Research yields insights into deadly nature of 1918 flu pandemic

Brussels, 18 October 2006

By Charlene Porter
Washington File Staff Writer

Scientists at the National Institute for Allergy and Infectious Diseases (NIAID) have developed a vaccine that protects mice from a flu strain that killed up to 50 million people in 1918-1919.

The finding is important in helping 21st century researchers understand the lethal power of the H1N1 virus that caused the most deadly influenza pandemic in history. That finding is a step toward understanding the mechanics of any virus capable of setting off a pandemic and devising ways to stop the process, according to an October 17 NIAID press release.

"A key to containing pandemic flu viruses is to understand their vulnerabilities and determine whether they can evade immune recognition," said Dr.. Gary J. Nabel, director of NIAID's Vaccine Research Center where the experimental vaccines were developed. "What we learn about the H1N1 virus that caused the 1918 pandemic is pertinent to other pandemic viruses and to the development of effective and universal vaccines."

The work is an advance upon a 2005 breakthrough made by U.S. scientists when they reconstructed the 1918 Spanish flu virus and identified the characteristics of the flu strain that made it so lethal. (See related article.)

Using the genetic sequence information that emerged from that work, the researchers created plasmids -- small strands of DNA designed to express specific characteristics -- carrying genes for the virus' hemagglutinin (HA) protein, the surface protein found in all flu viruses that allows the virus to stick to a cell and cause infection.

The team developed a vaccine that contained two types of plasmids -- one with the HA protein like the 1918 strain, and one with an altered HA protein that would weaken the virus.

The work of administering the vaccine to laboratory mice and monitoring their progress moved to the U.S. Centers for Disease Control and Prevention (CDC) to be conducted in its specialized, highly secure, biosafety labs, used in experimentation with contagious and potentially deadly materials.

After dosing the mice with the vaccine, the researchers found significant responses both in terms of production of T-Cells, the white blood cells critical in mustering the body's immunity against viruses, and in the production of neutralizing antibodies.

CDC's Terrence Tumpey found that all 10 mice injected with the experimental vaccine survived.

The research went further to test the antibodies from the immunized mice by injecting them in nonimmunized mice. They found the nonimmunized mice developed antibody levels only slightly lower than the animals that had been vaccinated.

The research then exposed the antibody-treated mice to the 1918 viral strain and found that eight out of 10 of the animals survived.

NIAID is a component of the National Institutes of Health, and has been exploring a variety of research paths to better prepare the nation and the world for the potential development of pandemic influenza. (See related article.)

LATEST DEATHS

Indonesia's Ministry of Health has reported three human deaths from the H5N1 avian influenza virus, as confirmed by the World Health Organization in a situation update issued October 16.

One case involved a 67-year-old woman from West Java Province, and a second involved an 11-year-old male from South Jakarta. In both these unrelated cases, the victims reportedly had contact with sick or dying chickens around their households or neighborhoods.

The H5N1 virus has caused the deaths of more than 200 million birds, either by death or destruction. This highly pathogenic form of avian influenza is considered endemic in Asia, but also has spread to more than 50 nations as far away as Europe and Africa.

The third case reported October 16 involved a -year-old female from Central Java who was stricken with symptoms and died within only five days. The source of her exposure to the virus is being investigated.

Indonesia has experienced more human cases of illness and death from H5N1 than any other country in 2006. In the three years since the disease first started appearing in humans, Indonesia has confirmed a total of 72 cases, resulting in 55 fatalities.

Human cases have occurred in 10 countries, resulting in 151 deaths, the vast majority of which have been traced to viral exposure through sick or dying chickens, their body fluids, or environment. Although a handful of human cases appear to have resulted from transmission between humans, the virus is not considered contagious among humans.

Health experts warn that if the virus were to mutate and develop that capability, a global pandemic could result with the potential for widespread death and social and economic disruption.

The United States has invested almost $400 million in the international effort to control and contain avian influenza to help stave off a human pandemic. (See fact sheet.)

For ongoing coverage of the disease and efforts to combat it, see Bird Flu (Avian Influenza).