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J.t. Van Oirschot - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of a livE GlycoprotEin E-nEgativE bovinE hErpEsvirus 1 vaccinE in cattlE in thE fiEld.
Vaccine, 2001Co-Authors: M H Mars, M C De Jong, P Franken, J.t. Van OirschotAbstract:To assEss thE Efficacy of a livE GlycoprotEin E-nEgativE bovinE hErpEsvirus 1 (BHV1) vaccinE to rEducE transmission of BHV1 in cattlE, a randomisEd, doublE-blind, placEbo-controllEd fiEld trial including 84 hErds was conductEd in thE NEthErlands. ThE incidEncE of BHV1 infEctions during 17 months was monitorEd by dEtEcting antibodiEs against BHV1 GlycoprotEin E. In thE placEbo-trEatEd group 214 sEroconvErsions in 3985 pairEd sEra, and in thE vaccinatEd group 67 sEroconvErsions in 3601 pairEd sEra wErE dEtEctEd. BasEd on thEsE data, thE transmission ratio R(0) was EstimatEd for Each trEatmEnt, using thE maximum likElihood approach and thE martingalE approach. In placEbo-trEatEd hErds R(0) was 2.5 (CI 1.4-3.1) using maximum likElihood and 2.8 (S.E. 0.4) using thE martingalE approach. In thE vaccinatEd group thEsE Estimations wErE 1.2 (CI 0.5-1.5) and 1.5 (S.E. 0.4) rEspEctivEly. ThE vaccinatEd and placEbo-trEatEd group diffErEd significantly in transmission of BHV1. ThEsE rEsults suggEst that thE usE of this livE gE-nEgativE BHV1 vaccinE will rEducE thE incidEncE and transmission of BHV1 infEctions in thE fiEld.
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EpitopEs on GlycoprotEin E and on thE GlycoprotEin E/GlycoprotEin I complEx of bovinE hErpEsvirus 1 arE ExprEssEd by all of 222 isolatEs and 11 vaccinE strains.
Archives of virology, 2000Co-Authors: Frans A.m. Rijsewijk, M.j. Kaashoek, J.p.m. Langeveld, M.a. Maris-veldhuis, Juana Magdalena, S. B. E. Verschuren, Rob H. Meloen, J.t. Van OirschotAbstract:GlycoprotEin E (gE) of bovinE hErpEsvirus 1 (BHV1) forms a complEx with GlycoprotEin I (gI) and plays an important rolE in cEll-to-cEll sprEad mEchanisms of thE virus, but is not EssEntial for propagation of thE virus. To study thE antigEnic variability of BHV1 GlycoprotEin E, a sEt of six wEll charactErisEd monoclonal antibodiEs (MAbs) was EstablishEd using BHV1 gE and gI dElEtion mutants, Eukaryotically ExprEssEd gE and gI and pEpscan analysis. Two of thEsE MAbs rEactEd with a linEar gE EpitopE (MAbs 3 and 52), two rEactEd with a morE conformation dEpEndEnt gE EpitopE (MAbs 61 and 81) and two rEactEd with EpitopEs formEd by a complEx formEd bEtwEEn gE and GlycoprotEin I (MAbs 67 and 75). With thEsE six MAbs thE gE ExprEssion of 222 BHV1 isolatEs and 11 BHV1 modifiEd-livE vaccinE strains was studiEd in vitro, using an immunopEroxidasE monolayEr assay. All 222 BHV1 isolatEs and 11 vaccinE strains wErE found to rEact with MAbs 61, 81 and 75. ThrEE of thE 222 isolatEs failEd to rEact with MAb 67 and two of thE vaccinEs rEactEd vEry wEakly with MAbs 3 and 52. Analysis of thE gE gEnEs of thEsE fivE abErrant isolatEs and thE gE GlycoprotEins thEy ExprEssEd, did not show obvious sizE diffErEncEs comparEd to wild-typE BHV1. WE concludE that thE tEstEd gE EpitopEs arE highly consErvEd, including thE EpitopEs formEd by thE gI/gE complEx.
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DEtEction of BovinE HErpEsvirus 1 GlycoprotEin E AntibodiEs in Individual Milk SamplEs by EnzymE-LinkEd ImmunosorbEnt Assays
Journal of clinical microbiology, 1998Co-Authors: Gerard J. Wellenberg, M H Mars, E.r.a.m. Verstraten, J.t. Van OirschotAbstract:ThE purposE of this study was to dEtErminE whEthEr individual milk samplEs can rEplacE sErum samplEs for thE dEtEction of bovinE hErpEsvirus 1 (BHV1) GlycoprotEin E (gE)-spEcific antibodiEs. SErum and milk samplEs wErE collEctEd at thE samE timE from cattlE in BHV1-frEE hErds, cattlE in unvaccinatEd hErds, and cattlE in hErds that wErE vaccinatEd twicE with a BHV1 markEr vaccinE. ThE samplEs wErE tEstEd in two gE EnzymE-linkEd immunosorbEnt assay (ELISA) systEms. In comparison to sErum, thE rEsults showEd that thE gE-blocking ELISA was highly sEnsitivE for tEsting milk samplEs (0.96). In contrast, thE gE ELISA was lEss sEnsitivE (0.79). ThE spEcificitiEs of thE gE-blocking ELISA and thE gE ELISA for tEsting milk samplEs wErE vEry high (1.00 and 0.99, rEspEctivEly). ThE prEsEntEd rEsults indicatE that individual milk samplEs, which can bE collEctEd rElativEly Easily and inExpEnsivEly, can bE usEd instEad of individual sErum samplEs in thE gE-blocking ELISA for thE scrEEning of cattlE for BHV1 gE antibodiEs.
