Proof of principle for epitope-focused vaccine design – or is it?

6 February, 2014

See on Scoop.itVirology News

Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

Ed Rybicki‘s insight:

Yes.  Um.  Well.  I have just heard a lecture by the redoubtable Marc van Regenmortel (disclosure: my former mentor) pointing out how this strategy is highly UNLIKELY to be "the" way of generating antigens that are likely to be good immunogens – and I was convinced.

Now this.

Um, he said.  And…the MHvR arguments still stand, I think: why should something that supposedly looks like the thing that supposedly elicited a strongly neutralising antibody, elicit a strongly neutralising antibody?

OK, it apparently did here – but as a general rule?  Do we KNOW what "good" neutralising epitopes look like in 3D?  Because linear epitopes are really just an approximation to what real epitopes are, and epitopes are in fact just those things that BIND antibodies – NOT necessarily what ELICITS them.

Damn, I’m sounding like Marc – must be catching!

But seriously: antibodies are the membrane receptors of B cells; they are generated by random recombinations, and then selected by adventitiously binding another molecule that is not self; they are then further selected by repeated rounds of binding, while undergoing random mutations affecting their hypervariable regions, while weak binders are selected AGAINST by Tregs.

And end up both with higher affinity, and more broad binding to related "epitopes" as a result.

Incredibly hard to duplicate as general phenomenon, I would surmise.

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Have we reached the beginning of the end of the fight against HIV/AIDS?

5 February, 2014

See on Scoop.itVirology News

The world is at a tipping point in the fight against HIV/Aids with the number of people getting treatment set to be greater than those being newly diagnosed. But have we really reached the beginning of the end?

Considering the first World Aids Day took place 25 years ago in 1988, it’s a remarkable achievement. Today, there are about 35million people with HIV and Aids in the world, with 9.7million receiving treatment that can enable a long and healthy life.

Ten years ago, just 300,000 people received such treatment so it’s clear there have been major gains, and although experts, campaigners and health practitioners are buoyed the ‘tipping point’ is on the horizon, hard work lies ahead. Erin Hohlfelder, global health policy director of the One Foundation and author of its report The Beginning Of The End?’, feels reaching the tipping point will be a landmark in the fight against HIV and Aids. ‘The disease has been outpacing us for decades, with more new infections than people being added to treatment.

‘To use an analogy, if you had five cuts on your hand, we’ve only had one plaster to treat the cuts, so you’re still bleeding,’ she said.

‘The tipping point, where we have more people living healthy lives through treatment for HIV, than newly infected people, means we’ve caught up with the disease and begun to get ahead of it, so it’s a critical moment. It’s a marker that signals for the first time HIV and Aids is on a downward curve,’ said Ms Hohlfelder.

Ed Rybicki‘s insight:

Great infographic – and potentially good news.  But as I have told my students repeatedly since the mid-1980s, this is a long. slow pandemic – and we are only just over halfway through it.

There’s still a long way to go.

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Cases of New Deadly Bird Flu Surge in China, Experts Say

5 February, 2014

See on Scoop.itVirology News

About 300 cases of H7N9 avian influenza have been confirmed in China, with more appearing every day.

Cases of the new H7N9 avian influenza in China are surging alarmingly, flu experts warned this week.

There are now about 300 confirmed cases, with more appearing every day. Roughly a quarter of the victims have died.

The first human cases were reported only last March. By contrast, the H5N1 influenza virus, another lethal strain that jumped from birds to people, first appeared in 2003 and took almost five years to reach the 300-case mark.

Ed Rybicki‘s insight:

So THIS is the next one?  Possibly?  Good job they’re <a href="">already making vaccines</a>, then, isn’t it?


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Legends of Virology

31 January, 2014

I have been fortunate enough this week to be in Pretoria, at the first Animal and Human Vaccine Development in South Africa Conference (Twitter #AHVDSA): partly because it is a very timeous and necessary meeting to help to establish strategies for this purpose, and partly because there is a significant presence of some legendary figures of international and South African virology.

