Building a better Rift Valley fever vaccine
University of Texas Medical Branch researchers have significantly improved an existing experimental vaccine for Rift Valley fever virus, making possible the development of a more effective defense against the dangerous mosquito-borne pathogen.
The African virus causes fever in humans, inflicting liver damage, blindness, encephalitis and even death on a small percentage of those it infects. It also attacks cattle, sheep and goats, producing high mortality rates in newborn animals and causing spontaneous abortions in nearly all infected pregnant sheep.
In 2000, outbreaks of Rift Valley fever in Yemen and Saudi Arabia showed that the virus could expand beyond its original range. With this and the rapid North American spread of West Nile virus in mind, infectious-disease experts have long feared that Rift Valley fever virus might come to the United States or Europe, causing major human suffering and devastating the livestock industry in affected areas.
"If Rift Valley fever virus were introduced to the U.S. or Europe, it would be a very scary situation," said UTMB assistant professor and Sealy Center for Vaccine Development member Tetsuro Ikegami, lead author of a paper on the vaccine work now online in the Journal of Virology. "To be ready to respond, we want a vaccine that can raise immune response very quickly in large animals and health workers. We also want a vaccine that will allow us to differentiate between infected and vaccinated animals."
Ikegami's first requirement quick response dictated the use of a so-called "live attenuated vaccine." A live attenuated vaccine is a strain of virus that has been weakened to harmlessness, but still has the ability to reproduce and provoke a robust immune response. Such vaccines often require only a single injection, increasing speed and convenience of administration.
A live attenuated vaccine for Rift Valley Fever virus already exists, a strain called MP-12. MP-12 produces a strong immune response in humans and livestock, but human safety trials of the vaccine have never been completed. Practical application of MP-12 faces other obstacles as well. For one thing, researchers worry that the vaccine retains a small amount of residual virulence. For another, they're concerned that the antibodies MP-12 evokes are identical to those produced in response to infection by full-strength Rift Valley fever virus. In an outbreak, public health officials would be unable to tell animals vaccinated with MP-12 from naturally infected ones, making it impossible for them to map the epidemic's spread and respond effectively.
To resolve these issues, Ikegami and his colleagues went to work on MP-12's genome, focusing on a segment designated NSs. When a Rift Valley fever virus enters a cell, NSs produces proteins that function like saboteurs. They attack two of the cell's key defense systems: the genetic mechanism that generates the antiviral protein interferon beta, and a protein called PKR, which suppresses viral protein production.
"We removed the NSs gene because we thought it would attenuate MP-12 further, and it would make it easy to differentiate infected from vaccinated animals MP-12 without NSs wouldn't produce any anti-NSs antibody, thus giving a different antibody response from wild-type Rift Valley fever virus," Ikegami said.
Experiments with mice exposed to Rift Valley fever virus in UTMB's Robert E. Shope, MD Biosafety Level 4 Laboratory confirmed that the NSs-less strain remained a highly effective vaccine. But Ikegami was not satisfied.
"The neutralizing antibody response was slightly decreased, and I thought we could do better if we retained some of the function of the NSs," he said. To do this, the team introduced a gene for a "dominant negative PKR" a molecule that would interfere with the cell-defending PKR protein, allowing the vaccine virus to multiply more freely. When they tested the new vaccine strain in mice, they found that it actually protected the animals better than MP-12.
"We got really good efficacy in mice, and we're hoping it will translate well to large animals," Ikegami said. "This has been a very successful project, with some great teamwork and major contributions from two postdocs, Olga Lihoradova and Birte Kalveram."
Journal reference: Journal of Virology
Provided by University of Texas Medical Branch at Galveston
- New genetically engineered vaccines target Rift Valley fever Aug 24, 2011 | not rated yet | 0
- New vaccine strategies could safely control Rift Valley fever Jun 22, 2010 | not rated yet | 0
- Virus death toll rises in Kenya Jan 26, 2007 | not rated yet | 0
- New West Nile and Japanese encephalitis vaccines produced May 30, 2008 | not rated yet | 0
- Researchers create new experimental vaccine against chikungunya virus Aug 12, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
Medical research 15 minutes ago | not rated yet | 0 |
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
Medical research 37 minutes ago | not rated yet | 0
Every 20 seconds, a limb is lost as a consequence of diabetic foot ulcer that does not heal. To date, medical solutions that can change this situation are very limited. In his doctoral thesis Yue Shen from the Industrial ...
Medical research 5 hours ago | not rated yet | 0
When tumours metastasise, they can block lymphatic vessels, as researchers from ETH Zurich have discovered using a new method. The lymphatic fluid subsequently has to find a new path through the tissue. Such ...
Medical research 5 hours ago | not rated yet | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research 23 hours ago | 5 / 5 (3) | 0 |
A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year ...
59 minutes ago | not rated yet | 0 |
A new report suggests that improved health care and significant reductions in drug costs might be attained by breaking up the age-old relationship between physicians and drug company representatives who promote the newest, ...
1 minute ago | not rated yet | 0
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
37 minutes ago | not rated yet | 0
National guidelines recommend that at-risk women be screened for elevated cholesterol levels to reduce their chances of developing cardiovascular disease. But who is 'at risk?' The results of a study by investigators ...
33 seconds ago | not rated yet | 0
Women are less likely than men to receive care in a trauma center after severe injury, according to a new study of almost 100,000 Canadian patients.
1 hour ago | not rated yet | 0
Over the past few decades, neuroscientists have made much progress in mapping the brain by deciphering the functions of individual neurons that perform very specific tasks, such as recognizing the location ...
3 hours ago | 5 / 5 (3) | 0 |