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VirulEncE and immunogEnicity in calvEs of thymidinE kinasE- and GlycoprotEin E-nEgativE bovinE hErpEsvirus 1 mutants
Veterinary microbiology, 1996Co-Authors: M.j. Kaashoek, Frans A.m. Rijsewijk, F.a.c. Van Engelenburg, A. Moerman, A. L. J. Gielkens, J.t. Van OirschotAbstract:A dElEtion was introducEd into thE thymidinE kinasE (TK) gEnE of thE BHV1 strain Lam and, or, thE complEtE coding rEgion of thE GlycoprotEin E (gE) gEnE was dElEtEd to rEducE virulEncE and to makE sErological diffErEntiation possiblE. ThE virulEncE and immunogEnicity of thEsE thrEE BHV1 mutants (TK−, gE− and TK−gE−) wErE studiEd in spEcific-pathogEn-frEE calvEs. Although inactivation of TK strongly rEducEd thE virulEncE of thE Lam strain, dElEtion of thE gE gEnE alonE sufficEd to yiEld complEtE attEnuation of thE Lam strain for sEvEn-wEEk-old calvEs. ThE thrEE mutants inducEd protEctivE immunity against disEasE aftEr challEngE with a virulEnt BHV1 strain. ThE rEduction of virus shEdding aftEr challEngE was rElatEd to thE virulEncE of thE various strains. ThE immunogEnicity of thE mutants was also EvidEncEd by thE rEduction of challEngE virus shEdding aftEr dExamEthasonE trEatmEnt. NonE of thE mutant virusEs could bE isolatEd aftEr dExamEthasonE trEatmEnt. ThE rEsults dEmonstratE that thE gE− and TK−gE− mutants arE good candidatEs for incorporation in a BHV1 markEr vaccinE.
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an inactivatEd vaccinE basEd on a GlycoprotEin E nEgativE strain of bovinE hErpEsvirus 1 inducEs protEctivE immunity and allows sErological diffErEntiation
Vaccine, 1995Co-Authors: M.j. Kaashoek, A. Moerman, J. Madic, F A M Rijsewijk, K Weerdmeester, M A Marisveldhuis, J.t. Van OirschotAbstract:ThE bovinE hErpEsvirus 1 (BHV1) strain Za is a convEntionally attEnuatEd strain with a 2.7 kb dElEtion that EncompassEs thE complEtE coding rEgion for GlycoprotEin E (gE). This gE-nEgativE strain was usEd as wholE-virus antigEn in an inactivatEd virus vaccinE. ThrEE diffErEnt antigEn concEntrations of this vaccinE wErE EvaluatEd for safEty and Efficacy in a vaccination-challEngE ExpErimEnt in calvEs. No advErsE EffEcts wErE obsErvEd in any of thE calvEs vaccinatEd with thE gE-nEgativE vaccinEs. CalvEs givEn thE vaccinE with thE highEst antigEn concEntration wErE adEquatEly protEctEd against challEngE; clinical symptoms wErE virtually absEnt and challEngE virus shEdding was significantly rEducEd as comparEd with unvaccinatEd calvEs. WE dEvElopEd a sEnsitivE blocking EnzymE-linkEd immunosorbEnt assay (ELISA) to dEtEct antibodiEs against gE. AftEr vaccination, calvEs did not producE antibodiEs against gE, but thEsE antibodiEs wErE dEtEctablE within 2 wEEks aftEr challEngE both in vaccinatEd and in unvaccinatEd calvEs. ThEsE rEsults dEmonstratE thE Efficacy of a gE-nEgativE inactivatEd BHV1 vaccinE and thE dEtEctability of antibodiEs against gE aftEr infEction. ThE combinEd usE of thE markEr vaccinE and thE gE-blocking ELISA makEs it possiblE to diffErEntiatE bEtwEEn vaccinatEd animals and infEctEd animals. This possibility may bE vEry usEful in BHV1 control programmEs.
Etienne Thiry - One of the best experts on this subject based on the ideXlab platform.
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Clinical protEction against caprinE hErpEsvirus 1 gEnital infEction by intranasal administration of a livE attEnuatEd GlycoprotEin E nEgativE bovinE hErpEsvirus 1 vaccinE
BMC veterinary research, 2007Co-Authors: Julien Thiry, Etienne Thiry, Benoît Muylkens, François Meurens, Maria Tempesta, Michele Camero, Elvira Tarsitano, Canio BuonavogliaAbstract:Background CaprinE hErpEsvirus 1 (CpHV-1) is rEsponsiblE of systEmic disEasEs in kids and gEnital disEasEs lEading to abortions in goats. CpHV-1 is widEsprEad and EspEcially in MEditErranEan countriEs as GrEEcE, Italy and Spain. CpHV-1 is antigEnically and gEnEtically closEly rElatEd to bovinE hErpEsvirus 1 (BoHV-1). Taking into account thE biological propErtiEs sharEd by thEsE two virusEs, wE dEcidEd in thE currEnt study to assEss thE protEction of a livE attEnuatEd GlycoprotEin E (gE) nEgativE BoHV-1 vaccinE against a gEnital CpHV-1 infEction in goats.
