Pirbright Institute grants a new licence for FMDV vaccine development

The Pirbright Institute and its research partners have granted MSD Animal Health an exclusive commercial licence for a new, effective and affordable vaccine to protect livestock against several serotypes of foot-and-mouth disease virus (FMDV). The new vaccine is more stable than current foot-and-mouth disease (FMD) vaccines and is less reliant on a cold-chain during vaccine distribution – characteristics that give the vaccine greater potential for helping to relieve the burden placed on regions where the disease is endemic in large parts of Africa, the Middle East and Asia. These developments have been possible, thanks to a long-standing collaboration between Diamond Light Source, Pirbright, the University of Oxford, the University of Reading and MSD Animal Health, and the vaccine has been developed over the years from basic science to animal trials. This work has been supported by funding from the Wellcome Trust to speed up commercialisation.

Professor David Stuart, Life Sciences Director at Diamond Light Source and MRC Professor in Structural Biology at the University of Oxford, noted:

We have been working to achieve something close to the holy grail of vaccines. Instead of traditional methods of vaccine development, using infectious virus as its basis, our team synthetically created empty protein shells to imitate the protein coat that forms the strong outer layer of the virus. Diamond’s visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, enabled us to visualise in detail something invisible in a normal microscope and to enhance the design, atom by atom, of the empty shells. The key thing is that unlike the traditional FMDV vaccines, there is no chance that the empty shell vaccine could revert to an infectious form. The licence that has just been granted suggests that the work will have a broad and enduring impact on vaccine development.

>Read more on the Diamond Light Source website

Understanding the viruses that kill cancer cells

Taking inspiration from virology to find better treatments for cancer

There are some viruses, called oncolytic viruses, that can be trained to target and kill cancer cells. Scientists in the field of oncolytics want to engineer these viruses to make them safer and more effective so they can be used to treat more people and different types of cancers. To achieve this, they first have to fully understand at the molecular level all the different ways that the virus has evolved to infect healthy cells and cause disease. A research team from Cardiff University set out to better understand how a protein on the surface of a virus often used to kill cancer, called an adenovirus, binds to human cells to cause an infection. Using X-ray crystallography, the team was able to determine the structure of one the key adenovirus proteins. Using this information and after extensive computational analysis, the research team realised the virus was not binding the receptor on the cells that was originally thought. This has important implications for the development of new virotherapies and engineering of viruses to treat cancer. The more thoroughly the researchers can understand how the adenoviruses interact with cancer cells at the molecular level, the more safe and effective treatments can be brought to clinical trial in the future.

>Read more on the Diamond Light Source website

New possibilities against the HIV epidemic

Research identifies new antibodies with potent activity against virus and infected cells

The Human Immunodeficiency Virus type-1 (HIV-1) currently infects 37 million people worldwide, with an additional 2 million new infections each year. Following infection, the virus has a long period of latency, during which it multiplies without causing symptoms. HIV attacks the cells of the immune system, especially the cells called CD4+ T-lymphocytes, which are responsible for triggering the body’s response chain against infections. Thus, by suppressing the action of the immune system, the virus destroys the body’s ability to defend itself against other diseases, leading to the so-called Acquired Immunodeficiency Syndrome, or AIDS.
Even with the development of antiretroviral therapies that have improved quality of life and increased the life expectancy of patients with HIV/AIDS, it is widely accepted that the only way to effectively curb this devastating epidemic is through the development of an HIV-1 vaccine.

>Read more on the Brazilian Synchrotron Light Laboratory website

Image: Part of the structure of the CAP228-16H protein with the region of the V2 loop highlighted in yellow. (Full image here)

Secrets of the deadly white-tail virus revealed

The inner workings of a lethal giant freshwater prawn virus have been revealed by an international team of researchers using data gathered at Diamond Light Source. The results reveal a possible new class of virus and presents the prospect of tackling a disease that can devastate prawn farms around the world.