Marc van Regenmortel – who we count as local even if he lives in Strasbourg – helped Bob Millar and others at the University of Pretoria to organise this meeting. He also used the opportunity of having a bunch of old virological friends visiting him at the University of Stellenbosch’s STIAS to bolster the conference presentations.

So it was that we have Errling Norrby of Sweden with us; we have Fred Murphy of Ebola fame; Marian Horzinek of veterinary virology repute; Marc himself, our iconoclastic viral immunologist; Jose Esparza of the BMG and an eminent poxvirologist – and Jean-Marie Andrieu, an oncologist with an interest in tolerogenic HIV vaccines.

Local legends are present too: we have Daan Verwoerd, legendary orbivirologist and former Director of the venerable and distinguished Onderstepoort Veterinary Institute; Henk Huismans, who did the first molecular work on orbiviruses in the 1970s, and is still active; Bob Swanepoel, doyen of the African haemorrhagic fever viruses.

Good people.

Oh, and of course, me and Anna-Lise Williamson; Dion du Plessis of OVI; Lynn Morris of the NICD; Albie van Dijk of UNW; Glenda Gray of the MRC, among 150 delegates

A great meeting, all in all, and very timely, given the contents of the SA Governmental Bioeconomy Strategy document released recently.


Legends alive: from left, Fred Murphy; Daan Verwoerd; Bob Millar; Henk Huismans; Errling Norrby; Marc van Regenmortel

Jean-Marie Andrieu; Marc van Regenmortel – at a VERY good unofficial dinner


Legends and friends at supper: Marc, Fred, Eric Etter (CIRAD); Jose Esparza; Marian Horzinek; Errling, Anna-Lise Williamson

Biodiversity: So much more than legs and leaves

28 January, 2014

See on Scoop.itAquatic Viruses

Microorganisms inhabit virtually every possible niche on Earth, including those at the outer envelope of survival. However, the focus of most conservation authorities and ecologists is the ‘legs and leaves’ side of biology -the ‘macrobiology’ that can be seen with the naked eye. There is little apparent concern for the preservation of microbial diversity, or of unique microbial habitats. Here we show examples of the astounding microbial diversity supported by South Africa’s ecosystems and argue that because microbes constitute the vast majority of our planet’s species they should be considered seriously in the future protection of our genetic resources.


Ed Rybicki‘s insight:

This is our stab at getting South African science funders to take microbial diversity seriously.  I helped write it, obviously.  And it’s Open Access!

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RNA’s Secret Life Outside the Cell – Wired Science

21 January, 2014

See on Scoop.itVirology News

Circulating RNAs carry messages between the cells of plants and invertebrates. Do they do the same for us?

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PCR: Past, Present, & Future

20 January, 2014

See on Scoop.itVirology News

The Scientist, in collaboration with Biosearch Technologies, invited Kary Mullis to reflect back on these 30 years in terms of his initial discovery, how things stand today, and where he thinks PCR is headed in the future.

Ed Rybicki‘s insight:

I got into PCR sometime in around 1988 – and have since developed amplifications for multicopy genes, virus genes, whole virus genomes, and taught students to do the same.  I have worked with papillomaviruses, HIV, geminiviruses, chicken infectious anaemia virus and potyviruses; my students do PCR for gene assembly and verification of cloned inserts, and do quantitative PCR and cDNA PCR for quantitation of gene expression and assay of virus replication in the presence of inhibitory constructs.

It revolutionised our work more than 30 years ago, and continues to be a fundamental workhorse technique in our labs today.

Viva, PCR, viva!

Kary Mullis – not so much.  The man’s a HIV denialist, or has been, and I have no time for them.

