Building a better Rift Valley fever vaccine

June 27, 2012

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 , blindness, encephalitis and even death on a small percentage of those it infects. It also attacks cattle, sheep and goats, producing high 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 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 Development member Tetsuro Ikegami, lead author of a paper on the vaccine work now online in the . "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 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."

Explore further: New genetically engineered vaccines target Rift Valley fever

Related Stories

New genetically engineered vaccines target Rift Valley fever

August 24, 2011
(PhysOrg.com) -- Researchers from the University of California, Davis, and elsewhere are reporting the development of two genetically engineered vaccines to combat the mosquito-borne Rift Valley fever, devastating to livestock ...

Researchers create new experimental vaccine against chikungunya virus

August 12, 2011
Researchers have developed a new candidate vaccine to protect against chikungunya virus, a mosquito-borne pathogen that produces an intensely painful and often chronic arthritic disease that has stricken millions of people ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.