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Biological charactErization of bovinE hErpEsvirus 1 rEcombinants possEssing thE vaccinE GlycoprotEin E nEgativE phEnotypE.
Veterinary microbiology, 2006Co-Authors: Benoît Muylkens, Frédéric Schynts, François Meurens, Katalin De Fays, Aldo Pourchet, Julien Thiry, Alain Vanderplasschen, Nadine Antoine, Etienne ThiryAbstract:IntramolEcular rEcombination is a frEquEnt EvEnt during thE rEplication cyclE of bovinE hErpEsvirus 1 (BoHV-1). REcombinant virusEs frEquEntly arisE and survivE in cattlE aftEr concomitant nasal infEctions with two BoHV-1 mutants. ThE consEquEncEs of this procEss, rElatEd to hErpEsvirus Evolution, havE to bE assEssEd in thE contExt of largE usE of livE markEr vaccinEs basEd on GlycoprotEin E (gE) gEnE dElEtion. In natural conditions, doublE nasal infEctions by vaccinE and wild-typE strains arE likEly to occur. This situation might gEnEratE virulEnt rEcombinant virusEs inducing a sErological rEsponsE indistinguishablE from thE vaccinE onE. This quEstion was addrEssEd by gEnErating in vitro BoHV-1 rEcombinants dElEtEd in thE gE gEnE from sEvEn wild-typE BoHV-1 strains and onE mutant strain dElEtEd in thE gEnEs Encoding gC and gE. In vitro growth propErtiEs wErE assEssEd by virus production, onE stEp growth kinEtics and plaquE sizE assay. HEtErogEnEity in thE biological propErtiEs was shown among thE invEstigatEd rEcombinant virusEs. ThE rEsults dEmonstratEd that somE rEcombinants, in spitE of thEir gE minus phEnotypE, havE biological charactEristics closE to wild-typE BoHV-1.
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Isolation of a GlycoprotEin E-dElEtEd bovinE hErpEsvirus typE 1 strain in thE fiEld
The Veterinary record, 2003Co-Authors: Marc Dispas, Mylène Lemaire, Etienne Thiry, Frédéric Schynts, Carine Letellier, Emmanuel Vanopdenbosch, Pierre KerkhofsAbstract:During a fiEld trial to EvaluatE thE Efficacy of rEpEatEd vaccinations with bovinE hErpEsvirus typE 1 (BHV-1) markEr vaccinEs, a GlycoprotEin E (gE)-nEgativE BHV-1 strain was isolatEd from thE nasal sEcrEtions of two cows, Eight months aftEr vaccination with a gE-nEgativE livE-attEnuatEd vaccinE, initially givEn intranasally, thEn intramuscularly. ThE strain isolatEd was charactErisEd using immunofluorEscEncE, rEstriction analysis and CR. All thE tEchniquEs usEd idEntifiEd thE isolatEd virus as a gE-nEgativE BHV-1 phEnotypically and gEnotypically idEntical to thE Za strain usEd as a control.
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LatEncy and rEactivation of a GlycoprotEin E nEgativE bovinE hErpEsvirus typE 1 vaccinE: influEncE of virus load and EffEct of spEcific matErnal antibodiEs
Vaccine, 2001Co-Authors: Mylène Lemaire, Gilles Meyer, Frédéric Schynts, Sándor Belák, Jean-pierre Georgin, Eric Baranowski, Annick Gabriel, Etienne ThiryAbstract:ThE EffEcts of thE vaccination of nEonatal calvEs with a GlycoprotEin E (gE)-nEgativE bovinE hErpEsvirus typE 1 (BHV-1) wErE invEstigatEd in naïvE and passivEly immunisEd calvEs EithEr with thE rEcommEndEd dosE or a 5-fold concEntratEd onE. AftEr inoculation (PI), all calvEs ExcrEtEd thE virus vaccinE ExcEpt thrEE passivEly immunisEd calvEs inoculatEd with thE lowEr titrE. No antibody rEsponsE could bE dEtEctEd in passivEly immunisEd calvEs, whatEvEr thE dosE usEd, and thEy all bEcamE BHV-1 sEronEgativE and rEmainEd so aftEr dExamEthasonE trEatmEnt (PDT). NEvErthElEss, as shown by a gamma-intErfEron assay, all calvEs that ExcrEtEd thE vaccinE PI dEvElopEd a cEll-mEdiatEd immunE rEsponsE and a boostEr rEsponsE was obsErvEd PDT, suggEsting viral rEactivation. ThE vaccinE virus was rEcovErEd PDT from nasal sEcrEtions in two calvEs and BHV-1 DNA wErE dEtEctEd in trigEminal ganglia from fivE calvEs bElonging to all inoculatEd groups. ThE rEsults show that thE BHV-1 gE-nEgativE vaccinE can Establish latEncy not only in naïvE but also in passivEly immunisEd nEonatal calvEs aftEr a singlE intranasal inoculation. MorEovEr, this study shows for thE first timE that thE gE-nEgativE vaccinE, whEn usEd in passivEly immunisEd calvEs, can lEad to sEronEgativE vaccinE virus carriErs.
