Archive for the ‘Viruses’ Category

More Surprises in the Development of an HIV Vaccine

14 November, 2014

More Surprises in the Development of an HIV Vaccine

In the current issue of Frontiers in Immunology, Jean-Marie Andrieu and collaborators, report results from non-human primate experiments designed to explore a new vaccine concept aimed at inducing tolerance to the simian immunodeficiency virus (SIV) (1). This approach, which is significantly different from other vaccine concepts tested to date, resulted in a surprisingly high level of protection. If the results are confirmed and extended to the human immunodeficiency virus (HIV), this approach may represent a game changing strategy, which should be welcomed by a field that has been marred by mostly disappointing results.

 

HIV Graphic from Russell Kightley Media

 

Source: journal.frontiersin.org

This is a commentary by two well-respected friends of mine on a very surprising result published by the Andrieu group recently, which seems to have been ignored by the mainstream HIV vaccine world.

This is not surprising, in that Andrieu is an outsider in this field – he is a cancer researcher – but is typical of the disappointing tendency in science to ignore contributions from outside the various "Golden Circles" that exist for various specialties.

Something that should elicit interest, though, is that this group has shown that a previously obscure 

"…population of non-cytolytic MHCIb/E-restricted CD8+ T regulatory cells [that] suppressed the activation of SIV positive CD4+ T-lymphocytes".

This is interesting because Louis Picker’s groups’ recent findings, announced at the recent HIVR4P conference in Cape Town, highlighted the involvement of MHC-E proteins in what amounted to a cure of SIV infection in macaques by a modified Rhesus cytomegalovirus (RhCMV) HIV vaccine vector (see here: http://www.iavireport.org/Blog/archive/2013/09/13/cmv-based-vaccine-can-clear-siv-infection-in-macaques.aspx). 

I tweeted at the time:

"Universal MHC-E-restricted CD8+ T cells – break all the rules for epitope recognition"

Could this be a link between the two mechanisms – both from way outside the orthodoxy, I will point out?

It will be interesting to see.

See on Scoop.itVirology News

Genetic Data Clarify Insect Evolution

13 November, 2014

Researchers create a phylogenetic tree of insects by comparing the sequences of 1,478 protein-coding genes among species.

Using an unprecedented quantity of genetic sequence information from insects, researchers have assembled a new phylogenetic tree showing when these invertebrates evolved and how they are related to each other. The tree suggests that insects evolved approximately 479 million years ago, around the time when plants colonized land, and that insects are most closely related to cave-dwelling crustaceans. The new study, published today (November 6) in Science, also confirms some previously suspected family groupings.

 

Source:

This bolsters my contention that it was the coevolution of insects and plants – because what else were insects going to eat? – that has driven much of viral evolution as well.

Because what else was there to infect? Basically, the only terrestrial organisms around some 450 million years ago were primitive green plants, insects, fungi and bacteria. So insects ate plants, fungi infected plants, viruses in insects entered plants and vice-versa; fungi got involved as well, and possibly even bacteria.

I have speculated on the possibilities here (http://www.mcb.uct.ac.za/tutorial/virorig.html), but it is pleasing to see new science that reinforces some of what I have been spreading about for some years now B-)

See on Scoop.itVirology and Bioinformatics from Virology.ca

Virology Africa 2015: consider yourselves notified!

7 November, 2014

Dear ViroBlogy and Virology News followers:

Anna-Lise Williamson and I plan to have another in our irregular series of “Virology Africa” conferences in November-December 2015, in Cape Town.

As previously, the conference will run over 3 days or so, possibly with associated workshops, and while the venue is not decided, we would like to base it at least partially in the Victoria & Alfred Waterfront.

We also intend to cover the whole spectrum of virology, from human through animal to plant; clinical aspects and biotechnology.

We intend to make it as cheap as possible so that students can come. We will also not be inviting a slate of international speakers, as we have found that we always get quite an impressive slate without having to fund them fully.

It is also the intention to have a Plant Molecular Farming workshop – concentrating on plant-made vaccines – concurrently with the conference, in order to leverage existing bilateral travel grants with international partners. If anyone else has such grants that could be similarly leveraged, it would be greatly appreciated.

See you in Cape Town in 2015!

Ed + Anna-Lise

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.

