Archive for November, 2013

Saudi Arabia must be transparent to fight MERS virus

21 November, 2013

See on Scoop.itVirology News

MERS virus provides another reason for Saudi Arabia to be transparent.

SLOWLY OVER the past year, a novel respiratory virus has claimed victims in the Middle East, primarily in Saudi Arabia. It comes from a species known as coronavirus, which, through an electronic microscope, looks like a spiky blob. The virus has been named Middle East respiratory syndrome, or MERS. According to the World Health Organization (WHO), of the 157 laboratory-confirmed cases since September 2012, 66 people have died.

It is not uncommon for humans and animals to exchange dangerous pathogens. In the past decade, Severe Acute Respiratory Syndrome, or SARS, also a coronavirus, rose out of China, perhaps from bats; the swine flu pandemic originated in Mexico; and avian flu has remained an ever-present threat to humans. What’s most important about these diseases is whether they are transmissible from human to human. It turned out that SARS and swine flu spread quickly among people.

Transfer from animals is also suspected in MERS; reports have pointed to bats and camels as possible sources. But there is a big puzzle: Many of the people who came down with MERS were not exposed to bats or camels. So far, close contact between humans seems to provide some means of transmission, although it is still not clear how readily. The fear is that if the virus did become easily transmissible, it could spread fast and be fatal to many.

A study published this month in the Lancet Infectious Diseases carried some unsettling findings about MERS. The study, by an international team, suggested that many cases are being missed, perhaps because they are not severe. The researchers estimated that 62 percent of the cases with human symptoms may not have been diagnosed as MERS.

Ed Rybicki‘s insight:

Frightening stuff…the fact that a MERS epidemic may be growing slowly under our noses, because of the security concerns and traditional lack of access by outsiders to Saudi information, is highly concerning for the rest of us.

Do people learn NOTHING from history?  The only reason SARS got to be a problem was because Chinese authorities sat on information – and the only reason we later got on top of SARS was by sharing information.

Yet here we are, a decade or so later, and the same thing is happening with MERS.

See on www.washingtonpost.com

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“Circovirus kills dogs [in USA] in days, no vaccine”: disinformation spreads….

18 November, 2013

See on Scoop.itVirology News

Cases of dogs contracting the virus have already been reported in multiple [US] states. Currently there is no vaccine available to treat the virus and severe cases could kill dogs in days.

Ed Rybicki‘s insight:

This is a highly misleading report in a national US daily: basically, it is calimed that "circovirus" is spreading across the USA, killing dogs.  

At one point in the USA Today clip, they claim that "…the virus originates in pigs and birds, and has mutated…".

Really??  The VERY distinct circoviruses that infect pigs – two kinds, both called PCV, only one nasty – and birds (MANY kinds) have spread to dogs??

This is, of course, complete nonsense: the only reports of actual virus sequences – see here (http://jvi.asm.org/content/86/12/7018.full) and here (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647419/) – showed that there was a distinct circovirus (capsid and replicase proteins share <25% and <50% identities, respectively, with those of the known animal circoviruses), and that isolates from different dogs had very similar viruses.  Thus, a hitherto undiscovered circovirus that is distinct from any previously characterised agent, is infecting dogs in the USA.

But is is NOT known to what extent.  That still needs some work!  Meantime, USAToday: get your sceince right!!

See on www.usatoday.com

Immune suppressor makes one flu vaccine work for many viruses [but is explained badly]

5 November, 2013

See on Scoop.itVirology News

The flu kills over 250,000 people every year. Flu viruses change constantly, so they can evade our immune systems, the immune systems of other host species, and the vaccines we throw at them. Each seasonal vaccine can, at best, protect only against the current circulating strain of virus—but not emerging variants. (Just so we’re clear on this, YOU SHOULD STILL GET VACCINATED. Reread the first sentence.) And we currently have no way of knowing which strain might become a pandemic, or when or where such a strain might arise.

Making a universal vaccine, or at least one that could counter more than one subtype of the virus, is a priority. Efforts thus far have failed, because most of the proteins that are conserved between the different influenza subtypes are inside the virus rather than on its surface, which typically makes them tough for antibodies to access. But researchers have recently found a way to render one vaccine protective against a number of different subtypes.

 

Influenza variation graphic from Russell Kightley Media

Ed Rybicki‘s insight:

This is all very well, and a brilliant exemplification of my adage that "Hypotheses are the refuge of the small-minded", aka "Discovery trumps hypotheses every time" – BUT I have a serious problem with the reasoning for why it works that is given in the article.

 

Diana Gitig says:

"Rapamycin suppressed class switching, so mice that got it along with their vaccine had more IgM class antibodies, many of which tended to be less specific to HKx31. Irony number three: these less specific antibodies might not bind as strongly to the HKx31, but it is precisely this reduced affinity that may allow them to bind to the equivalent protein on other flu strains."

