DNA Vaccine 100 Percent Effective Against Rabies In Monkeys

August 03, 1998

Scientists at the Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases (NIAID), have developed a DNA vaccine against rabies that protected eight of eight vaccinated monkeys from the disease. It is the first DNA vaccine to show complete protection in nonhuman primates against a virus that attacks the central nervous system (CNS). Their report describing the successful experiment appears in the August 1998 issue of Nature Medicine.

"There's no gray area in this experiment. That's what's so beautiful about it," comments lead author Donald L. Lodmell, Ph.D., an expert in NIAID's Laboratory of Persistent Viral Diseases located in Hamilton, Mont. In addition to perfect protection afforded by the vaccine, anti-rabies antibodies elicited by the vaccine neutralized a global range of rabies viruses. These results suggest, says Dr. Lodmell, that the DNA vaccine could be effective anywhere in the world.

Each year, more than 40,000 people worldwide die from rabies. It is one of the oldest and most feared human diseases, first described in 2300 B.C. Symptoms include agitation, convulsions, paralysis and delirium. Without prompt treatment, rabies almost inevitably ends in death.

In the United States, few people die from rabies because of widespread immunization of domestic animals: since 1994, only eight deaths have been reported to the Centers for Disease Control and Prevention (CDC). However, the CDC estimates that another 30,000 to 40,000 people each year receive shots to fend off the disease after possible exposure. Rabid bats, raccoons, skunks or other wild animals are the primary sources of human infection in the United States.

Most deaths occur in developing countries where rabies is endemic and resources are inadequate to provide optimal post-exposure treatment. Such treatment, which consists of injections of rabies virus grown in human cells and then inactivated, and human anti-rabies serum, costs about $2,000. Cruder concoctions used in developing countries, derived in animal brains, often cause severe neurological side effects such as allergic encephalitis, which can lead to paralytic reactions as well as death.

"About three years ago," says Dr. Lodmell, "I became very interested in DNA vaccination, and thought it was a logical step for the rabies problem." DNA vaccines are inexpensive, stable and easy to make, and don't need refrigeration, qualities that make feasible the possible widespread use in developing countries.

A postdoctoral fellow in the lab at that time, Nancy B. Ray, Ph.D., made the vaccine from DNA encoding the surface glycoprotein of the rabies virus. After getting excellent immune responses and protection using this vaccine in mice, they decided to move into primates. "The vaccine worked beyond our wildest dreams," says Dr. Lodmell.

They vaccinated eight monkeys with the DNA vaccine, two monkeys with a current human diploid cell vaccine (HDCV) and two control monkeys with the DNA vector alone. All animals received at least one booster shot at 190 days. In all but the two control animals, the researchers could measure high levels of anti-rabies antibodies. Neutralizing antibodies are known to be the primary source of protection for humans and animals.

Dr. Lodmell then had all the monkeys flown to Atlanta, where his collaborators tested the efficacy of the vaccine. At the CDC, Charles E. Rupprecht, D.V.M., Ph.D., chief of the rabies section, and his colleagues exposed the monkeys to lethal doses of rabies virus. By day 11, the two control monkeys had developed clinical signs of the disease. Yet six months after challenge, the investigators still could detect no evidence of rabies virus in the eight monkeys that received the DNA vaccine and the two that received the HDCV vaccine.

The only drawback of the DNA vaccine, says Dr. Lodmell, is that the antibody response cannot be detected before 30 days. Hence, as currently designed, the vaccine would not be suitable for post-exposure prevention of disease. However, he believes researchers will be able to overcome this problem in the future. On the other hand, DNA vaccines typically provide long-lasting immunity, so they could be used prophylactically to protect people at high risk, such as veterinarians and individuals who live in developing countries. Currently, Dr. Lodmell and his colleagues are assessing the durability of the antibody response following just one immunization to investigate the requirement for booster vaccinations, as well as other issues related to protection.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH and CDC are agencies of the U.S. Department of Health and Human Services.
DL Lodmell, NB Ray, MJ Parnell, LC Ewalt, CA Hanlon, JH Shaddock, DS Sanderlin and CE Rupprecht. DNA immunization protects nonhuman primates against rabies virus. Nature Medicine 4(8):949-52 (1998).

Press releases, fact sheets and other NIAID-related materials are available via the NIAID web site at http://www.niaid.nih.gov.

NIH/National Institute of Allergy and Infectious Diseases

Related Vaccine Articles from Brightsurf:

Who should get the COVID-19 vaccine first?
Nineteen global health experts from around the world have proposed a new, three-phase plan for vaccine distribution -- called the Fair Priority Model -- which aims to reduce premature deaths and other irreversible health consequences from COVID-19.

Breakthrough with cancer vaccine
Scientists have developed a new cancer vaccine with the potential to activate the body's immune system to fight a range of cancers, including leukaemia, breast cancer, lung cancer and pancreatic cancers.

How to improve the pneumococcus vaccine
Pneumococcus kills 1 million children annually according to the World Health Organization.

US inroads to better Ebola vaccine
As the world focuses on finding a COVID-19 vaccine, research continues on other potentially catastrophic pandemic diseases, including Ebola and Marburg viruses.

Successful MERS vaccine in mice may hold promise for COVID-19 vaccine
In a new study, published April 7 in mBio, researchers from the University of Iowa and the University of Georgia demonstrate that a new vaccine fully protects mice against a lethal dose of MERS, a close cousin of COVID-19.

Coronavirus Vaccine: Where are we and what's next? (video)
You might have heard that COVID-19 vaccine trials are underway in Seattle.

Why isn't there a vaccine for staph?
A study from Washington University School of Medicine in St.

Exposing vaccine hesitant to real-life pain of diseases makes them more pro-vaccine
New research from Brigham Young University professors finds there is a better way to help increase support for vaccinations: Expose people to the pain and suffering caused by vaccine-preventable diseases instead of trying to combat people with vaccine facts.

Lifetime flu vaccine?
Another year, another flu vaccine because so far scientists haven't managed to make a vaccine that protects against all strains of flu.

On the horizon: An acne vaccine
A new study published in the Journal of Investigative Dermatology reports important steps that have been taken towards the development of an acne vaccine.

Read More: Vaccine News and Vaccine Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.