Featured Research

from universities, journals, and other organizations

Building a better Rift Valley fever vaccine

Date:
June 28, 2012
Source:
University of Texas Medical Branch at Galveston
Summary:
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.

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."

Other authors of the Journal of Virology paper include UTMB postdoctoral fellows Sabarish V. Indran and Terence E. Hill, BSL4 lab manager Terry L. Juelich, Associate Professor Chien-Te K. Tseng, Assistant Professors Bin Gong and Alexander N. Freiberg, and Shuetsu Fukushi and Shigeru Morikawa of the National Institute of Infectious Diseases in Tokyo, Japan. Support for this research was provided by the National Institute of Allergy and Infectious Diseases via the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, as well as UTMB's Sealy Center for Vaccine Development.


Story Source:

The above story is based on materials provided by University of Texas Medical Branch at Galveston. Note: Materials may be edited for content and length.


Journal Reference:

  1. O. Lihoradova, B. Kalveram, S. V. Indran, N. Lokugamage, T. L. Juelich, T. E. Hill, C.-T. K. Tseng, B. Gong, S. Fukushi, S. Morikawa, A. N. Freiberg, T. Ikegami. The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine. Journal of Virology, 2012; 86 (14): 7650 DOI: 10.1128/JVI.00778-12

Cite This Page:

University of Texas Medical Branch at Galveston. "Building a better Rift Valley fever vaccine." ScienceDaily. ScienceDaily, 28 June 2012. <www.sciencedaily.com/releases/2012/06/120628131356.htm>.
University of Texas Medical Branch at Galveston. (2012, June 28). Building a better Rift Valley fever vaccine. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2012/06/120628131356.htm
University of Texas Medical Branch at Galveston. "Building a better Rift Valley fever vaccine." ScienceDaily. www.sciencedaily.com/releases/2012/06/120628131356.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins