Yenra : Safety : West Nile Virus Vaccine : Experimental DNA vaccine based on gene sequence

Vical Incorporated announced today that the company has been requested to manufacture clinical-grade supplies of an experimental DNA vaccine against the West Nile Virus for development planned by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). The new West Nile Virus vaccine manufacturing agreement is in addition to Vical's large-scale DNA vaccine manufacturing subcontract announced in May 2003, and Vical's Ebola DNA vaccine manufacturing subcontract announced in July 2002; all of the contracts are issued and managed on behalf of NIAID's Vaccine Research Center by SAIC Frederick, Inc. under the umbrella of a federally funded prime contract with NIH.

Vical's President and Chief Executive Officer, Vijay B. Samant, said, "Vical's DNA delivery technology offers a unique opportunity to shorten vaccine development timelines. The 'plug and play' nature of our gene delivery method allows rapid evaluation of candidate immunogens, which can cut years from the total vaccine development cycle. We already have begun production of the West Nile Virus vaccine under this new agreement. Another benefit of using Vical's technology platform for such virulent agents is that development and production of vaccines do not involve any handling of the pathogen itself. These speed and safety advantages are extremely important for emerging diseases such as West Nile Virus, Ebola, SARS and others, which can spread rapidly if unchecked by either natural or conferred immunity. DNA vaccines for a wide variety of infectious diseases are under development by Vical, its licensees, and others.

"Through this collaboration, our technology has the potential to yield the first approvable human vaccine for West Nile Virus. The vaccine construct incorporates West Nile Virus gene sequences known to be immunogenic. We are pleased to apply our expertise and manufacturing resources in support of the VRC's West Nile Virus vaccine program, and we look forward to the development of an effective vaccine against this emerging disease."

West Nile Virus has been an increasing seasonal threat in the United States over the past several years, causing growing numbers of cases and deaths in birds, horses, and humans each summer. The disease is spread by many species of mosquitoes, which carry the virus from host to host. Most infected people have no disease symptoms, and some have only mild symptoms. But approximately one out of every 150 infected people develops serious disease symptoms of the central nervous system, including headache, high fever, tremors, convulsions, numbness, vision loss, coma, and paralysis lasting several days to several weeks, potentially with some permanent neurological damage. Most West Nile Virus deaths are caused by encephalitis, a severe swelling of the brain, or meningitis, a severe swelling of the membrane surrounding the brain and spinal cord.

Conventional vaccines, using whole killed West Nile Virus, are available for horses and for some species of birds. To develop a human vaccine using this approach, however, could require many years of further development and testing to provide sufficient proof of safety and effectiveness.

Vical researches and develops biopharmaceutical products based on our patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of our DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. We have retained all rights to our internally developed product candidates. In addition, we collaborate with major pharmaceutical companies and biotechnology companies that give us access to complementary technologies or greater resources. These strategic partnerships provide us with mutually beneficial opportunities to expand our product pipeline and serve significant unmet medical needs.

West Nile FAQ

Q. How do people get West Nile encephalitis?

A. By the bite of a mosquito (primarily one of the Culex species) that is infected with West Nile virus.

Q. What is the basic transmission cycle?
A. Mosquitoes become infected when they feed on infected birds, which may circulate the virus in their blood for a few days. After an incubation period of 10 days to 2 weeks, infected mosquitoes can then transmit West Nile virus to humans and animals while biting to take blood. The virus is located in the mosquito's salivary glands. During blood feeding, the virus is may be injected into the animal or human, where it may multiply, possibly causing illness.

Q. Can you get West Nile encephalitis from another person?

A. No. West Nile encephalitis is NOT transmitted from person-to-person. For example, you cannot get West Nile virus from touching or kissing a person who has the disease, or from a health care worker who has treated someone with the disease.

Q. Can you get West Nile virus directly from birds?
A. There is no evidence that a person can get the virus from handling live or dead infected birds. However, avoid bare-handed contact when handling any dead animals, including dead birds. Use gloves or double plastic bags to place the carcass in a garbage can.

Q. Besides mosquitoes, can you get West Nile virus directly from other insects or ticks?
A. Infected mosquitoes are the primary source for West Nile virus and caused the recent outbreak in the New York City metropolitan area. Ticks infected with West Nile virus have been found in Asia and Africa. Their role in the transmission and maintenance of the virus is uncertain. However, there is no information to suggest that ticks played any role in the New York area outbreak.

Q. Where did West Nile virus come from?
A. West Nile virus has been commonly found in humans and birds and other vertebrates in Africa, Eastern Europe, West Asia, and the Middle East, but has not previously been documented in the Western Hemisphere. It is not known from where the U.S. virus originated, but it is most closely related genetically to strains found in the Middle East.

Q. What are the symptoms of West Nile encephalitis?
A. Most infections are mild and symptoms include fever, headache, and body aches, often with skin rash and swollen lymph glands. More severe infection may be marked by headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, paralysis and, rarely, death.

Q. Is a woman's pregnancy at risk if she gets West Nile encephalitis?
A. There is no documented evidence that a pregnancy is at risk due to infection with West Nile virus.