The detailed structure of a virus that can devastate valuable freshwater prawn fisheries has been revealed by an international team using image data collected in the Electron Bio-Imaging Centre (eBIC) based at Diamond Light Source. The researchers produced high-resolution images of virus like particles, VLP’s, composed of virus shell proteins which they compared with lower resolution images of the complete virus purified from prawn larvae. They found strong similarities between the two suggesting that the more detailed VLP images are a good representation of the intact virus. This research, exposing the inner workings of the MrNV, could make it easier to develop ways of combating the economically important disease, but also suggests that it belongs in a new, separate, group of nodaviruses.
The researchers used the rapidly developing technique of cryo-electron microscopy, cryoEM, which has the ability to produce very high-resolution images of frozen virus particles. Images so detailed that the positions of individual atoms could be inferred. Recent breakthroughs in this technique have transformed the study of relatively large biological complexes like viruses allowing researchers to determine their structures comparatively quickly. The data to produce the MrNV structure described here was captured in two days at the eBIC facility.

>Read more on the Diamond Light Source website

Image: 3D model of the MrNV
Credit: Dr David Bhella

Insights into an antibody directed against dengue virus

We are one step further to uncovering a new way to stave off dengue fever thanks to important work carried out at the I02 beamline at Diamond Light Source.

The study, recently published in Nature Immunology, describes how an antibody effectively targets the dengue virus.
Dengue virus affects hundreds of millions of people worldwide and is an untreatable infection. Secondary infections with dengue can lead to a life-threatening form of the disease due to a phenomenon called antibody-dependent enhancement (ADE). Additionally, efforts to develop a vaccine against the virus have been hindered by ADE.

A huge collaborative effort sought to investigate ADE in dengue, and two antibodies were characterised that bound to the envelope protein of the dengue virus. One of the antibodies was found to be a potent neutraliser of the virus, but importantly was unable to promote ADE.

>Read more on the Diamond Light Source website

Image: Fab binding in the context of the mature virion. e, Comparison of 2C8 Fab and 3H5 Fab docked onto a E dimer. 2C8 (green) and 3H5 (orange) Fabs were docked onto PDB ID 3J27 by aligning the EDIII potion of the structures. The Fabs are shown as surfaces and the E dimer is displayed in cartoon representation. A side view is of the E dimer on the viral surface is shown. The approximate location of the viral membrane is shown schematically.

 

Snaphot of molecular mechanism at work in lethal virus

X-ray crystallography at the Australian Synchrotron contributed to major research findings.

Data collected on the macromolecular crystallography beamlines at the Australian Synchrotron has contributed to major research findings on two deadly viruses, Hendra and Nipah, found in Australia, Asia and Africa. The viruses can be transmitted to humans not directly by the bat which is the natural carrier but by an infected animal like horses or pigs.

Beamline scientist, Dr David Aragao (pictured above), a co-author on the paper in Nature Communications, said that obtaining a clear motion picture of key biological process at the molecular level of viruses is often not available with current biomedical techniques.
“However, using X-ray crystallography from data collected on both MX1 and MX2 beamlines at the Australian Synchrotron, we were able to obtain  8  ‘photograph-like’ snapshots of the molecular process that allows the Hendra and Nipah virus to replicate.“

Two authors of the paper, PhD students Kate Smith and Sofiya Tsimbalyuk, who are co-supervised by Aragao and his collaborator Professor of Biochemistry Jade Forwood of the Graham Centre for Agricultural Innovation Charles Sturt University, used the Synchrotron extensively collecting multiple data sets that required extensive refinements over two years to isolate the mechanism of interest.

>Read more on the Australian Synchrotron website

Image: Beamline scientist, Dr David Aragao.