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

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

Ebola: “We Could Have Stopped This”

8 September, 2014

Public health officials knew Ebola was coming. They know how to defeat it. But they’re blowing it anyway.

ld, you still just don’t get it. The Ebola epidemic that is raging across West Africa, killing more than half its victims, will not be conquered with principles of global solidarity and earnest appeals. It will not be stopped with dribbling funds, dozens of volunteer health workers, and barriers across national borders. And the current laboratory-confirmed tolls (3,944 cases, with 2,097 deaths) will soon rise exponentially.

To understand the scale of response the world must mount in order to stop Ebola’s march across Africa (and perhaps other continents), the world community needs to immediately consider the humanitarian efforts following the 2004 tsunami and its devastation of Aceh, Indonesia. The U.S. and Singaporean militaries launched their largest rescue missions in history: The United States alone put 12,600 military personnel to a rescue and recovery mission, including the deployment of nearly the entire Pacific fleet, 48 helicopters, and every Navy hospital ship in the region. The World Bank estimated that some $5 billion in direct aid was poured into the countries hard hit by the tsunami, and millions more were raised from private donors all over the world. And when the dust settled and reconstruction commenced, the affected countries still cried out for more.

Source: www.foreignpolicy.com

A seriously hard-hitting article by a very good journalist with a particular interest in infectious diseases.

And she’s right: Ebola was stopped, not once, but a number of times, as long as 38 years ago, in settings that are as or even more desperate in terms of poverty and lack of medics and medical resources.

The problem is, intervention did not occur soon enough this time, or on a scale sufficient to stem the increase in infections that inevitably followed introduction of the disease into urban settings.

It is a matter of amazement to me, that with the ever-present threat of pandemic influenza AND the recent emergence of MERS, that the WHO should have its "…miniscule epidemic-response department slashed to smithereens by three years of budget cuts".

Seriously: faced with diseases that can jump out of camels, or bats, or rats literally anywhere, WHO has to have budget cuts??

See on Scoop.itVirology News

Mucosal SIV Vaccines with Bacterial Adjuvants Prevent SIV Infection in Macaques

2 September, 2014

A new paradigm of mucosal vaccination against HIV infection has been investigated in the macaque model. A vaccine consisting of inactivated SIVmac239 particles together with a living bacterial adjuvant (either the Calmette & Guerin bacillus, lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastic route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8+T regulatory cells that suppressed the activation of SIV positive CD4+ T-lymphocytes. SIV reverse transcription was thereby blocked in inactivated CD4+ T-cells; the initial burst of virus replication was prevented and the vaccinated macaques were protected from a challenge infection. Three to 14 months after intragastric immunization, 24 macaques were challenged intrarectally with a high dose of SIVmac239 or with the heterologous strain SIV B670 (both strains grown on macaques PBMC). Twenty-three of these animals were found to be protected for up to 48 months while all 24 control macaques became infected. This protective effect against SIV challenge together with the concomitant identification of a robust ex-vivo correlate of protection suggests a new approach for developing an HIV vaccine in humans. The induction of this new class of CD8+ T regulatory cells could also possibly be used therapeutically for suppressing HIV replication in infected patients and this novel tolerogenic vaccine paradigm may have potential applications for treating a wide range of immune disorders and is likely to may have profound implications across immunology generally.

 

Graphic of cells involved in HIV immunity from Russell Kightley Media

Source: journal.frontiersin.org

I have heard Jean-Marie Andrieu present this work – and I can understand why there is some skepticism surrounding it, because it is almost too good to be true.

Seriously: SUPPRESSING SIV-specific CD4 T-cell activation results in immunity to challenge infection??

However, and however – if this work is found to have been done well (and there is no evidence it was not), then this really could be a simple, reliable way of immunising people against HIV

Of course, monkeys aren’t people, and SIV is not HIV, so there MAY be a problem somewhere along the line in translating these results into humans – but what if there is not?

Then we may have a vaccine, and kudos to Jean-Marie Andrieu and co-workers to persevering along a difficult road to get their idea tested.

See on Scoop.itVirology News

20 years on, and here we are with Ebola, again

25 August, 2014

Browsing through my own web pages in an effort to clean up dead-end links, and cull tired material, I discovered that my link to an essay I wrote 19 years ago was still live – and as it referred to something written in and put up on our nascent Web server in 1994, means it has a 20-year anniversary round about now.

My essay is

The Student, the Web and the Ebola Connection

or:

Dr Jacobson, are you going to Kikwit?”

