West Nile Virus Vaccine Challenge Study Q&A

Research and Development representatives from Fort Dodge Animal Health presented results from their challenge study of the West Nile virus (WNV) vaccine on Sept. 18. The information was presented at the World Organisation for Animal Health (Office International des Epizooties--OIE) meeting "Vaccines for OIE list A and Emerging Diseases" in Ames, Iowa. The presentation followed the USDA’s approval late last week to release the abstract detailing the study.

Fort Dodge’s vaccine was released with a conditional license from the USDA in August 2001, and that license was renewed in July of this year. (In order to obtain a conditional license, a vaccine must show purity, safety, and a reasonable expectation of efficacy—-read about the vaccine’s release at http://www.TheHorse.com/ViewArticle.aspx?ID=1109,) Information has been and still is largely unavailable on the specifics of this study due to the fact that the vaccine remains under consideration for full licensure from the USDA.

The WNV vaccine challenge study was completed on normal healthy horses, isolated from natural exposure. Read the abstract at http://www.TheHorse.com/ViewArticle.aspx?ID=3813. Yu-Wei Chang, MS, PhD, of Fort Dodge Animal Health and one of the authors of the study, answered some questions about the study and its results.

The Horse: How were horses experimentally challenged in the study (how was the viremia introduced)? Was it through injection, or through the bite of a mosquito as in the Centers for Disease Control (CDC) and Colorado State University (CSU) transmission studies of a few years ago? (Researchers used virus-infected mosquitoes to administer the disease to horses in experimental studies.)

Chiang: Let me first clarify the term " viremia." Viremia means the presence of viruses in the blood circulation. It is a prerequisite for the induction of neurological disease caused by WNV. In other words, no neurological signs caused by WNV infection would be expected without the occurrence of viremia. Therefore, if viremia is prevented then neurological disease is prevented.

We use needle challenge, not mosquito challenge as done by CDC/CSU. We chose needle challenge hoping to induce more clinical signs than had been reported for mosquito challenge. Also, with needle challenge the scientist has more definite control on the uniformity of challenge dose among the test subjects. However, the outcome of the needle challenge is very similar to mosquito challenge (i.e., the most consistent outcome is the induction of viremia). We believe this virus by its nature may produce viremia in many horses, but only a few infected horses become clinical (show clinical signs of the disease).  Unfortunately the clinical picture for those is very serious.

The Horse: The abstract says that nine of 11 control horses (horses which did not receive the vaccine) developed viremia, and only one of 19 vaccinates had transient viremia. Please explain what transient viremia means.

Chiang: Transient viremia in this study means that the viremia in this vaccinate was detected only once. We collected serum samples twice daily for 14 days then once weekly thereafter until 21 days post-challenge. In control horses, the frequency of detecting viremia ranged from one to seven.

The Horse:You tested these horses with serum neutralization antibody response tests. What does this mean?

Chiang: Serum neutralization antibody response means the immune response induced by vaccination characterized by the presence of antibodies that have the ability to neutralize viruses. Neutralized viruses are those which have lost their ability to cause disease.

The Horse: Is it typical for horses challenged with WNV in research studies to only develop viremia and not exhibit clinical signs or gross pathological signs of WNV in tissue or cerebrospinal fluid, as in this study? Is this typical for what is exhibited in herds when they are exposed to the virus?

Chiang: We think so, yes. We still don't know why some horses develop clinical disease and some don't, when they are all infected by the virus. I understand some people would say that the challenge model we used doesn¹t really reflect what is in the field. However, as I pointed out above, no neurological signs caused by WNV infection would be expected without the occurrence of viremia. Therefore, if we use a challenge model that consistently induces viremia in 80% or more of control animals challenged, and the parameter for the evaluation of the vaccine efficacy is the prevention of viremia, this is good as if we had used a challenge model that would induce clinical disease.

The Horse: In your own words, please describe the overall efficacy of the killed WNV vaccine as reflected by the challenge study.

Chiang: In this study we challenged the horses 12 months after the second vaccination. The vaccine proved to be highly efficacious (94% of preventable fraction) in the vaccinated horses as compared to the unvaccinated controls.

The Horse: What does the company recommend in terms of booster vaccinations, as a reflection of the challenge study?

Chiang: The data from the challenge study has clearly demonstrated the efficacy of the vaccine; thus, as we always recommend: follow the instruction on the label or the recommendation of your veterinarian.

The Horse: What generally happens when a veterinarian reports a horse that was fully vaccinated but developed WNV? Does FDAH follow up or record each instance?

If the vet calls our Professional Services, the case will be followed up and recorded.

The Horse: What is the status of the vaccine's license?

Chiang: USDA renewed our conditional license this July. The data on safety, purity, efficacy, and duration of immunity have all been formally approved by USDA. We are very close to the full licensure, once we tie up some loose ends related to the potency test..





About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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