Q. How is West Nile encephalitis treated?
A. There is no specific therapy. In more severe cases, intensive supportive therapy is indicated, i.e., hospitalization, intravenous (IV) fluids, airway management, respiratory support (ventilator) if needed, prevention of secondary infections (pneumonia, urinary tract, etc.), and good nursing care.

Q. Is there a vaccine against West Nile encephalitis?
A. No.

Q. What is the incubation period in humans (i.e., time from infection to onset of disease symptoms) for West Nile encephalitis?
A. Usually 3 to 15 days.

Q. What should I do if I think I have West Nile encephalitis?
A. Seek medical care as soon as possible.

Q. Reference was made to "West Nile-like" virus. Does this mean the virus found in New York is not West Nile virus?
A. Initially, the virus found in New York was identified as being genetically related to West Nile virus. Genetic sequencing of virus found in the New York area is now complete. The virus has been definitively identified as West Nile virus.

Q. Who is at risk for getting West Nile encephalitis?
A. All residents of areas where virus activity has been identified are at risk of getting West Nile encephalitis; persons greater than 50 years of age have the highest risk of severe disease.

Q. When did the 1999 outbreak in New York end?
A. The risk for infection in the New York City area ended when mosquito activity ceased for the season, i.e., when sustained freezing temperatures occurred.

Q. What precautions need to be taken to prevent a recurrent outbreak?
A. Active sampling for West Nile virus (i.e., surveillance) in mosquito and bird populations will greatly enhance state and local government's early detection systems. When the first virus activity is detected in a community, prior to the occurrence of human disease, rapid mosquito control measures, such as targeted application of adulticides and larvacides, should be implemented.

Q. I understand West Nile virus was found in "overwintering" mosquitoes in the New York City area in early 2000. What does this mean?
A. Culex species of mosquitoes survive through the winter, or overwinter, in the adult stage. This finding means that the virus survived along with the mosquitoes and may still be present in the area where the mosquitoes were found. State and local mosquito surveillance programs will provide timely information about West Nile virus activity in the New York City area, and control programs to reduce mosquito densities, if necessary.

Q. Do the findings indicate that West Nile virus is established in the Western Hemisphere? It is too early to speculate about the permanent establishment of West Nile virus. Continued surveillance will assist in answering this question.

Q. What proportion of people die when infected with West Nile virus?
A. Case-fatality rates range from 3% to 15% and are highest in the elderly.

Q. How does West Nile virus actually cause death in humans?
A. Following transmission by an infected mosquito, West Nile virus multiples in the person's blood system and crosses the blood-brain barrier to reach the brain. The virus interferes with normal central nervous system functioning and causes inflammation of brain tissue.

Q. How many cases of West Nile encephalitis occurred in the U.S. in 1999?
A. Prior to August 1999, West Nile virus had never been reported in the U.S. In 1999, 62 cases of severe disease, including 7 deaths, occurred in the New York area. No reliable estimates are available for the number of cases of West Nile encephalitis that occur worldwide.

Q. Is the disease seasonal in its occurrence?
A. In the temperate zone of the world (i.e., between latitudes 23.5° and 66.5° north and south), West Nile encephalitis cases occur primarily in the late summer or early fall. In the southern climates where temperatures are milder, West Nile virus can be transmitted year round.

Q. Do wild birds infected with West Nile virus die or become ill?
A. In the New York area epidemic there was a large die-off of American crows. A total of 18 native bird species have demonstrated morbidity or mortality. Also, domestic geese were reported as dying from West Nile virus infection in Israel in late 1999.

Q. Can West Nile virus cause illness in dogs or cats?
A. There is a published report of West Nile virus isolated from a dog in southern Africa (Botswana) in 1982. There are no published reports regarding cats, but West Nile virus was isolated from a dead cat in the New York area epidemic. A serosurvey of dogs and cats in the epidemic area showed a low infection rate.

Q. Can infected dogs or cats be carriers (i.e., reservoirs) for, and transmit West Nile virus to humans?
A. West Nile virus is transmitted by infectious mosquitoes. There is no documented evidence of person-to-person, animal-to-animal, or animal-to-person transmission of West Nile virus. Veterinarians should take normal infection control precautions when caring for an animal suspected to have this or any viral infection.

Q. How do dogs or cats become infected with West Nile virus?
A. The same way humans become infected, by the bite of infectious mosquitoes. The virus is located in the mosquito's salivary glands. During blood feeding, the virus is injected into the animal. The virus then multiplies and may cause illness. Mosquitoes become infected when they feed on infected birds, which may circulate the virus in their blood for a few days. It is possible that dogs and cats could become infected by eating dead infected animals such as birds, but this is unproven.

Q. Can a dog or cat infected with West Nile virus infect other dogs or cats?
A. No. There is no documented evidence that West Nile virus is transmitted from animal-to-animal.

Q. How long can a dog or cat be infected with West Nile virus ?
A. The answer is not known at this time.

Q. Should a dog or cat infected with West Nile virus be destroyed? What is the treatment for an animal infected with West Nile virus?
A. No. There is no reason to destroy an animal just because it has been infected with West Nile virus. Full recovery from the infection is likely. Treatment would be supportive and consistent with standard veterinary practices for animals infected with a viral agent.

