Safety of an attenuated West Nile virus vaccine, live Flavivirus chimera in horses.
Abstract: West Nile virus (WNV) infection is endemic and able to cause disease in naive hosts. It is necessary therefore to evaluate the safety of new vaccines. Objective: To establish: 1) the safety of a modified live Flavivirus/West Nile virus (WN-FV) chimera by administration of an overdose and testing for shed of vaccine virus and spread to uninoculated sentinel horses; 2) that this vaccine did not become pathogenic once passaged in horses; and 3) vaccine safety under field conditions. Methods: There were 3 protocols: 1) In the overdose/shed and spread study, horses were vaccinated with a 100x immunogenicity overdose of WN-FV chimera vaccine and housed with sentinel horses. 2) A reversion to virulence study, where horses were vaccinated with a 20x immunogenicity overdose of WN-FV chimera vaccine. Horses in both studies were evaluated for abnormal health conditions and samples obtained to detect virus, seroconversion and dissemination into tissues. 3) In a field safety test 919 healthy horses of various ages, breeds and sex were used. Results: Vaccination did not result in site or systemic reactions in either experimental or field-injected horses. There was no shed of vaccine virus, no detection of vaccine virus into tissue and no reversion to virulence with passage. Conclusions: WN-FV chimera vaccine is safe to use in horses with no evidence of ill effects from very high doses of vaccine. There was no evidence of reversion to virulence. In addition, administration of this vaccine to several hundred horses that may have been previously exposed to WNV or WNV vaccine resulted in no untoward reactions. Conclusions: These studies establish that this live attenuated Flavivirus chimera is safe to use for immunoprophylaxis against WNV disease in horses.
Publication Date: 2007-12-11 PubMed ID: 18065304DOI: 10.2746/042516407X214473Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article presents a study on the safety of a modified live West Nile virus vaccine for use in horses, demonstrating that the vaccine does not cause ill effects even when administered in very high doses.
Objective and Methodology
- The objective of the study was threefold: to assess the safety of the vaccine by administering an overdose and testing for shedding of the vaccine virus and its spread to non-vaccinated horses; to verify that the vaccine did not become pathogenic when passaged in horses; and to evaluate the vaccine’s safety under field conditions.
- Three protocols were followed in this research. The first part focused on an overdose study wherein horses were given a hundred times the immunogenicity overdose of the West Nile – Flavivirus (WN-FV) chimera vaccine and then kept with non-vaccinated sentinel horses. The second part was a ‘reversion to virulence’ study where horses were given a twenty times the immunogenicity overdose of the WN-FV chimera vaccine. All the horses were monitored for any unusual health conditions and their samples were collected for virus detection, seroconversion, and penetration into tissues.
- A field safety test was conducted involving 919 healthy horses of varying ages, breeds, and genders where the vaccine’s safety was evaluated in the real world.
Results of the Study
- The results of this research proved that the WN-FV chimera vaccine did not cause any reactions at the site of vaccination or systemic reactions in horses. The vaccine did not shed or enter tissues and did not revert to virulence despite being passaged.
- Neither the overdose nor the reversion studies indicated any adverse health effects in the horses. Moreover, the field safety test revealed that the vaccine did not cause any adverse reactions in a diverse population of horses, even ones that might have previously been exposed to West Nile virus or its vaccine.
Conclusion
- Based on the research findings, the WN-FV chimera vaccine is deemed safe for use in horses as it doesn’t cause any ill effects even when administered in excessively high doses. There was no evidence of the vaccine becoming virulent again.
- The vaccine also proved safe during the field trials, including for horses possibly exposed to the West Nile virus or its vaccine in the past. Therefore, the paper concludes that this live attenuated Flavivirus chimera is safe for use as a protective mechanism against West Nile disease in horses.
Cite This Article
APA
Long MT, Gibbs EP, Mellencamp MW, Zhang S, Barnett DC, Seino KK, Beachboard SE, Humphrey PP.
(2007).
Safety of an attenuated West Nile virus vaccine, live Flavivirus chimera in horses.
Equine Vet J, 39(6), 486-490.
https://doi.org/10.2746/042516407X214473 Publication
Researcher Affiliations
- College of Veterinary Medicine, University of Florida, 2015 SW 16th Ave., Gainesville, Florida, USA.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Chimera
- Dose-Response Relationship, Immunologic
- Feces / virology
- Female
- Horse Diseases / epidemiology
- Horse Diseases / prevention & control
- Horse Diseases / transmission
- Horses
- Male
- Safety
- Time Factors
- Vaccines, Attenuated / administration & dosage
- Vaccines, Attenuated / adverse effects
- Vaccines, Attenuated / immunology
- Virulence
- West Nile Fever / epidemiology
- West Nile Fever / prevention & control
- West Nile Fever / transmission
- West Nile Fever / veterinary
- West Nile Virus Vaccines / administration & dosage
- West Nile Virus Vaccines / adverse effects
- West Nile Virus Vaccines / immunology
- West Nile virus / immunology
- West Nile virus / pathogenicity
Citations
This article has been cited 5 times.- Gothe LMR, Ganzenberg S, Ziegler U, Obiegala A, Lohmann KL, Sieg M, Vahlenkamp TW, Groschup MH, Hörügel U, Pfeffer M. Horses as Sentinels for the Circulation of Flaviviruses in Eastern-Central Germany.. Viruses 2023 Apr 30;15(5).
- Arfuso F, Giudice E, Di Pietro S, Piccione G, Giannetto C. Modulation of Serum Protein Electrophoretic Pattern and Leukocyte Population in Horses Vaccinated against West Nile Virus.. Animals (Basel) 2021 Feb 11;11(2).
- Byas AD, Ebel GD. Comparative Pathology of West Nile Virus in Humans and Non-Human Animals.. Pathogens 2020 Jan 7;9(1).
- Monath TP, Seligman SJ, Robertson JS, Guy B, Hayes EB, Condit RC, Excler JL, Mac LM, Carbery B, Chen RT. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.. Vaccine 2015 Jan 1;33(1):62-72.
- Bourgeois MA, Denslow ND, Seino KS, Barber DS, Long MT. Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus.. PLoS One 2011;6(10):e24371.
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