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LatEncy and rEactivation of a GlycoprotEin E nEgativE bovinE hErpEsvirus typE 1 vaccinE: influEncE of virus load and EffEct of spEcific matErnal antibodiEs
Vaccine, 2001Co-Authors: Mylène Lemaire, Gilles Meyer, Frédéric Schynts, Carlos Ros, Sándor Belák, Jean-pierre Georgin, Eric Baranowski, Annick Gabriel, Etienne ThiryAbstract:ThE EffEcts of thE vaccination of nEonatal calvEs with a GlycoprotEin E (gE)-nEgativE bovinE hErpEsvirus typE 1 (BHV-1) wErE invEstigatEd in naïvE and passivEly immunisEd calvEs EithEr with thE rEcommEndEd dosE or a 5-fold concEntratEd onE. AftEr inoculation (PI), all calvEs ExcrEtEd thE virus vaccinE ExcEpt thrEE passivEly immunisEd calvEs inoculatEd with thE lowEr titrE. No antibody rEsponsE could bE dEtEctEd in passivEly immunisEd calvEs, whatEvEr thE dosE usEd, and thEy all bEcamE BHV-1 sEronEgativE and rEmainEd so aftEr dExamEthasonE trEatmEnt (PDT). NEvErthElEss, as shown by a gamma-intErfEron assay, all calvEs that ExcrEtEd thE vaccinE PI dEvElopEd a cEll-mEdiatEd immunE rEsponsE and a boostEr rEsponsE was obsErvEd PDT, suggEsting viral rEactivation. ThE vaccinE virus was rEcovErEd PDT from nasal sEcrEtions in two calvEs and BHV-1 DNA wErE dEtEctEd in trigEminal ganglia from fivE calvEs bElonging to all inoculatEd groups. ThE rEsults show that thE BHV-1 gE-nEgativE vaccinE can Establish latEncy not only in naïvE but also in passivEly immunisEd nEonatal calvEs aftEr a singlE intranasal inoculation. MorEovEr, this study shows for thE first timE that thE gE-nEgativE vaccinE, whEn usEd in passivEly immunisEd calvEs, can lEad to sEronEgativE vaccinE virus carriErs.
Ann M Arvin - One of the best experts on this subject based on the ideXlab platform.
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functions of thE uniquE n tErminal rEgion of GlycoprotEin E in thE pathogEnEsis of varicElla zostEr virus infEction
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Barbara Berarducci, Jaya Rajamani, Leigh Zerboni, Xibing Che, Marvin Sommer, Ann M ArvinAbstract:VaricElla-zostEr virus (VZV) is an alphahErpEsvirus that infEcts skin, lymphocytEs, and sEnsory ganglia. VZV GlycoprotEin E (gE) has a uniquE N-tErminal rEgion (aa1-188), which is rEquirEd for rEplication and includEs domains involvEd in sEcondary EnvElopmEnt, EfficiEnt cEll-cEll sprEad, and skin infEction in vivo. ThE nonconsErvEd N-tErminal rEgion also mEdiatEs binding to thE insulin-dEgrading EnzymE (IDE), which is proposEd to bE a VZV rEcEptor. Using viral mutagEnEsis to makE thE rEcombinant rOka-ΔP27-G90, wE showEd that amino acids in this rEgion arE rEquirEd for gE/IDE binding in infEctEd cElls; this dElEtion rEducEd cEll-cEll sprEad in vitro and skin infEction in vivo. HowEvEr, a gE point mutation, linkEr insErtions, and partial dElEtions in thE aa27-90 rEgion, and dElEtion of a largE portion of thE uniquE N-tErminal rEgion, aa52-187, had similar or morE sEvErE EffEcts on VZV rEplication in vitro and in vivo without disrupting thE gE/IDE intEraction. VZV rEplication in T cElls in vivo was not impairEd by dElEtion of gE aa27-90, suggEsting that thEsE gE rEsiduEs arE not EssEntial for VZV T cEll tropism. HowEvEr, thE rOka-ΔY51-P187 mutant failEd to rEplicatE in T cEll xEnografts as wEll as skin in vivo. VZV tropism for T cElls and skin, which is nEcEssary for its lifE cyclE in thE human host, rEquirEs this nonconsErvEd rEgion of thE N-tErminal rEgion of VZV gE.
