Safety and immunogenicity of a glycoprotein E gene-deleted bovine herpesvirus 1 strain as a candidate vaccine strain

ABSTRACT: A glycoprotein E-deleted Brazilian bovine herpesvirus 1 (BoHV-1gEΔ) was tested regarding to safety and immunogenicity. Intramuscular inoculation of young calves with a high virus dose did not result in clinical signs or virus shedding during acute infection or after dexamethasone administration. Calves vaccinated once IM (group I) or subcutaneously (group II) with live BoHV-1gEΔ or twice with inactivated virus plus aluminum hydroxide (group IV) or Montanide™ (group V) developed VN titers of 2 to 8 (GMT:2); 2 to 4 (GMT:1.65); 2 to 16 (GMT:2.45) and 2 to 128 (GMT:3.9), respectively. All BoHV-1gEΔ vaccinated calves remained negative in an anti-gE ELISA. Lastly, six young calves vaccinated with live BoHV-1gEΔ and subsequently challenged with a virulent BoHV-1 strain shed less virus and developed only mild and transient nasal signs comparing to unvaccinated calves. Thus, the recombinant BoHV-1gEΔ is safe and immunogenic for calves and allows for serological differentiation by a gE-ELISA test.

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A Mutation in the Latency-Related Gene of Bovine Herpesvirus 1 Disrupts the Latency Reactivation Cycle in Calves

Journal of Virology ◽

10.1128/jvi.76.13.6771-6779.2002 ◽

2002 ◽

Vol 76 (13) ◽

pp. 6771-6779 ◽

Cited By ~ 58

Author(s):

Melissa Inman ◽

Luciane Lovato ◽

Alan Doster ◽

Clinton Jones

Keyword(s):

Infectious Virus ◽

Acute Infection ◽

Bovine Herpesvirus ◽

Pcr Analysis ◽

Trigeminal Ganglia ◽

Viral Transcript ◽

Bovine Herpesvirus 1 ◽

Virus Shedding ◽

Latently Infected ◽

Herpesvirus 1

ABSTRACT Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is usually initiated via the ocular or nasal cavity. Following acute infection, the primary site for BHV-1 latency is the sensory neuron. Reactivation from latency occurs sporadically, resulting in virus shedding and transmission to uninfected cattle. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, suggesting that it mediates some aspect of latency. An LR mutant was constructed by inserting three stop codons near the beginning of the LR-RNA, suggesting that expression of LR proteins would be altered. The LR mutant grew with wild-type (wt) efficiency in bovine kidney cells (MDBK). When calves were infected with the LR mutant, a dramatic decrease (3 to 4 logs) in ocular, but not nasal, viral shedding occurred during acute infection relative to the wt or the LR-rescued virus (M. Inman, L. Lovato, A. Doster, and C. Jones, J. Virol. 75:8507-8515, 2001). In this study, we examined the latency reactivation cycle in calves infected with the LR mutant and compared these results to those from calves infected with wt BHV-1 or the LR-rescued virus. During acute infection, lower levels of infectious virus were detected in trigeminal ganglion homogenates from calves infected with the LR mutant. As judged by in situ hybridization, BHV-1-positive neurons were detected in trigeminal ganglia of calves infected with the wt but not the LR mutant. Although LR-RNA was detected by reverse transcription-PCR in calves latently infected with the LR mutant, a semiquantitative PCR analysis revealed that lower levels of viral DNA were present in trigeminal ganglia of calves infected with the LR mutant. Dexamethasone treatment of calves latently infected with wt BHV-1 or the LR-rescued virus, but not the LR mutant, consistently induced reactivation from latency, as judged by shedding of infectious virus from the nose or eyes and increases in BHV-1-specific antibodies. In summary, this study demonstrates that wt expression of LR gene products plays an important role in the latency reactivation cycle of BHV-1 in cattle.

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EvaGreen-based Multiplex Real-time PCR Assay for Rapid Differentiation of Wild-Type and Glycoprotein E-Deleted Bovine Herpesvirus-1 Strains

Animal Biotechnology ◽

10.1080/10495398.2016.1268620 ◽

2017 ◽

Vol 28 (4) ◽

pp. 248-252 ◽

Cited By ~ 1

Author(s):

Sachin S. Pawar ◽

Chetan D. Meshram ◽

Niraj K. Singh ◽

Mohini Saini ◽

B. P. Mishra ◽

...

Keyword(s):

Real Time ◽

Real Time Pcr ◽

Bovine Herpesvirus ◽

Wild Type ◽

Pcr Assay ◽

Bovine Herpesvirus 1 ◽

Glycoprotein E ◽

Herpesvirus 1

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A Brazilian glycoprotein E-negative bovine herpesvirus type 1.2a (BHV-1.2a) mutant is attenuated for cattle and induces protection against wild-type virus challenge

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2002000400002 ◽

2002 ◽

Vol 22 (4) ◽

pp. 135-140 ◽

Cited By ~ 13

Author(s):

Ana Cláudia Franco ◽

Fernando Rosado Spilki ◽

Paulo Augusto Esteves ◽

Marcelo de Lima ◽

Rudi Weiblen ◽

...

