Genital immunization of heifers with a glycoprotein Edeleted, recombinant bovine herpesvirus 1 strain confers protection upon challenge with a virulent isolate

Abstract

ABSTRACT.-Weiss M., Vogel F.S.F., Martins M., Weiblen R., Roehe P.M., Franco A.C. & Flores E.F. 2010. Genital immunization of heifers with a glycoprotein E-deleted, recombinant bovine herpesvirus 1 strain confers protection upon challenge with a virulent isolate. Pesquisa Veterinária Brasileira 30(1):42-50. Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. E-mail: eduardofurtadoflores@gmail.com Venereal infection of seronegative heifers and cows with bovine herpesvirus type 1.2 (BoHV-1.2) frequently results in vulvovaginitis and transient infertility. Parenteral immunization with inactivated or modified live BoHV-1 vaccines often fails in conferring protection upon genital challenge. We herein report an evaluation of the immune response and protection conferred by genital vaccination of heifers with a glycoprotein E-deleted recombinant virus (SV265gE-). A group of six seronegative heifers was vaccinated with SV265gE-(0,2mL containing 10 6.9 TCID 50 ) in the vulva submucosa (group IV); four heifers were vaccinated intramuscularly (group IM, 1mL containing 10 7.6 TCID 50 ) and four heifers remained as non-vaccinated controls. Heifers vaccinated IV developed mild, transient local edema and hyperemia and shed low amounts of virus for a few days after vaccination, yet a sentinel heifer maintained in close contact did not seroconvert. Attempts to reactivate the vaccine virus in two IV vaccinated heifers by intravenous administration of dexamethasone (0.5mg/kg) at day 70 pv failed since no virus shedding, recrudescence of genital signs or seroconversion were observed. At day 70 pv, all vaccinated and control heifers were challenged by genital inoculation of a highly virulent BoHV-1.2 isolate (SV-56/90, 10 7.1 TCID 50 /animal). After challenge, virus shedding was detected in genital secretions of control animals for 8.2 days (8-9); in the IM group for 6.2 days (4-8 days) and during 5.2 days (5-6 days) in the IV group. Control non-vaccinated heifers developed moderate (2/4) or severe (2/4) vulvovaginitis lasting 9 to 13 days (x: 10.7 days). The disease was characterized by vulvar edema, vulvo-vestibular congestion, vesicles progressing to coalescence and erosions, fibrino-necrotic plaques and fibrinopurulent exudate. IM vaccinated heifers developed mild (1/3) or moderate (3/4) genital lesions, lasting 10 to 12 days (x: 10.7 days); and IV vaccinated heifers developed mild and transient vulvovaginitis (3/4) or mild to moderate genital lesions (1/4). In the IV group, the clinical signs lasted 4 to 8 days (x: 5.5 days). Clinical examination of the animals after challenge revealed that vaccination by both routes conferred some degree of protection, yet IV vaccination was clearly more effective in reducing the severity and duration of clinical 2) pode resultar em vulvovaginite e infertilidade temporária. As vacinas atenuadas ou inativadas administradas pela via parenteral freqüente-mente conferem proteção incompleta frente a desafio pela via genital. Este...

A recombinant bovine herpesvirus 5 defective in thymidine kinase and glycoprotein E is attenuated and immunogenic for calves

“…None of the vaccinated/inoculated animals produced antibodies to gE, even when tested a long time after vaccination, and also after a boost immunization. In contrast, most calves vaccinated IM with an inactivated vaccine containing the parental virus (Brum et al 2010b) or immunized/inoculated with the live parental virus or with a gE-deleted BoHV-1 seroconverted to gE after 30 or 40 days (Brum et al 2010b, Weiss et al 2010. Thus, the serological response induced by the recombinant virus is gE-ELISA differentiable from that induced by infection or immunization with the whole, inactivated or live virus.…”

“…A gE-deleted BoHV-1 recombinant strain was constructed out a Brazilian BoHV-1.2 isolate (Franco et al 2002a). The recombinant was attenuated for cattle and induced protection against BoHV-1 by intranasal (Franco et al 2002b) and genital challenge (Weiss et al 2010). Recently, a double deletion mutant, defective in the glycoprotein (gE) and thymidine kinase (tk) genes was constructed out of a neurovirulent, well characterized Brazilian BoHV-5 strain (Brum et al 2010a).…”

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

“…Serum samples obtained at different times after virus inoculation or immunization were tested for virus neutralizing (VN) antibodies against BoHV-1 by virus neutralization assay, using the parental virus as the challenge virus (Weiss et al 2010). Titers were expressed as the reciprocal of the highest dilution that prevented virus replication, were transformed in geometric mean titers (GMT -log 2 ) for the calculation of the mean antibody titers of each group (Thrusfield 1986).…”

“…A gE-negative BoHV-1 strain has been constructed and evaluated regarding to safety, immunogenicity and potential serological differentiation (Spilki et al 2005, Weiss et al 2010. A gE and thymidine kinase (TK) double deletion BoHV-5 recombinant strain was constructed and proposed as a candidate vaccine strain (Brum et al 2010b).…”

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

“…Efforts to produce commercially viable BoHV-1 marker vaccines have long been reported in Brazil ( 19 , 20 ). A gE-negative BoHV-1 strain was constructed and evaluated in terms of safety, immunogenicity and potential serological differentiation ( 21 , 22 ). More recently, a gE and thymidine kinase double deletion BoHV-5 recombinant strain was constructed and proposed as a candidate vaccine strain (14).…”