Scientists in UK have developed a new method to create an entirely synthetic vaccine which doesn’t rely on using live infectious virus, meaning it is much safer.
The prototype vaccine they have created, for the animal disease foot-and-mouth, has been engineered to make it more stable.
That means it can be kept out of the fridge for many hours before returning to the cold chain – overcoming one of the major hurdles in administering vaccines in the developing world.
The research, published in the journal PLOS pathogens, was collaboration between scientists at Oxford and Reading Universities, the Pirbright Institute, and the UK’s national synchrotron facility, the Diamond Light Source near Oxford.
Scientists in UK have developed a new method to create an entirely synthetic vaccine which doesn’t rely on using live infectious virus, meaning it is much safer
Diamond is a particle accelerator which sends electrons round a giant magnetic ring at near light speeds.
The electrons emit energy in the form of intense X-rays which are channeled along “beamlines” – into laboratories where they are used to analyze structures in extraordinary detail.
Synchrotrons have been used before to analyze viruses at the atomic level, but the technology has advanced considerably to enable scientists to create a stable synthetic vaccine.
“What we have achieved here is close to the holy grail of foot-and-mouth vaccines.
“Unlike traditional vaccines, there is no chance that the empty shell vaccine could revert to an infectious form,” said Dave Stuart, Life Sciences Director at Diamond, and MRC Professor of Structural Biology at the University of Oxford.
“This work will have a broad and enduring impact on vaccine development, and the technology should be transferable to other viruses from the same family, such as poliovirus and hand-foot-and-mouth disease, a human virus which is currently endemic in South-East Asia.”
These human disease threats, like foot-and-mouth, are all picornaviruses.
Viruses are inherently unstable and fragile, but picornaviruses can be studied using X-ray crystallography.
This enables the protein shell of the virus to be analyzed at the atomic level – something a billion times smaller than a pinhead.
As with any vaccine, the aim is to prompt the immune system to recognize this outer shell and destroy the pathogen before it has time to lock onto cells and infect them with its genetic material.
In this research the scientists created a synthetic viral shell, but lacking its pathogenic RNA interior – the genetic material the virus uses to replicate itself.
Crucially they were able to reinforce the structure of the viral shell to make it stronger, to improve the stability of the vaccine.
Pre-clinical trials have shown it to be stable at temperatures up to 56 C for at least two hours. Foot-and-mouth is endemic in central Africa, parts of the Middle East and Asia, so this would be a significant improvement over existing vaccines.
With current foot-and-mouth vaccines it is difficult to distinguish between immunized livestock and those which have been infected.
That proved to be a major hurdle in controlling the foot-and-mouth outbreak in the UK in 2001 because it would have prevented the export of livestock.
The synthetic vaccine should allow scientists to show the absence of infection in vaccinated animals.
“The foot-and-mouth-disease virus epidemic in the UK in 2001 was disastrous and cost the economy billions of pounds in control measures and compensation,” explained Dr. Bryan Charleston, Head of Livestock Viral Diseases Programme at the Pirbright Institute.
“This important work has been a direct result of the additional funding that was provided as a result of the 2001 outbreak to research this highly contagious disease.”
The potential hazards of working with viruses was underlined in 2007 when the Pirbright laboratory site was identified as the source of a leak which led to an outbreak of foot-and-mouth disease.
Polio, another picornavirus, which exclusively affects humans, has been eliminated from nearly every country in the world, although it stubbornly persists in Nigeria, Pakistan and Afghanistan.
The need for secure vaccine production will become even more vital should polio be wiped out.
“Current polio vaccines, which use live virus for their production, pose a potential threat to the long-term success of eradication if they were to re-establish themselves in the population.
“Non-infectious vaccines would clearly provide a safeguard against this risk”, said Dr. Andrew Macadam, a virologist specializing in polio at the National Institute for Biological Standards and Control in Hertfordshire.
“This technology has great potential in terms of cost and biosafety.
“Any design strategy that minimizes the chances of accidental virus release would not only make the world a safer place but would lower the bio-containment barriers to production allowing vaccines to be made more cheaply all over the world.”
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An immediate treatment after HIV infection may be enough to “functionally cure” about a 10th of those diagnosed early, say researchers in France.