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EssEntial Functions of thE UniquE N-TErminal REgion of thE VaricElla-ZostEr Virus GlycoprotEin E Ectodomain in Viral REplication and in thE PathogEnEsis of Skin InfEction
Journal of virology, 2006Co-Authors: Barbara Berarducci, Marvin Sommer, Minako Ikoma, Shaye Stamatis, Charles Grose, Ann M ArvinAbstract:VaricElla-zostEr virus (VZV) GlycoprotEin E (gE) is a multifunctional protEin important for cEll-cEll sprEad, EnvElopmEnt, and possibly Entry. In contrast to othEr alphahErpEsvirusEs, gE is EssEntial for VZV rEplication. IntErEstingly, thE N-tErminal rEgion of gE, comprisEd of amino acids 1 to 188, was shown not to bE consErvEd in thE othEr alphahErpEsvirusEs by bioinformatics analysis. Mutational analysis was pErformEd to invEstigatE thE functions associatEd with this uniquE gE N-tErminal rEgion. LinkEr insErtions, sErinE-to-alaninE mutations, and dElEtions wErE introducEd in thE gE N-tErminal rEgion in thE VZV gEnomE, and thE EffEcts of thEsE mutations on virus rEplication and cEll-cEll sprEad, gE trafficking and localization, virion formation, and rEplication in vivo in thE skin wErE analyzEd. In summary, mutagEnEsis of thE gE N-tErminal rEgion idEntifiEd a nEw functional rEgion in thE VZV gE Ectodomain EssEntial for cEll-cEll sprEad and thE pathogEnEsis of VZV skin tropism and dEmonstratEd that diffErEnt subdomains of thE uniquE N-tErminal rEgion had spEcific rolEs in viral rEplication, cEll-cEll sprEad, and sEcondary EnvElopmEnt.
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VaricElla-zostEr virus infEction facilitatEs VZV GlycoprotEin E trafficking to thE mEmbranE surfacE of mElanoma cElls.
Journal of medical virology, 2003Co-Authors: Jay Lee, Marvin H Sommer, Ann M ArvinAbstract:VaricElla-zostEr virus GlycoprotEin E (gE) is thE most abundant VZV GlycoprotEin on thE surfacE of virus-infEctEd cElls. VZV gE has targEting sEquEncEs for thE trans-Golgi nEtwork (TGN) and is transportEd from thE ER to thE TGN in infEctEd and gE-transfEctEd cElls. In this study, VZV gE ExprEssing mElanoma cEll linEs wErE gEnEratEd. gE is ExprEssEd undEr thE control of thE rEvErsE TEt rEprEssor (TEt-On). gE inducEd by TEt-On is rEtainEd at thE ER as wEll as in thE cis Golgi by immunofluorEscEncE confocal microscopy. To tEst whEthEr othEr viral protEin(s) may facilitatE gE trafficking and surfacE localization, MSPgE-vOka virus that contains MSPgE in placE of wt gE was madE. MAb 3B3 anti-gE doEs not bind to MSPgE. This MAb was usEd to track thE localization of gE in MEt-gE cElls post MSPgE-vOka infEction. gE bEcamE dEtEctablE mostly at thE TGN and on thE cEll surfacE aftEr viral infEction. ThEsE data indicatE that viral protEins facilitatE thE trafficking and cEll surfacE ExprEssion of gE.
M.j. Kaashoek - One of the best experts on this subject based on the ideXlab platform.
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EpitopEs on GlycoprotEin E and on thE GlycoprotEin E/GlycoprotEin I complEx of bovinE hErpEsvirus 1 arE ExprEssEd by all of 222 isolatEs and 11 vaccinE strains.
Archives of virology, 2000Co-Authors: Frans A.m. Rijsewijk, M.j. Kaashoek, J.p.m. Langeveld, M.a. Maris-veldhuis, Juana Magdalena, S. B. E. Verschuren, Rob H. Meloen, J.t. Van OirschotAbstract:GlycoprotEin E (gE) of bovinE hErpEsvirus 1 (BHV1) forms a complEx with GlycoprotEin I (gI) and plays an important rolE in cEll-to-cEll sprEad mEchanisms of thE virus, but is not EssEntial for propagation of thE virus. To study thE antigEnic variability of BHV1 GlycoprotEin E, a sEt of six wEll charactErisEd monoclonal antibodiEs (MAbs) was EstablishEd using BHV1 gE and gI dElEtion mutants, Eukaryotically ExprEssEd gE and gI and pEpscan analysis. Two of thEsE MAbs rEactEd with a linEar gE EpitopE (MAbs 3 and 52), two rEactEd with a morE conformation dEpEndEnt gE EpitopE (MAbs 61 and 81) and two rEactEd with EpitopEs formEd by a complEx formEd bEtwEEn gE and GlycoprotEin I (MAbs 67 and 75). With thEsE six MAbs thE gE ExprEssion of 222 BHV1 isolatEs and 11 BHV1 modifiEd-livE vaccinE strains was studiEd in vitro, using an immunopEroxidasE monolayEr assay. All 222 BHV1 isolatEs and 11 vaccinE strains wErE found to rEact with MAbs 61, 81 and 75. ThrEE of thE 222 isolatEs failEd to rEact with MAb 67 and two of thE vaccinEs rEactEd vEry wEakly with MAbs 3 and 52. Analysis of thE gE gEnEs of thEsE fivE abErrant isolatEs and thE gE GlycoprotEins thEy ExprEssEd, did not show obvious sizE diffErEncEs comparEd to wild-typE BHV1. WE concludE that thE tEstEd gE EpitopEs arE highly consErvEd, including thE EpitopEs formEd by thE gI/gE complEx.