Q. Are duck and other wild game hunters at risk for West Nile virus infection?
A. We do not know. The extent to which West Nile virus may be present in wild game is unknown. Surveillance studies are currently underway in collaboration with the U.S. Geological Survey (USGS) National Wildlife Health Center, Madison, WI, and state and local wildlife biologists and naturalists, to answer this question.

Q. What should wild game hunters do to protect against West Nile virus infection?
A. A hunter should follow the usual precautions when handling wild animals. If you anticipate being exposed to mosquitoes, apply insect repellents to clothing and skin, according to label instructions, to prevent mosquito bites. Wear gloves when handling and cleaning animals to prevent blood exposure to bare hands. Cook meat thoroughly.

Q. Who should wild game hunters contact for information about the risk for West Nile virus infection in specific geographic areas?
A. Hunters should check with their local area department of wildlife and naturalist resources, state epidemiologist at the state health department, or the U.S. Geological Survey (USGS) National Wildlife Health Center, Madison, WI, 608-270-2400 for information on local area risk.

Q. Were the horse deaths reported on Long Island, NY, due to West Nile virus?
A. West Nile virus has been identified in the tissue of several horses that died on Long Island, NY, in October 1999, and specific West Nile antibody has been observed in others. Investigations by the USDA and CDC indicate that West Nile virus was responsible for some of the horse deaths.

Q. How do the horses become infected with West Nile virus?
A. The same way humans become infected, by the bite of infectious mosquitoes while biting to take blood. The virus is located in the mosquito's salivary glands. During the bloodmeal, the virus is injected into the blood system of the horse. The virus then multiplies and may cause illness. The mosquitoes become infected when they feed on infected birds or other animals.

Q. What actually causes the horse's death?
A. Following transmission by an infected mosquito, West Nile virus multiples in the horse's blood system, crosses the blood brain barrier and infects the brain. The virus interferes with normal central nervous system functioning and causes inflammation of the brain.

Q. Can I get infected with West Nile virus by caring for an infected horse?
A. West Nile virus is transmitted by infectious mosquitoes. There is no documented evidence of person-to-person, or animal-to-person transmission of West Nile virus. Normal veterinary infection control precautions should be followed when caring for a horse suspected to have this or any viral infection.

Q. Can a horse infected with West Nile virus infect horses in neighboring stalls?
A. No. There is no documented evidence that West Nile virus is transmitted from horse-to-horse. However, horses with suspected West Nile virus should be isolated from mosquito bites, if at all possible.

Q. My horse is vaccinated against eastern equine encephalitis (EEE), western equine encephalitis (WEE), and Venezuelan equine encephalitis (VEE). Will these vaccines protect my horse against West Nile virus infection?
A. No. EEE, WEE, and VEE belong to another family of viruses for which there is no cross-protection. There is no approved vaccine currently available for West Nile virus.

Q. How long will a horse infected with West Nile virus be infectious?
A. We do not know if an infected horse can be infectious, i.e., cause mosquitoes feeding on it to become infected. However, previously published data suggest that the virus is detectable in the blood for only a few days.

Q. Should a horse infected with West Nile virus be destroyed? What is the treatment for a horse infected with West Nile virus?
A. No. There is no reason to destroy a horse just because it has been infected with West Nile virus. Data suggest that most horses recover from the infection. Treatment would be supportive and consistent with standard veterinary practices for animals infected with a viral agent.

Q. What can I do to reduce my risk of becoming infected with West Nile virus?
A.

  • Stay indoors at dawn, dusk, and in the early evening.
  • Wear long-sleeved shirts and long pants whenever you are outdoors.
  • Apply insect repellent sparingly to exposed skin. An effective repellent will contain 35% DEET (N,N-diethyl-meta-toluamide). DEET in high concentrations (greater than 35%) provides no additional protection.
  • Repellents may irritate the eyes and mouth, so avoid applying repellent to the hands of children.
  • Spray clothing with repellents containing permethrin or DEET, as mosquitoes may bite through thin clothing.
  • Whenever you use an insecticide or insect repellent, be sure to read and follow the manufacturer's DIRECTIONS FOR USE, as printed on the product.
  • Note: Vitamin B and "ultrasonic" devices are NOT effective in preventing mosquito bites.
  • Q. Where can I get more information on mosquito repellents?
    A. Visit the American College of Physicians web site: Mark S. Fradin, MD. Mosquitoes and mosquito repellents: A clinician's guide. Annals of Internal Medicine, June 1 1998. 128:931-940.

    Q. Where can I get more information on horses and West Nile virus?
    A. Visit the USDA web site Animal and Plant Inspection Service (APHIS).

    Q. Where can I get more information on pesticides used to control mosquito populations?
    A. Visit the Environmental Protection Agency (EPA) web site on Pesticides and Mosquito Control.

    Q. Where can I get more information on mosquito-borne viral encephalitis?
    A. Visit the CDC website on Arboviral Encephalitides.

    Source: Centers for Disease Control and Prevention