The researchers have been analyzing 14 people who stopped therapy, but have since shown no signs of the virus resurging.
It follows reports of a baby girl being effectively cured after very early treatment in the US.
However, most people infected with HIV do not find out until the virus has fully infiltrated the body.
The group of patients, known as the Visconti cohort, all started treatment within 10 weeks of being infected.
They stuck to a course of antiretroviral drugs for three years, on average, but then stopped.
The drugs keep the virus only in check, they cannot eradicate it from its hiding places inside the immune system.
Normally, when the drugs stop, the virus bounces back.
This has not happened in the Visconti patients. Some have been able to control HIV levels for a decade.
An immediate treatment after HIV infection may be enough to functionally cure about a 10th of those diagnosed early
Dr. Asier Saez-Cirion, from the Institute Pasteur in Paris, said: “Most individuals who follow the same treatment will not control the infection, but there are a few of them who will.”He said 5-15% of patients may be functionally cured, meaning they no longer needed drugs, by attacking the virus soon after infection.
“They still have HIV, it is not eradication of HIV, it is a kind of remission of the infection.”
Their latest study, in the journal PLoS Pathogens, analyzed what happened to the immune system of the patients.
Early treatment may limit the number of unassailable HIV hideouts that are formed. However, the researchers said it was “unclear” why only some patients were functionally cured.
However, he cautioned that many patients would be diagnosed much later than in this study.
A new research suggests that the origins of HIV can be traced back millions rather than tens of thousands of years.
HIV, which causes AIDS, emerged in humans in the 20th Century, but scientists have long known that similar viruses in monkeys and apes have existed for much longer.
A genetic study shows HIV-like viruses arose in African monkeys and apes 5 million to 12 million years ago.
The research may one day lead to a better understanding of HIV and AIDS.
The HIV virus affects 34 million people worldwide.
The disease emerged during the 20th century after a HIV like virus jumped from chimps to humans.
Scientists have long known that similar viruses, known as lentiviruses, are widespread in African primates.
Past genetic research has suggested these “cousins” of the HIV-virus arose tens of thousands of years ago, but some experts have suspected this is an underestimate.
Scientists at the University of Washington in Seattle, US, and the Fred Hutchinson Cancer Research Center, also in Seattle, looked at the genetic signatures of HIV-like viruses in a number of primates, including chimps, gorillas, orangutans and macaques.
A genetic study shows HIV-like viruses arose in African monkeys and apes 5 million to 12 million years ago
Changes in genes that have evolved in the immune systems of monkeys and apes in Africa suggest the viruses arose between 5 and 16 million years ago.
The research, published in the journal PLOS Pathogens, gives clues to how the immune systems of our closest relatives evolved to fight infection.
Dr. Michael Emerman of the Fred Hutchinson Cancer Research Center said: “Our study reveals that, while primate lentiviruses may have modern consequences for human health, they have ancient origins in our non-human primate relatives.”
UCLA scientists have found that human stem cells can be genetically engineered into “warrior” cells that fight HIV and the new cells can attack HIV-infected cells inside a living creature.
The breakthrough discovery is hoped to be the first step towards a treatment that can eradicate HIV from an infected patient.
Much HIV research focuses on vaccines or drugs that slow the virus’s progress – but this new technique could offer hope of a “cure”.
The study, published April 12 in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues.
“We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body,” said lead researcher Scott G. Kitchen.
The scientists took CD8 cytotoxic T lymphocytes – the “killer” T cells that help fight infection – from an HIV-infected individual and identified the molecule which guides the T cell in recognizing and killing HIV-infected cells.
Human stem cells can be genetically engineered into “warrior” cells that fight HIV and can attack HIV-infected cells inside a tissue
However, these T cells, while able to destroy HIV-infected cells, do not exist in great enough quantities to clear the virus from the body.
So the researchers cloned the receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.
The engineered stem cells developed into a large population of mature, multi-functional HIV-specific cells that could specifically target cells containing HIV proteins.
The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.
In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates.
They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.
In a series of tests on the mice’s peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 “helper” T cells – which become depleted as a result of HIV infection – increased, while levels of HIV in the blood decreased.
“We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people,” Scott G. Kitchen said.
