth is that scientific research has never triggered a virus pandemic.""

The report goes on to say:

"Lipsitch and Galvani point out that a flu strain that spread around the world from 1977 to 2009 was probably released in a laboratory accident."

Yes.  But.  That was from the old Soviet Union – and they had a number of nasty things escape from laboratories, including anthrax and weaponised smallpox, by all accounts.

 

See on www.theguardian.com

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-)