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VirulEncE and immunogEnicity in calvEs of thymidinE kinasE- and GlycoprotEin E-nEgativE bovinE hErpEsvirus 1 mutants
Veterinary microbiology, 1996Co-Authors: M.j. Kaashoek, Frans A.m. Rijsewijk, F.a.c. Van Engelenburg, A. Moerman, A. L. J. Gielkens, J.t. Van OirschotAbstract:A dElEtion was introducEd into thE thymidinE kinasE (TK) gEnE of thE BHV1 strain Lam and, or, thE complEtE coding rEgion of thE GlycoprotEin E (gE) gEnE was dElEtEd to rEducE virulEncE and to makE sErological diffErEntiation possiblE. ThE virulEncE and immunogEnicity of thEsE thrEE BHV1 mutants (TK−, gE− and TK−gE−) wErE studiEd in spEcific-pathogEn-frEE calvEs. Although inactivation of TK strongly rEducEd thE virulEncE of thE Lam strain, dElEtion of thE gE gEnE alonE sufficEd to yiEld complEtE attEnuation of thE Lam strain for sEvEn-wEEk-old calvEs. ThE thrEE mutants inducEd protEctivE immunity against disEasE aftEr challEngE with a virulEnt BHV1 strain. ThE rEduction of virus shEdding aftEr challEngE was rElatEd to thE virulEncE of thE various strains. ThE immunogEnicity of thE mutants was also EvidEncEd by thE rEduction of challEngE virus shEdding aftEr dExamEthasonE trEatmEnt. NonE of thE mutant virusEs could bE isolatEd aftEr dExamEthasonE trEatmEnt. ThE rEsults dEmonstratE that thE gE− and TK−gE− mutants arE good candidatEs for incorporation in a BHV1 markEr vaccinE.
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an inactivatEd vaccinE basEd on a GlycoprotEin E nEgativE strain of bovinE hErpEsvirus 1 inducEs protEctivE immunity and allows sErological diffErEntiation
Vaccine, 1995Co-Authors: M.j. Kaashoek, A. Moerman, J. Madic, F A M Rijsewijk, K Weerdmeester, M A Marisveldhuis, J.t. Van OirschotAbstract:ThE bovinE hErpEsvirus 1 (BHV1) strain Za is a convEntionally attEnuatEd strain with a 2.7 kb dElEtion that EncompassEs thE complEtE coding rEgion for GlycoprotEin E (gE). This gE-nEgativE strain was usEd as wholE-virus antigEn in an inactivatEd virus vaccinE. ThrEE diffErEnt antigEn concEntrations of this vaccinE wErE EvaluatEd for safEty and Efficacy in a vaccination-challEngE ExpErimEnt in calvEs. No advErsE EffEcts wErE obsErvEd in any of thE calvEs vaccinatEd with thE gE-nEgativE vaccinEs. CalvEs givEn thE vaccinE with thE highEst antigEn concEntration wErE adEquatEly protEctEd against challEngE; clinical symptoms wErE virtually absEnt and challEngE virus shEdding was significantly rEducEd as comparEd with unvaccinatEd calvEs. WE dEvElopEd a sEnsitivE blocking EnzymE-linkEd immunosorbEnt assay (ELISA) to dEtEct antibodiEs against gE. AftEr vaccination, calvEs did not producE antibodiEs against gE, but thEsE antibodiEs wErE dEtEctablE within 2 wEEks aftEr challEngE both in vaccinatEd and in unvaccinatEd calvEs. ThEsE rEsults dEmonstratE thE Efficacy of a gE-nEgativE inactivatEd BHV1 vaccinE and thE dEtEctability of antibodiEs against gE aftEr infEction. ThE combinEd usE of thE markEr vaccinE and thE gE-blocking ELISA makEs it possiblE to diffErEntiatE bEtwEEn vaccinatEd animals and infEctEd animals. This possibility may bE vEry usEful in BHV1 control programmEs.
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A GlycoprotEin E dElEtion mutant of bovinE hErpEsvirus 1 is avirulEnt in calvEs.
Journal of General Virology, 1994Co-Authors: F.a.c. Van Engelenburg, Frans A.m. Rijsewijk, M.j. Kaashoek, L. Van Den Burg, A. Moerman, A. L. J. Gielkens, J.t. Van OirschotAbstract:A markEr vaccinE Elicits an antibody rEsponsE in thE host that can bE distinguishEd from thE antibody rEsponsE inducEd by a wild-typE strain. To obtain a bovinE hErpEsvirus 1 (BHV-1) markEr vaccinE, wE constructEd a GlycoprotEin E (gE) dElEtion mutant. This was obtainEd by rEmoving thE complEtE gE coding rEgion from thE BHV-1 gEnomE. To attEnuatE thE gE dElEtion mutant furthEr, wE also introducEd a small dElEtion in thE thymidinE kinasE (TK) gEnE. WE sElEctEd thrEE mutants: thE gE dElEtion mutant, a TK dElEtion mutant and a gE/TK doublE dElEtion mutant, and ExaminEd thEir virulEncE and immunogEnicity in calvEs. AftEr intranasal inoculation, thE TK dElEtion mutant showEd somE rEsidual virulEncE, whErEas thE gE and gE/TK dElEtion mutants wErE avirulEnt. ThE calvEs inoculatEd with thE dElEtion mutants wErE protEctEd against disEasE aftEr challEngE ExposurE and shEd significantly lEss virus than control calvEs. DElEting thE gE gEnE, thErEforE, has littlE EffEct on thE immunogEnicity of BHV-1, but is sufficiEnt to rEducE thE virulEncE of BHV-1 in calvEs. ThEsE findings lEd us to concludE that thE gE dElEtion mutant is a good candidatE for a modifiEd livE BHV-1 markEr vaccinE.
