Archive for the ‘Influenza viruses’ Category

A Short History of the Discovery of Viruses

6 March, 2015

Now much updated, streamlined, added to and otherwise tarted up!  This is the Web version of an iBook, which you can ask me for.

history cover2

Part 1: Filters and Discovery

Part 2: The Ultracentrifuge, Eggs and Flu

Part 3: Phages, Cell Culture and Polio

Part 4: RNA Genomes and Modern Virology

Sidebar 1: The Discovery of Filoviruses

Sidebar 2: Papillomaviruses and Human Cancer

Sidebar 3: Epstein-Barr Virus and Hepatitis B Virus

Sidebar 4: Human Retroviruses and Cancer

Copyright Edward P Rybicki and Russell Kightley, February and March 2015, except where otherwise noted.

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

Ill prepared for an influenza pandemic

18 August, 2014

Over the last 500 years, there have been, on average, three severe influenza pandemics in each century. The most recent pandemic was declared in 2009. Yet despite much investment in public health and many improvements in vaccine production techniques and know-how, the availability of influenza vaccines during this event was far from adequate. Six months into the pandemic, 534 million doses were available, and after one year that number had risen to 1.3 billion — enough for only 8%and 25%, respectively, of the world population. We were lucky that the pandemic declared in 2009 turned out later to be mild and that just one shot of vaccine was sufficient to protect most people. This is not usually the case during a severe influenza pandemic.

 

Source: www.nature.com

"As countries continue to pre-book pandemic supply, it is more and more likely that the limited vaccines available during the first months of any pandemic during the next few years will be sold out almost completely"

And what does everyone think happened in South Africa during most of 2009 and 2010?

Well, they probably don’t – because not that many of them got sick.  But THERE WAS NO VACCINE for the general population until LATE 2010 – when the chances of another round of H1N1pdm 2009 had dissipated due to summer coming on.

And the vaccine that HAD come into the the country in 2010 got used for medical personnel, and – for the 2010 World Cup staff.

Seriously, we need to do better than this – and responding QUICKLY to news of a pandemic would be the ticket.

Using plants B-)

See on Scoop.itVirology News

“Controversial scientist recreates H1N1 flu that killed 500K people” – NOT

2 July, 2014

Dr Yoshihiro Kawaoka, professor of virology at University of Wisconsin at Madison, has tweaked the 2009 strain of pandemic influenza to make it resistant the human immune system’s antibodies.

Source: www.dailymail.co.uk

Trust the Dimwitted Mail to misstate what happened – which is that Yoshihiro Kawaoka selected the H1N1pdm 2009 flu virus in culture till he came up with antibody-binding escape mutants.

What he said:

‘Through selection of immune escape viruses in the laboratory under appropriate containment conditions, we were able to identify the key regions [that] would enable 2009 H1N1 viruses to escape immunity,’

Now recall that the H1N1pdm 2009 virus is NOT a particularly nasty variant; that it has NOT been proved the escape mutants will infect vaccinated people at all – and that all the work was done "a state-of-the-art laboratory at the Institute for Influenza Virus Research in Madison", so the odds that it will get out are VERY low.

But papers have been sold, and the scare is in.

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.

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Legends alive: from left, Fred Murphy; Daan Verwoerd; Bob Millar; Henk Huismans; Errling Norrby; Marc van Regenmortel
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Jean-Marie Andrieu; Marc van Regenmortel – at a VERY good unofficial dinner

20140131-120211.jpg

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

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.

Image

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-)

A Brief History of Influenza

5 April, 2013

See on Scoop.itVirology News

I am TRYING to write an eBook on influenza, which stubbornly refuses to be finished – as part of a sabbatical project, which finished in December 2010.  So, like my History of Virology, I am triall…

Ed Rybicki‘s insight:

I will reprise this post, given a considerable recent spike in interest in it as the new H7N9 Shanghai bird flu starts.  Hopefully to fizzle out, but you never know….

Incidentally, I have an almost-finished iBook (for iPad) on influenza: the first five respondents to this post can trial it for free!

See on rybicki.wordpress.com

PLOS Pathogens: Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

18 March, 2013

See on Scoop.itVirology News

Human influenza infections exhibit a strong seasonal cycle in temperate regions. Recent laboratory and epidemiological evidence suggests that low specific humidity conditions facilitate the airborne survival and transmission of the influenza virus in temperate regions, resulting in annual winter epidemics. However, this relationship is unlikely to account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season. We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally. We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: “cold-dry” and “humid-rainy”. For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11–12 g/kg and 18–21°C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month. These findings provide a simple climate-based model rooted in empirical data that accounts for the diversity of seasonal influenza patterns observed across temperate, subtropical and tropical climates.

Ed Rybicki‘s insight:

This is really quite a big deal: I blogged recently on the first paper that explored this notion in detail; here we see that paper vindicated, and new data presented.

 

It is interesting that the virus should have evolved to be spread in this way: in drier cold air in temperate climates, and in warm wet air in more tropical climes.  It also very nicely explains seasonality in influenza transmission.

 

Now, let’s do something ABOUT it!

See on www.plospathogens.org

ViroBlogy: 2012 in review

1 February, 2013

So: thank you, anyone who clicked in, and regular visitors.  You make it worthwhile!!

The WordPress.com stats helper monkeys prepared a 2012 annual report for this blog.

Here’s an excerpt:

4,329 films were submitted to the 2012 Cannes Film Festival. This blog had 33,000 views in 2012. If each view were a film, this blog would power 8 Film Festivals

Click here to see the complete report.

