Field evaluation of safety during gestation and horizontal spread of a recombinant differential bovine herpesvirus 1 (BoHV-1) vaccine

Abstract

Bovine herpesvirus type 1 (BoHV-1) is recognized as a major cause of respiratory, reproductive disease and abortion in cattle. Vaccination is widely applied to minimize losses induced by BoHV-1 infections; however, vaccination of dams during pregnancy with modified live virus (MLV) vaccines has been occasionally associated to abortions. We have previously reported the development of a BoHV-1 recombinant virus, constructed with basis on a Brazilian BoHV-1 (Franco et al. 2002a) from which the gene coding for glycoprotein E (gE) was deleted (gE-) by genetic manipulation. Such recombinant has been previously evaluated in its potential as a differential vaccine (gE- vaccine) that allows differentiation between vaccinated and infected animals. Here, in the first part of the present study, the safety of the gE- vaccine during pregnancy was evaluated by the intramuscular inoculation of 10(7.4) tissue culture 50 % infective doses (TCID50) of the virus into 22 pregnant dams (14 BoHV-1 seronegative; 8 seropositive), at different stages of gestation. Other 15 pregnant dams were kept as non-vaccinated controls. No abortions, stillbirths or fetal abnormalities were seen after vaccination. Seroconversion was observed in both groups of previously seronegative vaccinated animals. In the second part of the study, the potential of the gE- vaccine virus to spread among beef cattle under field conditions was examined. Four heifers were inoculated intranasally with a larger amount (10(7,6) TCID50) of the gE- vaccine (to increase chances of transmission) and mixed with other sixteen animals at the same age and body condition, in the same grazing area, at a population density equal to the average cattle farming density within the region (one cattle head per 10,000 m²), for 180 days. All animals were monitored daily for clinical signs. Serum samples were collected on days 0, 30, 60 and 180 post-vaccination. Seroconversion was observed only in vaccinated heifers. These results indicate that, under the conditions of the present study, the gE- vaccine virus did not cause any noticeable harmful effect on pregnant dams and on its offspring and did not spread horizontally among cattle.

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

“…Moreover, attempts to reactivate latent infection in two IV-vaccinated heifers by Dx administration failed, indicating that the recombinant virus does not reactivate efficiently from latency. The Brazilian SV265gE-strain has been previously shown to be attenuated for calves after intranasal (IN) and IM inoculation (Franco et al 2002b), safe for pregnant cows (Spilki et al 2005) and would confer clinical protection to calves upon vaccination followed by IN virus challenge (Franco et al 2002b). Taken together, these results are promising towards the use of this recombinant strain for local immunization aiming at reducing the losses associated with BoHV-1 genital infection in the field.…”

“…Although Brazil and most South American countries have not yet embarked on BoHV-1 eradication programs, the use of differential vaccines (still insipient) represents an attractive strategy for herd certification through animal trade and/or export (Brum et al 2009). The safety and attenuation of the vaccine strain SV265gE-for calves and pregnant cows also represent an advantage over other vaccine strains available (Franco et al 2002b;Spilki et al 2005). In addition to an expected solid local immune response, genital immunization may also provide mucosal immunity able to protect against IN challenge (Kit et al 1986).…”

“…The cells were cultured on minimal essential medium (MEM), containing ampicillin (1.6mg/L), streptomycin (0.4mg/L), amphotericin (2mg/L), supplemented with 10% fetal bovine serum 6 . The production and characterization of the vaccine candidate strain SV-265gE-has been described previously (Franco et al 2002a, Spilki et al 2005. The virus used for challenge (SV-56/ 90) was isolated from an outbreak of balanoposthitis in bulls in Southern Brazil (Weiblen et al 1992) and subsequently characterized as belonging to BoHV-1.2 subtype (D'Arce et al 2002).…”

“…This recombinant virus was subsequently shown to be attenuated for calves after IN and intramuscular (IM) administration and conferred protection against homologous virus challenge (Franco et al 2002b). Subsequent studies investigated the transmission of this virus under field conditions and demonstrated its safety for pregnant cows (Spilki et al 2005).…”

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

“…Several efforts have been made to produce and to make commercially available BoHV-1 marker vaccines in Brazil (Franco et al 2002a, 2002b, Spilki et al 2005. 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.…”