Live-attenuated recombinant equine herpesvirus type 1 (EHV-1) induces a neutralizing antibody response against West Nile virus (WNV).
Abstract: The immunogenicity in horses of a recombinant equine herpesvirus type 1 (EHV-1) vaccine expressing West Nile virus (WNV) prM and E proteins was studied. To construct the recombinant EHV-1, two-step en passant mutagenesis was employed for manipulation of a bacterial artificial chromosome (BAC) of vaccine strain RacH. Recombinant EHV-1 stably expressed the WNV prM and E proteins as demonstrated by indirect immunofluorescence and Western blotting. In addition, growth properties in vitro of the EHV-1/WNV recombinant were found to not be significantly different from those of the parental virus. To determine if vaccination of horses induces an antibody response, 10 horses were allocated in two groups. Group A consisted of six horses that were vaccinated three times with the recombinant EHV-1/WNV virus in 28- to 31-day intervals. Group B consisted of four horses that were sham-vaccinated using the same regimen. Serum was collected on days 0, 31, 45 and 66. Plaque reduction neutralization test and IgG(T)- and IgGb-specific WNV E antibody-capture ELISAs were used. After a single vaccination (day 31), at least four of the six horses from group A had detectable levels of serum neutralizing antibodies against WNV, and three horses retained SN titers until the end of the study. None of the horses in the control group B sero-converted. On days 31 and 45, five of the six horses in group A had a marked increase of WNV-specific IgG(T), and at least four exhibited modestly elevated WNV-specific IgGb titers. From the results, we concluded that the EHV-1 vectored virus is able to express the WNV structural proteins and that vaccination of horses results in the induction of WNV E-protein-specific IgG(T), IgGb, and neutralizing antibodies.
Publication Date: 2007-01-22 PubMed ID: 17241683DOI: 10.1016/j.virusres.2006.12.009Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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The research was focused on the development and testing of a hybrid vaccine, created from the equine herpesvirus type 1 (EHV-1) carrying the proteins of West Nile virus (WNV). The study confirmed that the vaccine caused an immune response in horses, specifically the production of antibodies that can neutralise West Nile virus.
Development of the Hybrid Vaccine
- The researchers built the hybrid vaccine by integrating the proteins of the West Nile virus into the equine herpesvirus type 1.
- To do this, a method known as two-step en passant mutagenesis was used.
- This method involved manipulating a bacterial artificial chromosome (BAC) of the RacH vaccine strain to generate a recombinant EHV-1.
- The researchers confirmed the stable expression of West Nile virus proteins prM and E in the recombinant EHV-1 via indirect immunofluorescence and Western blotting.
- The modified EHV-1 maintained similar in vitro growth properties to the original virus, confirming the genetic modification didn’t significantly alter the virus’s properties.
Vaccination and Serum Analysis
- 10 horses were divided into two groups for the experiment, with group A receiving three doses of the recombinant EHV-1/WNV vaccine and group B (control group) being sham-vaccinated using the same regimen.
- After a single dose, four out of six vaccinated horses demonstrated detectable levels of serum neutralizing antibodies against WNV. Three of these horses retained the serum neutralizing (SN) titers until the study’s conclusion.
- Meanwhile, none of the horses from the control group demonstrated a similar response.
- The research team also examined other types of antibodies (IgG(T) and IgGb), finding that five out of six vaccinated horses displayed significantly increased WNV-specific IgG(T) on days 31 and 45. Similarly, at least four of the vaccinated horses showed elevated WNV-specific IgGb titers.
Conclusions
- The researchers concluded that the equine herpesvirus type 1 vectored virus can effectively express West Nile virus structural proteins.
- They further established that vaccination of horses with this recombinant vaccine resulted in the production of WNV E-protein-specific IgG(T), IgGb, and neutralizing antibodies.
- These findings suggest that the hybrid vaccine is a promising tool in the battle against West Nile virus in horses.
Cite This Article
APA
Rosas CT, Tischer BK, Perkins GA, Wagner B, Goodman LB, Osterrieder N.
(2007).
Live-attenuated recombinant equine herpesvirus type 1 (EHV-1) induces a neutralizing antibody response against West Nile virus (WNV).
Virus Res, 125(1), 69-78.
https://doi.org/10.1016/j.virusres.2006.12.009 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Antibody Formation
- Cell Line
- Herpesvirus 1, Equid / immunology
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses / immunology
- Neutralization Tests
- Recombinant Proteins
- Vaccines, Attenuated / immunology
- Viral Vaccines / therapeutic use
- West Nile Fever / immunology
- West Nile Fever / veterinary
- West Nile virus / immunology
- West Nile virus / isolation & purification
Grant Funding
- 5 R21 AI061412 / NIAID NIH HHS
Citations
This article has been cited 10 times.- Said A, Elmanzalawy M, Ma G, Damiani AM, Osterrieder N. An equine herpesvirus type 1 (EHV-1) vector expressing Rift Valley fever virus (RVFV) Gn and Gc induces neutralizing antibodies in sheep. Virol J 2017 Aug 14;14(1):154.
- Acharya D, Bai F. An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection. Methods Mol Biol 2016;1435:249-91.
- Brandler S, Tangy F. Vaccines in development against West Nile virus. Viruses 2013 Sep 30;5(10):2384-409.
- Iyer AV, Kousoulas KG. A review of vaccine approaches for West Nile virus. Int J Environ Res Public Health 2013 Sep 10;10(9):4200-23.
- Ma G, Eschbaumer M, Said A, Hoffmann B, Beer M, Osterrieder N. An equine herpesvirus type 1 (EHV-1) expressing VP2 and VP5 of serotype 8 bluetongue virus (BTV-8) induces protection in a murine infection model. PLoS One 2012;7(4):e34425.
- Tischer BK, Kaufer BB. Viral bacterial artificial chromosomes: generation, mutagenesis, and removal of mini-F sequences. J Biomed Biotechnol 2012;2012:472537.
- Spiesschaert B, McFadden G, Hermans K, Nauwynck H, Van de Walle GR. The current status and future directions of myxoma virus, a master in immune evasion. Vet Res 2011 Jun 9;42(1):76.
- Warden C, Tang Q, Zhu H. Herpesvirus BACs: past, present, and future. J Biomed Biotechnol 2011;2011:124595.
- Brun A, Albina E, Barret T, Chapman DA, Czub M, Dixon LK, Keil GM, Klonjkowski B, Le Potier MF, Libeau G, Ortego J, Richardson J, Takamatsu HH. Antigen delivery systems for veterinary vaccine development. Viral-vector based delivery systems. Vaccine 2008 Dec 2;26(51):6508-28.
- Rosas C, Van de Walle GR, Metzger SM, Hoelzer K, Dubovi EJ, Kim SG, Parrish CR, Osterrieder N. Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza. Vaccine 2008 May 2;26(19):2335-43.
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