Respiratory virus study points to likely vaccine target

Scientists develop sugar-coated nanosheets to target pathogens

Molecular Foundry-designed 2-D sheets mimic the surface of cells

Researchers have developed a process for creating ultrathin, self-assembling sheets of synthetic materials that can function like designer flypaper in selectively binding with viruses, bacteria, and other pathogens.
In this way the new platform, developed by a team led by scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), could potentially be used to inactivate or detect pathogens.

The team, which also included researchers from New York University, created the synthesized nanosheets at Berkeley Lab’s Molecular Foundry, a nanoscale science center, out of self-assembling, bio-inspired polymers known as peptoids. The study was published earlier this month in the journal ACS Nano.
The sheets were designed to present simple sugars in a patterned way along their surfaces, and these sugars, in turn, were demonstrated to selectively bind with several proteins, including one associated with the Shiga toxin, which causes dysentery. Because the outside of our cells are flat and covered with sugars, these 2-D nanosheets can effectively mimic cell surfaces.

>Read more on the Advanced Light Source website

Image: A molecular model of a peptoid nanosheet shows loop structures in sugars (orange) that bind to the Shiga toxin (shown as a five-color bound structure at upper right).
Credit: Berkeley Lab

The search for an Ebola vaccine

Researchers expertly solved the crystal structures of drugs bound to the outer coating of the Ebola virus to pinpoint the regions that are essential for inhibitory activity.

Ebola is a viral disease that is highly infectious and associated with a high risk of death. It first arose in 1976, from which point it was associated with dozens of small-scale outbreaks; however, in 2013 Ebola was responsible for a huge epidemic in West Africa. Emergency was declared and over 11,000 people lost their lives to the virus. Despite this horrific state of affairs, Ebola still remains an untreatable disease and there is no vaccine to prevent infection.

>Read more on the Diamond Light Source website

 

World Polio Day

Are we nearing the end of the war on polio?

There was a time when the word itself was enough to strike fear into the hearts of people around the world. Polio: a highly infectious virus that could shatter young lives in the blink of an eye. On the 24th of October, we mark World Polio Day, and this is something worth celebrating. Because whilst the story isn’t over yet, it may well be nearing its end.

Polio has been around since before records began, but it wasn’t until the early-twentieth century that epidemics began to sweep through communities in Europe and America, affecting many thousands of children and families.

It’s hard to underestimate the terror once caused by polio. At its height in the 1950s, parents routinely lived in fear of their children becoming quarantined, paralysed or even worse. It was a dark time in medical history but, despite this, polio really is a success story for modern science.

Molecular Movie

Researchers Create Molecular Movie of Virus Preparing to Infect Healthy Cells

With SLAC’s X-ray laser, scientists captured a virus changing shape and rearranging its genome to invade a cell.

A research team has created for the first time a movie with nanoscale resolution of the three-dimensional changes a virus undergoes as it prepares to infect a healthy cell. The scientists analyzed thousands of individual snapshots from intense X-ray flashes, capturing the process in an experiment at the Department of Energy’s SLAC National Accelerator Laboratory.

>Read More

From Community to Molecule – on Track Towards a Zika Vaccine

A potent new weapon against the Zika virus in the blood of people who have been infected by it.

A research team based at The Rockefeller University has identified a potent new weapon against the Zika virus in the blood of people who have been infected by it. This discovery could lead to new ways of fighting the disease. Detailed examination of the interaction between the virus and antibodies derived from human subjects in Brazil and Mexico, including crystallographic studies performed at the Stanford Synchrotron Radiation Lightsourse (SSRL), have revealed a new potential strategy for developing a vaccine towards this virus.

Through collaborators working in Pau da Lima, Brazil, and Santa Maria Mixtequilla, Mexico, the research team obtained blood samples from more than 400 people, collected shortly after Zika was circulating.

In these samples, antibodies that block the virus from initiating an infection were found. Interestingly, the antibodies appeared to have been initially generated in response to an earlier infection by a related virus (DENV1) that causes dengue fever. It appears that, much like a vaccine, the DENV1 virus can prime the immune system to respond to Zika.