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A convEntionally attEnuatEd GlycoprotEin E-nEgativE strain of bovinE hErpEsvirus typE 1 is an Efficacious and safE vaccinE
Vaccine, 1994Co-Authors: M.j. Kaashoek, Frans A.m. Rijsewijk, A. Moerman, A. L. J. Gielkens, J. Madic, J. Quak, J.t. Van OirschotAbstract:WE ExaminEd thE vaccinE propErtiEs of a convEntionally attEnuatEd bovinE hErpEsvirus typE 1 (BHV-1) mutant strain A. This strain has a dElEtion that EncompassEs thE GlycoprotEin E gEnE and may thErEforE bE usEd as a markEr vaccinE. WE comparEd strain A with a commErcial livE BHV-1 vaccinE B. CalvEs wErE intranasally vaccinatEd with strain A or with vaccinE B. Strain A was virtually avirulEnt for young calvEs. AftEr challEngE, vaccinatEd calvEs wErE protEctEd against disEasE and virus shEdding was considErably rEducEd. AftEr dExamEthasonE trEatmEnt, strain A was not rEcovErEd, whErEas vaccinE B and challEngE virus wErE. WE concludE that strain A is suitablE for inclusion in a vaccinE and has thE potEntial advantagE of bEing usEd as a markEr vaccinE.
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Isolation of a GlycoprotEin E-dElEtEd bovinE hErpEsvirus typE 1 strain in thE fiEld
The Veterinary record, 2003Co-Authors: Marc Dispas, Mylène Lemaire, Etienne Thiry, Frédéric Schynts, Carine Letellier, Emmanuel Vanopdenbosch, Pierre KerkhofsAbstract:During a fiEld trial to EvaluatE thE Efficacy of rEpEatEd vaccinations with bovinE hErpEsvirus typE 1 (BHV-1) markEr vaccinEs, a GlycoprotEin E (gE)-nEgativE BHV-1 strain was isolatEd from thE nasal sEcrEtions of two cows, Eight months aftEr vaccination with a gE-nEgativE livE-attEnuatEd vaccinE, initially givEn intranasally, thEn intramuscularly. ThE strain isolatEd was charactErisEd using immunofluorEscEncE, rEstriction analysis and CR. All thE tEchniquEs usEd idEntifiEd thE isolatEd virus as a gE-nEgativE BHV-1 phEnotypically and gEnotypically idEntical to thE Za strain usEd as a control.
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LatEncy and rEactivation of a GlycoprotEin E nEgativE bovinE hErpEsvirus typE 1 vaccinE: influEncE of virus load and EffEct of spEcific matErnal antibodiEs
Vaccine, 2001Co-Authors: Mylène Lemaire, Gilles Meyer, Frédéric Schynts, Sándor Belák, Jean-pierre Georgin, Eric Baranowski, Annick Gabriel, Etienne ThiryAbstract:ThE EffEcts of thE vaccination of nEonatal calvEs with a GlycoprotEin E (gE)-nEgativE bovinE hErpEsvirus typE 1 (BHV-1) wErE invEstigatEd in naïvE and passivEly immunisEd calvEs EithEr with thE rEcommEndEd dosE or a 5-fold concEntratEd onE. AftEr inoculation (PI), all calvEs ExcrEtEd thE virus vaccinE ExcEpt thrEE passivEly immunisEd calvEs inoculatEd with thE lowEr titrE. No antibody rEsponsE could bE dEtEctEd in passivEly immunisEd calvEs, whatEvEr thE dosE usEd, and thEy all bEcamE BHV-1 sEronEgativE and rEmainEd so aftEr dExamEthasonE trEatmEnt (PDT). NEvErthElEss, as shown by a gamma-intErfEron assay, all calvEs that ExcrEtEd thE vaccinE PI dEvElopEd a cEll-mEdiatEd immunE rEsponsE and a boostEr rEsponsE was obsErvEd PDT, suggEsting viral rEactivation. ThE vaccinE virus was rEcovErEd PDT from nasal sEcrEtions in two calvEs and BHV-1 DNA wErE dEtEctEd in trigEminal ganglia from fivE calvEs bElonging to all inoculatEd groups. ThE rEsults show that thE BHV-1 gE-nEgativE vaccinE can Establish latEncy not only in naïvE but also in passivEly immunisEd nEonatal calvEs aftEr a singlE intranasal inoculation. MorEovEr, this study shows for thE first timE that thE gE-nEgativE vaccinE, whEn usEd in passivEly immunisEd calvEs, can lEad to sEronEgativE vaccinE virus carriErs.
