Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.
Abstract: African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV.
Copyright © 2017. Published by Elsevier Ltd.
Publication Date: 2017-06-29 PubMed ID: 28625521PubMed Central: PMC5518735DOI: 10.1016/j.vaccine.2017.06.023Google Scholar: Lookup
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- Journal Article
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Summary
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The research involves the testing of a new generation of vaccines for the African horse sickness virus (AHSV). These vaccines called Entry Competent Replication-Abortive (ECRA) strains were tested on ponies and showed promising results in protecting them against AHSV.
Introduction to AHSV
- African horse sickness virus (AHSV) is a member of the Reoviridae family, categorized as an orbivirus.
- There have been nine documented serotypes (variations) of the virus.
- Culicoides spp., a type of biting midge, act as vectors transmitting AHSV to equids, a family of animals that includes horses.
- The virus causes high mortality rates in horses, resulting in significant economic losses.
The Vaccine Development Process
- Previously, researches developed a system called reverse genetics (RG) to create Entry Competent Replication-Abortive (ECRA) virus strains pertaining to all nine serotypes of AHSV. They verified the efficacy of these strains provisionally in IFNAR-knockout mice.
- The ECRA strains are essentially designed to initiate infection but stop short of replicating completely, this assists in stimulating an immune response without causing disease symptoms.
- In this study, they moved further by testing these virus strains in ponies (natural host for AHSV) to evaluate their protective capabilities.
Experiment and results
- The researchers tested two types of vaccines: a single serotype vaccine referred to as ECRA.A4, and a multivalent cocktail ECRA.A1/4/6/8 containing four serotypes.
- The ponies were vaccinated and then exposed to a virulent strain of AHSV4 (a subtype of the virus).
- While unvaccinated control animals fell sick, all vaccinated ponies were protected and did not present any severe symptoms associated with African horse sickness (AHS).
- The multivalent cocktail also stimulated an immune response which resulted in the production of neutralizing antibodies against all serotypes present in the cocktail.
- An additional positive result was a foal born during the trial was healthy, and there were no traces of the virus in its blood (no viremia).
Implications of the Study
- The positive outcomes of this study confirm that these ECRA strains could be considered as effective vaccines against AHSV.
- The successful production of neutralizing antibodies against multiple serotypes in the vaccinated ponies further supports multi-serotype ECRA-based vaccine utility to combat different strain variations of AHSV.
- The absence of viremia in the newborn foal demonstrates that these strains could be safe to use in pregnant mares, reducing the risk of in utero transmission.
Cite This Article
APA
Lulla V, Losada A, Lecollinet S, Kerviel A, Lilin T, Sailleau C, Beck C, Zientara S, Roy P.
(2017).
Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.
Vaccine, 35(33), 4262-4269.
https://doi.org/10.1016/j.vaccine.2017.06.023 Publication
Researcher Affiliations
- Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Université Paris-Est ANSES Alfort, UMR 1161 Virologie ANSES, INRA, ENVA, Maisons-Alfort, France.
- Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom. Electronic address: polly.roy@lshtm.ac.uk.
MeSH Terms
- African Horse Sickness / immunology
- African Horse Sickness / pathology
- African Horse Sickness / prevention & control
- African Horse Sickness Virus / immunology
- African Horse Sickness Virus / physiology
- Animals
- Antibodies, Neutralizing / blood
- Antibodies, Viral / blood
- Horses
- Reverse Genetics
- Vaccines, Attenuated / administration & dosage
- Vaccines, Attenuated / genetics
- Vaccines, Attenuated / immunology
- Vaccines, Synthetic / administration & dosage
- Vaccines, Synthetic / genetics
- Vaccines, Synthetic / immunology
- Viral Vaccines / administration & dosage
- Viral Vaccines / genetics
- Viral Vaccines / immunology
- Virus Replication
Grant Funding
- BB/K015168/1 / Biotechnology and Biological Sciences Research Council
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Citations
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