VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA.

F. Feenstra, M.A. Maris-Veldhuis, F.J. Daus, M.G.J. Tacken, R.J.M. Moormann, H.G.P. van Gennip, P.A. van Rijn

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Abstract

Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome segment 2 encoding the VP2 protein. Currently, inactivated and live-attenuated Bluetongue vaccines are available for a limited number of serotypes, but each of these have their specific disadvantages, including the inability to differentiate infected from vaccinated animals (DIVA). BTV non-structural proteins NS3 and NS3a are not essential for virus replication in vitro, but are important for cytopathogenic effect in mammalian cells and for virus release from insect cells in vitro. Recently, we have shown that virulent BTV8 without NS3/NS3a is non-virulent and viremia in sheep is strongly reduced, whereas local in vivo replication leads to seroconversion. Live-attenuated BTV6 without NS3/NS3a expression protected sheep against BTV challenge. Altogether, NS3/NS3a knockout BTV6 is a promising vaccine candidate and has been named Disabled Infectious Single Animal (DISA) vaccine. Here, we show serotype-specific protection in sheep by DISA vaccine in which only genome segment 2 of serotype 8 was exchanged. Similarly, DISA vaccines against other serotypes could be developed, by exchange of only segment 2, and could therefore safely be combined in multi-serotype cocktail vaccines with respect to reassortment between vaccine viruses. Additionally, NS3 antibody responses are raised after natural BTV infection and NS3-based ELISAs are therefore appropriate tools for DIVA testing accompanying the DISA vaccine. To enable DIVA, we developed an experimental NS3 ELISA. Indeed, vaccinated sheep remained negative for NS3 antibodies, whereas seroconversion for NS3 antibodies was associated with viremia after heterologous BTV challenge.
Original languageEnglish
Pages (from-to)7108-7114
JournalVaccine
Volume32
Issue number52
DOIs
Publication statusPublished - 2014

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Bluetongue virus
serotypes
Vaccines
vaccines
Sheep
Bluetongue
animals
Ceratopogonidae
sheep
Viremia
bluetongue
viremia
seroconversion
antibodies
Enzyme-Linked Immunosorbent Assay
Genome
Cross Protection
Viral Structural Proteins
Virus Release
Disease Vectors

Cite this

Feenstra, F., Maris-Veldhuis, M. A., Daus, F. J., Tacken, M. G. J., Moormann, R. J. M., van Gennip, H. G. P., & van Rijn, P. A. (2014). VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA. Vaccine, 32(52), 7108-7114. https://doi.org/10.1016/j.vaccine.2014.10.033
Feenstra, F. ; Maris-Veldhuis, M.A. ; Daus, F.J. ; Tacken, M.G.J. ; Moormann, R.J.M. ; van Gennip, H.G.P. ; van Rijn, P.A. / VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA. In: Vaccine. 2014 ; Vol. 32, No. 52. pp. 7108-7114.
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abstract = "Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome segment 2 encoding the VP2 protein. Currently, inactivated and live-attenuated Bluetongue vaccines are available for a limited number of serotypes, but each of these have their specific disadvantages, including the inability to differentiate infected from vaccinated animals (DIVA). BTV non-structural proteins NS3 and NS3a are not essential for virus replication in vitro, but are important for cytopathogenic effect in mammalian cells and for virus release from insect cells in vitro. Recently, we have shown that virulent BTV8 without NS3/NS3a is non-virulent and viremia in sheep is strongly reduced, whereas local in vivo replication leads to seroconversion. Live-attenuated BTV6 without NS3/NS3a expression protected sheep against BTV challenge. Altogether, NS3/NS3a knockout BTV6 is a promising vaccine candidate and has been named Disabled Infectious Single Animal (DISA) vaccine. Here, we show serotype-specific protection in sheep by DISA vaccine in which only genome segment 2 of serotype 8 was exchanged. Similarly, DISA vaccines against other serotypes could be developed, by exchange of only segment 2, and could therefore safely be combined in multi-serotype cocktail vaccines with respect to reassortment between vaccine viruses. Additionally, NS3 antibody responses are raised after natural BTV infection and NS3-based ELISAs are therefore appropriate tools for DIVA testing accompanying the DISA vaccine. To enable DIVA, we developed an experimental NS3 ELISA. Indeed, vaccinated sheep remained negative for NS3 antibodies, whereas seroconversion for NS3 antibodies was associated with viremia after heterologous BTV challenge.",
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VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA. / Feenstra, F.; Maris-Veldhuis, M.A.; Daus, F.J.; Tacken, M.G.J.; Moormann, R.J.M.; van Gennip, H.G.P.; van Rijn, P.A.

In: Vaccine, Vol. 32, No. 52, 2014, p. 7108-7114.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA.

AU - Feenstra, F.

AU - Maris-Veldhuis, M.A.

AU - Daus, F.J.

AU - Tacken, M.G.J.

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AU - van Rijn, P.A.

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AB - Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome segment 2 encoding the VP2 protein. Currently, inactivated and live-attenuated Bluetongue vaccines are available for a limited number of serotypes, but each of these have their specific disadvantages, including the inability to differentiate infected from vaccinated animals (DIVA). BTV non-structural proteins NS3 and NS3a are not essential for virus replication in vitro, but are important for cytopathogenic effect in mammalian cells and for virus release from insect cells in vitro. Recently, we have shown that virulent BTV8 without NS3/NS3a is non-virulent and viremia in sheep is strongly reduced, whereas local in vivo replication leads to seroconversion. Live-attenuated BTV6 without NS3/NS3a expression protected sheep against BTV challenge. Altogether, NS3/NS3a knockout BTV6 is a promising vaccine candidate and has been named Disabled Infectious Single Animal (DISA) vaccine. Here, we show serotype-specific protection in sheep by DISA vaccine in which only genome segment 2 of serotype 8 was exchanged. Similarly, DISA vaccines against other serotypes could be developed, by exchange of only segment 2, and could therefore safely be combined in multi-serotype cocktail vaccines with respect to reassortment between vaccine viruses. Additionally, NS3 antibody responses are raised after natural BTV infection and NS3-based ELISAs are therefore appropriate tools for DIVA testing accompanying the DISA vaccine. To enable DIVA, we developed an experimental NS3 ELISA. Indeed, vaccinated sheep remained negative for NS3 antibodies, whereas seroconversion for NS3 antibodies was associated with viremia after heterologous BTV challenge.

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