Virus-like particle and Nano-particle vaccines 2012: a conference report

30 January, 2013

Alta van Zyl, Virology Group, Molecular & Cell Biology Department, UCT

Introduction:

VLP flusm

Haemagglutinin-only Influenza A virus VLP. Courtesy of Russell Kightley Media

The new international conference on virus-like particles and nano-particles (VLPNPV) took place in Cannes, France at The Novotel Montfleury Hotel from the 28th to the 30th of November 2012.  The scope of the conference included virus-like particles (VLPs), the plant-based expression of VLP vaccines as well as expression and optimisation of VLPs.

Other topics included in the conference were:

  • VLP platform delivery systems
  • VLP vaccines
  • Nano-particles and nano-particulate vaccines

A multitude of topics were covered during the conference and many of the talks pertained to the immunogenicity of the VLPs and nano-particles and how they compared with the immunogenicity of DNA or subunit vaccines.

Talks were given by researchers from companies such as Medicago, Mucosis, Pevion Vaccines and Novavax. These talks gave a perspective on factors that need to be considered when commercialising VLP/nano-particle vaccines and to be GMP compliant.

Compelling presentations:

Developing plant-made virus-like particle vaccine products: An integrated platform from discovery to commercial scale

Marc-Andre D’Aoust, Nathalie Landry, Sonia Trepanier, Michele Dargis, Manon Couture and Louis-Philippe Vezina (Medicago, Quebec City, Quebec, Canada)

This talk was about a plant-made VLP against both pandemic and seasonal influenza- these vaccines are now in the clinical trial phase. What was especially interesting was the view from an industry point of view where expression had to be scaled up to produce large amounts of vaccine.  The Medicago platform can synthesize and clone approximately 100 gene constructs in two weeks, they can prepare 100 bacterial cultures per week and they have automated infiltration where 200 plant transformations can be performed per day and 150 VLP engineering approaches can be tested in one week.  For influenza Medicago tested 48 different infiltration approaches in one day for HA, NA, M1, M2 as well as P1 Gag and HGalT.  Medicago has been able to produce 10 million doses of HA VLPs in just one month.

See also: 

  • D’Aoust et al (2010) PBJ 8:  607-619 – The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza.
  • http://www.medicago.com

Development of RNA-free plant VLPs a source of novel therapeutics

George Lomonossoff (John Innes Centre, Norwich, UK)

This group made empty Cowpea Mosaic Virus (CPMV) VLPs that contained no RNA.  CPMV VLPs are versatile nanoparticles to which organic, inorganic and biological molecules can be bound.  The empty nature of the particle means that they can be used as carrier molecules for therapies; this could prove to be potentially useful as a cancer-treatment therapy.  The system is advantageous because of the lack of RNA which makes the particles non-infectious and no bio-containment is needed for the production of these VLPs.

Immunogenicity of VLPs: an immunological perspective

Martin Bachmann (University of Zurich, Zurich, Switzerland)

Background was given from immunological point of view about what makes VLPs so immunogenic. Three properties contribute to the immunological properties of VLPs (1) their size, (2) the repetitiveness of the particle capsid which provides multiple sites for antibody binding and (3) TLR ligands – the particle can be disassembled, the RNA removed and replaced with a TLR ligand to enhance immunogenicity. Also, the size of VLPs is optimal for drainage to the lymph nodes.

Immunogenicity optimization strategies for public-sector development of vaccines: the critical role of optimizing the antigen.

Martin Howell Friede (WHO, Geneva, Switzerland)

This talk was about looking at VLPs from the vaccine development view.  Monomeric antigens are not very immunogenic; therefore adjuvants were developed and came into use. For an efficient vaccine the antigen must be multimeric as antigen alone is insufficient to be immunogenic without adjuvant. Two factors have to be considered when producing a vaccine for FDA approval; (1) optimise the antigen before using an adjuvant, (2) use an adjuvant that has already been approved by the FDA. VLPs as vaccines provide the potential for immune-stimulation without the addition of adjuvant as the multimeric presentation of the antigen will enhance its immunogenicity.

Enhancing the immunogenicity of VLP vaccines

Richard W. Compans (Emory University, Atlanta, Georgia, USA)

This talk highlighted strategies which could be used to enhance the immunogenicity of VLPs.

  1. Look at alternate routes for vaccine delivery (intranasal, intramuscular, subcutaneous etc)
  2. Increase the breadth of immunity by enhancing responses to conserved antigens/epitopes
  3. Increase the amount of antigen incorporated into VLPs
  4. Incorporate the adjuvant into the VLPs as part of the structure

See also:

  • Ye et al (2011) PLoS One 6(5):  e14813
  • Wang et al (2008) J Virol

Innate and adaptive responses to plant-made VLP vaccines

Brian Ward (McGill University, Montreal, Quebec, Canada)

Brain Ward is also the medical officer at Medicago.  Humans rarely react to plant proteins/antigens. The plant glycans fucose/xylose at the N-terminal is an allergen and can cause anaphylaxis in humans. During trial experiments with influenza no individuals developed IgE responses to plant glycans, therefore plant produced vaccine is safe. The H1 VLP induced long lasting memory multifunctional T-cell responses in humans.

Impressions of the conference:

The conference was well organised with leaders in the field presenting their work. Interaction with the delegates aid in building crucial networking opportunities and work relationships. The international arena is packed with new technology development allowing us the opportunity to learn and improve our own understanding of various concepts.

This conference proved to be an invaluable learning experience and I thank the NRF for this opportunity and for providing me with the funding to attend this conference.  The exposure to conferences, especially those in the international arena, aid in the development of students and contribute to the quality of research that is conducted at UCT.

References:

1. VLPNPV website

(http://www.meetingsmanagement.co.uk/index.php?option=com_content&view=article&id=33&Itemid=83)

2.  Personal notes taken at the conference


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