Keyword(s):

Clinical Signs ◽

Bovine Herpesvirus ◽

Vaccine Virus ◽

Parental Virus ◽

Wild Type Virus ◽

Wild Type ◽

Glycoprotein E ◽

Virus Shedding ◽

Virus Challenge ◽

Herpesvirus Type

The authors previously reported the construction of a glycoprotein E-deleted (gE-) mutant of bovine herpesvirus type 1.2a (BHV-1.2a). This mutant, 265gE-, was designed as a vaccinal strain for differential vaccines, allowing the distinction between vaccinated and naturally infected cattle. In order to determine the safety and efficacy of this candidate vaccine virus, a group of calves was inoculated with 265gE-. The virus was detected in secretions of inoculated calves to lower titres and for a shorter period than the parental virus inoculated in control calves. Twenty one days after inoculation, the calves were challenged with the wild type parental virus. Only mild signs of infection were detected on vaccinated calves, whereas non-vaccinated controls displayed intense rhinotracheitis and shed virus for longer and to higher titres than vaccinated calves. Six months after vaccination, both vaccinated and control groups were subjected to reactivation of potentially latent virus. The mutant 265gE- could not be reactivated from vaccinated calves. The clinical signs observed, following the reactivation of the parental virus, were again much milder on vaccinated than on non-vaccinated calves. Moreover, parental virus shedding was considerably reduced on vaccinated calves at reactivation. In view of its attenuation, immunogenicity and protective effect upon challenge and reactivation with a virulent BHV-1, the mutant 265gE- was shown to be suitable for use as a BHV-1 differential vaccine virus.

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A glycoprotein E gene-deleted bovine herpesvirus 1 as a candidate vaccine strain

Brazilian Journal of Medical and Biological Research ◽

10.1590/1414-431x20154243 ◽

2015 ◽

Vol 48 (9) ◽

pp. 843-851 ◽

Cited By ~ 2

Author(s):

M. Weiss ◽

M.C.S. Brum ◽

D. Anziliero ◽

R. Weiblen ◽

E.F. Flores

Keyword(s):

Vaccine Strain ◽

Bovine Herpesvirus ◽

Candidate Vaccine ◽

Bovine Herpesvirus 1 ◽

Glycoprotein E ◽

E Gene ◽

Herpesvirus 1

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Efficacy of a live glycoprotein E-negative bovine herpesvirus 1 vaccine in cattle in the field

Vaccine ◽

10.1016/s0264-410x(00)00435-7 ◽

2001 ◽

Vol 19 (15-16) ◽

pp. 1924-1930 ◽

Cited By ~ 37

Author(s):

M.H Mars ◽

M.C.M de Jong ◽

P Franken ◽

J.T van Oirschot

Keyword(s):

Bovine Herpesvirus ◽

Bovine Herpesvirus 1 ◽

Glycoprotein E ◽

Herpesvirus 1

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A live attenuated glycoprotein E negative bovine herpesvirus 1 vaccine induces a partial cross-protection against caprine herpesvirus 1 infection in goats

Veterinary Microbiology ◽

10.1016/j.vetmic.2005.11.001 ◽

2006 ◽

Vol 113 (3-4) ◽

pp. 303-308 ◽

Cited By ~ 12

Author(s):

Julien Thiry ◽

Maria Tempesta ◽

Michele Camero ◽

Elvira Tarsitano ◽

Anna Lucia Bellacicco ◽

...

Keyword(s):

Bovine Herpesvirus ◽

Cross Protection ◽

Bovine Herpesvirus 1 ◽

Glycoprotein E ◽

Herpesvirus 1

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Changes in the bovine herpesvirus 1 genome during acute infection, after reactivation from latency, and after superinfection in the host animal

Archives of Virology ◽

10.1007/bf01313957 ◽

1989 ◽

Vol 106 (3-4) ◽

pp. 261-279 ◽

Cited By ~ 13

Author(s):

C. A. Whetstone ◽

J. M. Miller ◽

D. M. Bortner ◽

M. J. Van Der Maaten

Keyword(s):

Acute Infection ◽

Bovine Herpesvirus ◽

Host Animal ◽

Bovine Herpesvirus 1 ◽

Herpesvirus 1

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Intraspecific bovine herpesvirus 1 recombinants carrying glycoprotein E deletion as a vaccine marker are virulent in cattle

Journal of General Virology ◽

10.1099/vir.0.81969-0 ◽

2006 ◽

Vol 87 (8) ◽

pp. 2149-2154 ◽

Cited By ~ 17

Author(s):

Benoît Muylkens ◽

François Meurens ◽

Frédéric Schynts ◽

Frédéric Farnir ◽

Aldo Pourchet ◽

...

Keyword(s):

High Frequency ◽

Bovine Herpesvirus ◽

Clinical Score ◽

Natural Host ◽

Field Strain ◽

Bovine Herpesvirus 1 ◽

Glycoprotein E ◽

Control Programmes ◽

Herpesvirus 1

Vaccines used in control programmes of Bovine herpesvirus 1 (BoHV-1) utilize highly attenuated BoHV-1 strains marked by a deletion of the glycoprotein E (gE) gene. Since BoHV-1 recombinants are obtained at high frequency in experimentally coinfected cattle, the consequences of recombination on the virulence of gE-negative BoHV-1 were investigated. Thus, gE-negative BoHV-1 recombinants were generated in vitro from several virulent BoHV-1 and one mutant BoHV-1 deleted in the gC and gE genes. Four gE-negative recombinants were tested in the natural host. All the recombinants were more virulent than the gE-negative BoHV-1 vaccine and the gC- and gE-negative parental BoHV-1. The gE-negative recombinant isolated from a BoHV-1 field strain induced the highest severe clinical score. Latency and reactivation studies showed that three of the recombinants were reexcreted. Recombination can therefore restore virulence of gE-negative BoHV-1 by introducing the gE deletion into a different virulence background.

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