…and it is a record of events that resulted in 1994 from (a) an Honours student essay being written on “Emerging Viruses”, and (b) me playing around with the then-very-new WWW server that UCT has enabled – but didn’t tell anyone about, because they didn’t want anyone to use it until they had sorted out policies.  Oh, and (c) – the Kikwit Ebola outbreak in 1995.

I wrote in 1995:

“The whole phenomenon has been an object exercise in the power of the Web as a tool for the wide dissemination of information: we reached not only professional virologists, but also health-care professionals, and – most importantly – the lay public on a large scale”

And of course, this is even more true now – which is why, following the benign guidance of The Guru Cann, I maintain ViroBlogy and Virology News, and heartily recommend a Web presence to anyone who feels they need to disseminate information on topics of specialist and generalist interest to the world at large.

Of course, nearly all the links out of that essay are now dead – including to the original essay, that for a while there in 1995 was the ONLY detailed information on Ebola available on the Web.  So here is Alison Jacobson’s original essay, in full, revealed by going to my teaching material and checking out essays from 1997 and thereabouts:

EMERGING AND RE-EMERGING VIRUSES: AN ESSAY

Of course, I also maintained a daily update on the Kikwit outbreak, and then a couple of the next ones, before the Web caught up with me and it became easier to just trawl it for news via Google and its predecessors.  It still makes interesting reading, though, to go through some of what was posted from the disease frontlines back in the 1990s – and to remember that I had the TIME to do that kind of thing!

Where we are now

Well, here we are with what is the worst outbreak of Ebola in history, and here am I – again – trying to keep up with it.  This time, by the very excellent medium of the Web news aggregator Scoop.it, where I have established Virology News as a means of quickly and easily getting news out to the public.  Again, following the very excellent example of TGC, but also Chris Upton, who babied me along by letting me co-curate his Virology and Bioinformatics site.

Of course, there is a new angle to this outbreak – and that has been the compassionate use of a plant-made monoclonal antibody cocktail (ZMapp), hitherto only tested preclinically in a primate model.  Fortuitously, this all happened while I was finishing off a review on plant-made viral vaccines, so I reported on it – with references – here on ViroBlogy.

I was also able to report on it in my Plant Molecular Farming news site, with some authoritative statements from pioneers of the technology: Charles Arntzen from the Arizona Biodesign Institute sent through a link for an interview he did, and CNN covered it quite well too.  Charlie also sent through a set of links in an email that he was happy to share:

“The original story

There is a lot of interest from the press in “why tobacco” and “how does it work”?

The other focus is on the politics of scale up of the drug — it seems that criticism of the US is mounting in some sectors of Africa, and elsewhere.   I talked to a Spanish Language radio news station this morning, and the main questions related to “why is this a Secret Drug; are you trying to hide the secret from the world?”    “Is Reynolds tobacco trying to stop the supply of this drug to Africans?”    One guy asked if it was true that the Ebola Virus had been created in a test tube.

It seems that the press is largely to blame for using terms like Secret Drug.   It appears that they are also trying to mount political pressure to make a lot more of the drug to help Africans.   [This was] a nice job answering some of this….”

And at time of writing, the outbreak was still raging, had spread to Nigeria, and airlines were banning travel to half of West Africa – and alarmist tourist firms were advising people not to come to South and East Africa, as well.  The WHO has also said the impact is probably much greater than reported.

And Alison Jacobson is alive and well, and NOT working in virology any more.  Sadly!

5 Viruses That Are More Frightening Than Ebola

20 August, 2014

By Elizabeth Palermo, Staff Writer
Published: 08/15/2014 01:58 PM EDT on LiveScience
The Ebola virus has now killed more than 1,000 people in West Africa. Although the mortality rate of the most recent outbreak isn’t as high as in previous events, it’s still the case that most people who become infected with Ebola will not survive. (The mortality rate is about 60 percent for the current outbreak, compared with 90 percent in the past, according to the National Institutes of Health.)

1. Rabies

2. HIV

3. Influenza

4. Mosquito-borne viruses

5. Rotavirus

 

 

Source: www.huffingtonpost.com

Amen!  I have a fondness for Ebola simply because it is so spectacularly nasty, but it has killed fewer people in 40 years than flu or rotavirus does in 1.

Seriously: just like charismatic animals like elephants and tigers get all of the headlines when it comes to being endangered, rather than the humble tree frog(s), so do Ebola and Marburg get all of the attention when it comes to reportage on virus epidemics / pandemics.

See on Scoop.itVirology and Bioinformatics from Virology.ca


Follow

Get every new post delivered to your Inbox.

Join 622 other followers