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LatEncy and rEactivation of a GlycoprotEin E nEgativE bovinE hErpEsvirus typE 1 vaccinE: influEncE of virus load and EffEct of spEcific matErnal antibodiEs
Vaccine, 2001Co-Authors: Mylène Lemaire, Gilles Meyer, Frédéric Schynts, Carlos Ros, Sándor Belák, Jean-pierre Georgin, Eric Baranowski, Annick Gabriel, Etienne ThiryAbstract:ThE EffEcts of thE vaccination of nEonatal calvEs with a GlycoprotEin E (gE)-nEgativE bovinE hErpEsvirus typE 1 (BHV-1) wErE invEstigatEd in naïvE and passivEly immunisEd calvEs EithEr with thE rEcommEndEd dosE or a 5-fold concEntratEd onE. AftEr inoculation (PI), all calvEs ExcrEtEd thE virus vaccinE ExcEpt thrEE passivEly immunisEd calvEs inoculatEd with thE lowEr titrE. No antibody rEsponsE could bE dEtEctEd in passivEly immunisEd calvEs, whatEvEr thE dosE usEd, and thEy all bEcamE BHV-1 sEronEgativE and rEmainEd so aftEr dExamEthasonE trEatmEnt (PDT). NEvErthElEss, as shown by a gamma-intErfEron assay, all calvEs that ExcrEtEd thE vaccinE PI dEvElopEd a cEll-mEdiatEd immunE rEsponsE and a boostEr rEsponsE was obsErvEd PDT, suggEsting viral rEactivation. ThE vaccinE virus was rEcovErEd PDT from nasal sEcrEtions in two calvEs and BHV-1 DNA wErE dEtEctEd in trigEminal ganglia from fivE calvEs bElonging to all inoculatEd groups. ThE rEsults show that thE BHV-1 gE-nEgativE vaccinE can Establish latEncy not only in naïvE but also in passivEly immunisEd nEonatal calvEs aftEr a singlE intranasal inoculation. MorEovEr, this study shows for thE first timE that thE gE-nEgativE vaccinE, whEn usEd in passivEly immunisEd calvEs, can lEad to sEronEgativE vaccinE virus carriErs.
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SpEcific passivE immunity rEducEs thE ExcrEtion of GlycoprotEin E-nEgativE bovinE hErpEsvirus typE 1 vaccinE strain in calvEs.
Vaccine, 2000Co-Authors: Mylène Lemaire, Frédérick Schynts, Gilles Meyer, E Hanon, Etienne ThiryAbstract:WE invEstigatEd thE ExcrEtion of EithEr a GlycoprotEin E (gE)-nEgativE bovinE hErpEsvirus typE 1 (BHV1) vaccinE strain or a convEntional modifiEd-livE vaccinE strain in both naïvE and passivEly immunisEd calvEs. ThE rEplication of gE-nEgativE strain was considErably rEducEd in thE matErnally immunisEd calvEs, in comparison with thE non-immunE calvEs. On thE othEr hand, thE ExcrEtion of thE gE-positivE convEntional vaccinE strain was not rEducEd and EvEn sEEmEd to bE prolongEd in thE prEsEncE of matErnal antibodiEs. ThEsE rEsults suggEst that BHV1 gE may play a rolE in virus survival in thE prEsEncE of antibodiEs.
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Antibody rEsponsE to GlycoprotEin E aftEr bovinE hErpEsvirus typE 1 infEction in passivEly immunisEd, GlycoprotEin E-nEgativE calvEs.
The Veterinary record, 1999Co-Authors: Mylène Lemaire, Frédérick Schynts, Gilles Meyer, Etienne ThiryAbstract:This study was conductEd to dEtErminE whEthEr young calvEs with matErnal antibodiEs against bovinE hErpEsvirus typE 1 (BHV-1) but without antibodiEs against GlycoprotEin E (gE) can producE an activE antibody rEsponsE to gE aftEr a BHV-1 infEction. FivE calvEs rEcEivEd at birth colostrum from gE-sEronEgativE cows which had bEEn vaccinatEd two or thrEE timEs with an inactivatEd BHV-1, gE-dElEtEd markEr vaccinE. AftEr inoculation with a wild-typE virulEnt strain of BHV-1, all thE passivEly immunisEd gE-nEgativE calvEs shEd virus in largE amounts in thEir nasal sEcrEtions. All thE calvEs sEroconvErtEd to gE within two to four wEEks aftEr inoculation and thEn had high lEvEls of gE antibodiEs for at lEast four months. ThE dEvElopmEnt of an activE cEll-mEdiatEd immunE rEsponsE was also dEtEctEd by in vitro BHV-1-spEcific intErfEron-gamma assays. All thE calvEs wErE latEntly infEctEd, bEcausE onE of thEm rE-ExcrEtEd thE virus spontanEously and thE othEr four did so aftEr bEing trEatEd with dExamEthasonE. ThE rEsults showEd that undEr thE conditions of this work thE gE-nEgativE markEr could also distinguish bEtwEEn passivEly immunisEd and latEntly infEctEd calvEs.