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New HIV report finds big drop in new HIV infections in South Africa

19 January, 2014

See on Scoop.itVirology News

New data show that new HIV infections have been reduced by about a third from 2004 and 2012. The South Africa 2012 HIV Estimates and Projections at-a-glance report was launched in Durban, South Africa on 10 January by the Deputy President of South Africa, Kgalema Motlanthe and UNAIDS Executive Director, Michel Sidibé. Additionally, the Premier of KwaZulu-Natal, Senzo Mchunu launched the Operation Sukuma Sakhe Best Practices Publication at the same event.

There are 6.1 million people living with HIV in South Africa. Since 2009, the government has massively scaled up HIV prevention and treatment programmes. According to the National Department of Health, in 2012, some 2.2 million people were accessing HIV treatment, making it the largest HIV treatment programme in the world. The data show that the number of new HIV infections has dropped from 540 000 new infections in 2004 to 370 000 in 2012.

Ed Rybicki‘s insight:

At last!  We may have passed the peak of the HIV pandemic – at least in SA – at last!!

It’s been a hard road: denialism, activism, the biggest roll-out of ARVs in the world, socially engineering a whole population to change their behaviour – and maybe it’s finally working!

South Africa needs a "viva!"!!

But we’ve still got 6 million-odd people infected with HIV – and they will be around for a while.  Time for therapeutic vaccines!!

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19 January, 2014

See on Scoop.itVirology News

PRETORIA, Jan 19 (NNN-SANEWS) — Primary school girls in South Africa will from this year be immunised against the Human Papilloma Virus (HPV), which causes cervical cancer.

Announcing its launch at Ngidini Primary School in Libode in the Eastern Cape, President Jacob Zuma said government will target girls aged between nine and 12 years of age, through the Integrated School Health Programme.

“The Departments of Basic Education and Health will work closely together in this national programme to protect our girls from this disease.

“Vaccination teams from the Department of Health will visit schools twice a year to ensure that each girl-child receives two doses of the HPV vaccine. We urge parents to cooperate with us and help us succeed in fighting cervical cancer,” said President Zuma.

Cervical cancer graphic by Russell Kightley Media

Ed Rybicki‘s insight:

At last!  South Africa will finally make HPV vaccines available for free to schoolgirls between 9-12 – in preparation for their eventual exposure, via sex, to the viruses that cause cervical cancer.

HPV vaccines are blockbusters for a reason: they are one of only two viral vaccines that will almost certainly prevent cancer developing in a proportion of those who get infected with the viruses in question – which are, of course, HPV and hepatitis B.

And given that most humans have sex, a pretty high percentage of sexually active humans will be exposed to HPV and – to a lesser extent – HBV.

Sex is a normal activity.  Vaccinating against sexually transmitted diseases is therefore a sensible thing to do.  Vaccinating against HPV in a country where over 12% of the population have HIV, is even more sensible – because HIV worsens the effects of HPV.

Vaccination: the sensible thing to do.

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Motsoaledi: Big pharma’s ‘satanic’ plot is genocide

17 January, 2014

See on Scoop.itVirology News

Health minister Aaron Motsoaledi is livid about a pharmaceutical company campaign he says will restrict access to crucial drugs.

Ed Rybicki‘s insight:

Interesting…as an inventor named on a bunch of patents, I should be concerned – but I’m not, because I also believe that people shouldn’t die for want of affordable drugs.

I really, really do.

We have negotiated terms on every licencing deal we have been involved in, that would allow us exclusivity in the African and sometimes other developing world markets – with the intention of ensuring that prices of our product(s) (if any EVER get to market) remain affordable in these regions.

As it is, what the legislation intends to do is to make it more difficult for Big Pharma to extend their patent protection on drugs by simply making changes to formulations, which is a common practice.  I note India is doing the same, and for the same reasons.

Seriously: while companies should receive financial reward for developing drugs, this should not be allowed to continue in perpetuity.

I also don’t think they should be allowed to gouge the market, but that’s another argument.

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