Um.  That flies in the face of all the immunology I have imbibed since 1976, and what I have taught since 1984 or so.  That is, that B cell receptor / IgM/D binding affinity starts out low, then increases by hypermutation so that the eventual class-switched antigody has high binding affinity.  Along with this, specificity starts out high – the antibodies bind only a narrow range of related epitopes – and becomes wider, as increased affinity allows binding to a wider range of related sequences / structures.

Thus, the statement that "… it is precisely this reduced affinity that may allow them to bind to the equivalent protein on other flu strains" is nonsense, as far as I am concerned: it is the fact that the antibodies have INCREASED affinity, AND are multivalent IgM, that allow them not only to bind to related sequences, but increase their neutralising ability relative to the equivalent IgG/A that would result from class-switching.

Am I wrong?

See on arstechnica.com

Emergency response vaccines for H5N1 influenza in South Africa

1 November, 2013

Our group has been working for some time now – since 2006, in fact – on investigating the feasibility of providing South (and southern) Africa with emergency response pandemic influenza vaccines.  The research was initiated after the Virology Africa 2005 conference that Anna-Lise Williamson and I organised in the Cape Town Waterfront in November of that year – when a senior WHO official warned us in his talk that “…if a pandemic hits, you are on your own: no-one will give you any vaccine”.

A group of us sat down afterwards, and discussed the feasibility of looking at emergency response vaccine(s), given that we had no capability in the whole of Africa to make flu vaccines.  Anna-Lise and I put together a proposal, with the highly pathogenic avian H5N1 influenza A as a target, which was funded on a once-off one-year basis by the Poliomyelitis Research Foundation (PRF) here in SA for 2006 – and then again by the PRF as a three-year Major Impact Project  (MIP) from 2008-2010, and subsequently to a lower level by both the PRF and the Medical Research Council of SA.  What made it all the more impressive for a South African project was that we had proposed expressing a protein-based vaccine in plants – quite a revolutionary prospect at the time, but something that followed on from the highly successful production of Human papillomavirus virus-like particles by transient expression in Nicotiana benthamiana by  James Maclean, working as a postdoc in our lab at the time.

However, some of the most important work was done early: James was very quick to get the haemagglutinin (HA) gene for the A/Vietnam/1194/2004 strain of H5N1 synthesised by GeneArt in Germany, and cloned into the same Agrobacterium tumefaciens plant expression vectors from Professor Rainer Fischer’s lab in Aachen, Germany, that had been used for HPV.  His initial work showed that large amounts of HA protein could be produced, both as soluble protein which lacked a membrane localisation domain, and as the membrane-bound form.  This work formed the basis for a patent application on the transient expression of H5 HA that has now been granted.

Subsequently, when the PRF MIP started, we employed Dr Elizabeth (Liezl) Mortimer and Ms Sandiswa Mbewana to further the work: with collaborators from the National Institute for Communicable Diseases (NICD) in Johannesburg and State Veterinary Services in Stellenbosch, this investigated transient and transgenic expression of soluble and membrane-bound forms and their immunogenicity, as well as a DNA vaccine consisting of the HA genes cloned into Tomas Hanke’s pTH vector.

The protein expression work was published in 2012, as well as being featured here in ViroBlogy at the time.

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What we had managed to show was that we could get excellent production of the H5 HA in both soluble and bound forms, and that especially the membrane-associated form of the protein was highly immunogenic, and elicited antibodies in experimental animals that were appropriately neutralising, indicating its suitability as a vaccine candidate.

Now this all happened despite our running out of money AND Liezl leaving to have a baby…and then we managed to get another paper out of the work, this time on the DNA vaccine side of things.

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We pitched this at the South African Journal of Science as a vindication of the faith in us by exclusively South African funding agencies – and managed to get the cover of the issue in which it appears, thanks to the truly excellent artwork of Russell Kightley from Canberra, Australia.  Front AND back covers, as it happens…!

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And this all made Sandiswa Mbewana, who is now a PhD student on another project, very happy:

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This all came in excellent time to mark the establishment in the Department of Molecular and Cell Biology at the University of Cape Town, of a new URC Research Unit: namely, the Biopharming Research Unit (BRU).

BRU

Watch this space…B-)

Bats and SARS-CoV: deja vu all over again

1 November, 2013

In 2008, I wrote a blog piece entitled “Who do you bind to, my lovely?”, about a couple of papers on SARS-CoV – the coronavirus that causes severe acute respiratory syndrome.  I closed that piece with the following:

“Adding fuel to the speculative fire is another paper in the same issue: this reports that there is evidence of a recombinant origin for SL-CoVs, and there is probably “…an uncharacterized SLCoV lineage that is phylogenetically closer to S[ARS]CoVs than any of the currently sampled bat SLCoVs.”

So let’s all just wait for the next one, shall we?”

…in connection with the fact that horseshoe bat coronaviruses were VERY similar to SARS-CoV, but bound to different receptors.  And we had to wait five years, but heeeeeere we are… these folk may well have found the missing virus(es) that are directly transmissible from bats to humans:

Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

 Xing-Yi Ge et al.

Nature (2013) doi:10.1038/nature12711

Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far [! – my comment; the last ones were pretty close…] more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

So – I told you so…B-)