DNA Vaccine Techniques Show Promise Against Rift Valley Fever

June 24, 2010 Anonymous

Magnified approximately 34,000x, this transmission electron micrograph (TEM) depicted a tissue section that had been infected with Rift Valley fever (RVF) virus. CDC / F. A. Murphy; J. DalrympleThough not well known in the United States, Rift Valley fever (RVF) is a dangerous viral disease that is a major cause for concern in Africa. RVF primarily affects animals and can infect several species, including cattle, sheep, goats and camels. Protecting animals from the virus is extremely important in farming, as it has a high death rate for some animals of a particular age (up to 90% for lambs) and can cause a near-100% abortion rate among pregnant ewes. These losses can be devastating for those who raise livestock.

Rift Valley fever is also a concern, however, because it can sometimes infect humans. This typically occurs through contact with infected animals, but the virus can also be spread by the bite of infected mosquitoes or blood-feeding flies. Some evidence suggests that humans can even be infected by drinking unpasteurized or uncooked milk from infected animals.

Typically a human infection with RVF is mild and passes without treatment, but there are three more serious forms of the disease: one that leads to retinal lesions (and possible blindness); one that leads to meningoencephalitis and leaves the victim vulnerable to residual neurological problems; and one that leads to haemorrhagic fever, with a death rate as high as 50%. Prior to 1997 the disease had been limited to Sub-Saharan regions, but outbreaks have since occurred in Saudi Arabia, Mauritania, Egypt and Yemen, and outbreaks in Kenya, Somalia and Tanzania from 2006-2007 led to human deaths, raising concern that the virus could continue to spread. The United States federal government has also classified RVF as a potential biowarfare threat.

Developing a vaccine for human use against Rift Valley fever has been challenging to this point, particularly because of concerns that adverse side effects from live attenuated RVF vaccines might limit their use. Inactivated vaccines, while typically safer, often require multiple doses and “boosters” to maintain immunity. Now, however, researchers at the University of Pittsburgh Center for Vaccine Research have used newer approaches to develop experimental vaccines, and demonstrated that the vaccines produce strong immune responses in mice.

Working with colleagues from the University of North Carolina, the Pitt researchers developed DNA vaccines against RVF, using an altered segment of an inactivated virus. Because DNA vaccines have sometimes been less effective than expected in human clinical trials, the researchers included what they called a “molecular adjuvant” in one vaccine–a particular protein to provoke an antibody response specific to the Rift Valley fever virus.

They vaccinated separate groups of mice with both of their experimental vaccines (one with the protein, one without) as well as with a live attenuated vaccine. Mice vaccinated with the DNA vaccine using the complement protein had more antibodies that neutralize pathogens than the mice who received the vaccine without the protein. Although the study was limited to mice and additional research must be done, the researchers suggest that these vaccine strategies may prove safer for human use than live attenuated vaccines.

Source and additional information:

Bhardwaj N, Heise MT, Ross TM, 2010 Vaccination with DNA Plasmids Expressing Gn Coupled to C3d or Alphavirus Replicons Expressing Gn Protects Mice against Rift Valley Fever Virus. PLoS Negl Trop Dis 4(6): e725. doi:10.1371/journal.pntd.0000725
Link to article: http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000725

Rift Valley fever Fact Sheet. World Health Organization, revised May 2010.
Link to fact sheet: http://www.who.int/mediacentre/factsheets/fs207/en/

Nierengarten and Lutwick. Biowarfare Vaccines: Rift Valley Fever. Medscape Infectious Diseases. 2002;4(2)
Link to article: http://www.medscape.com/viewarticle/439044_2