Biologically safe, non-transmissible pseudorabies virus vector vaccine protects pigs against both Aujeszky's disease and classical swine fever (original) (raw)

A Study of the Ability of a TK-Negative and gI/gE-Negative Pseudorabies Virus (PRV) Mutant Inoculated by Different Routes to Protect Pigs Against PRV Infection

Journal of Veterinary Medicine, Series B, 2008

The capacity of a TK-negative (TK-) and gI/gE-negative (gI/gE-) pseudorabies virus (PRV) mutant to protect pigs against Aujeszky's disease carried out by experimental infection with a virulent PRV strain, was tested. There were three groups, each of four susceptible pigs which were inoculated twice by two different schedules. Group 1 received the modified virus by the intradermal (first inoculation)-intramuscular (second inoculation) routes; group 2 was treated by the intranasal (first inoculation)-intramuscular (second inoculation) routes. The third group was left untreated as the control. All of the pigs were challenged intranasally with a virulent PRV strain and they were subsequently injected with dexamethasone. Two pigs in each group were necropsied on days 5 and 15 after dexamethasone inoculation. The challenge exposure resulted in mild clinical signs, increase in growth and a shorter period of virus shedding in vaccinated pigs, whereas the control group showed severe signs of Aujeszky's disease. No difference in the titre of the virulent virus which was excreted by pigs of all three groups, was observed and all animals seroconverted. Both the mutant strain and the wild-type virus established a latent infection although only the latter was reactivated and shed. Slight lesions were observed in target tissues of the vaccinated animals and no significant differences were detected between the two inoculation schedules.

Vaccination of pigs against pseudorabies virus with plasmid DNA encoding glycoprotein D

Vaccine, 1999

We analysed the ability of a plasmid carrying the gene encoding glycoprotein D (gD) of pseudorabies virus (PRV) to induce humoral and cell-mediated immune responses and assessed the protection provided by PRV-gD DNA vaccination against challenge infection with PRV. Immunization with plasmid PRV-gD induced neutralizing antibodies and lymphocyte proliferative responses both in mice and pigs. Moreover, when challenged with virulent PRV six weeks following the last immunization, PRV-gD DNA vaccinated pigs excreted virus for a signi®cantly shorter period and showed less clinical symptoms than pigs vaccinated with a control plasmid. Thus, in the target animal, DNA vaccination with PRV-gD DNA induces protective immunity against challenge infection. #

Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge

a b s t r a c t Pseudorabies (PR) or Aujeszky's disease (AD), caused by pseudorabies virus (PRV), is an economically important viral disease in many countries. The modified live vaccine Bartha-K61 strain has played an important role in the control of PR in many countries including China. Since late 2011, however, increasing PR outbreaks caused by an emerging PRV variant have been reported in Bartha-K61-vaccinated swine population on many farms in China. Previously, we showed that the PRV variant TJ strain exhibited enhanced pathogenicity in pigs inoculated via intramuscular route. To develop an animal infection model for accurate evaluation of novel vaccines against the emergent PRV variant, we evaluated the pathogenicity of the PRV TJ strain of different doses in pigs infected via intranasal route. Groups (n = 5) of 7-week-old healthy pigs were inoculated intranasally with 10 3 , 10 4 , 10 5 , or 10 6 TCID 50 (median tissue culture infective dose) PRV TJ strain. Clinical signs, rectal temperature, virus shedding, pathological changes, and seroconversion were monitored. The results showed that the PRV TJ strain induced varied morbidity and mortality (0/5 to 5/5), clinical signs, and tissue lesions, increasingly correlated with the infection doses, and the median lethal dose (LD 50 ) of the virus was determined to be 10 4.5 TCID 50 . Together, this study demonstrates the dose-dependent pathogenicity of the PRV variant via the intranasal route of infection, which provides an ideal animal infection model for evaluation of novel vaccines against the emerging PRV variant.

Pseudorabies virus is transmitted among vaccinated conventional pigs, but not among vaccinated SPF pigs

Veterinary Microbiology, 2001

Whereas the reproduction ratio (R) of pseudorabies virus (PRV) in vaccinated speci®c pathogen free (SPF) pigs without maternally derived antibodies under experimental conditions has repeatedly been shown to be signi®cantly below 1, R in vaccinated conventional pigs in the ®eld with maternally derived antibodies was signi®cantly above 1. To exclude the difference in husbandry conditions as a cause for this discrepancy, we quanti®ed and compared the transmission of PRV in both groups under identical experimental conditions. Whereas none of the SPF sentinel pigs became infected (R 0, significantly < 1), all conventional sentinel pigs did become infected (R 2:5, significantly > 1). Moreover, only one SPF pigs shed virus in saliva, the mean cumulative titre being almost a 100-fold less than in conventional pigs (17 pigs, P 0:003). In addition, the mean proliferation of peripheral blood lymphocytes in response to PRV antigens was signi®cantly higher in SPF pigs than in conventional pigs at all points studied (P < 0:0001). Moreover, the virusneutralising antibody titre after vaccination was signi®cantly higher in SPF pigs than in conventional pigs. We conclude that the discrepancy in transmission between vaccinated SPF pigs and vaccinated conventional pigs cannot be attributed to the experimental conditions. #

Vaccination of pigs with a recombinant porcine adenovirus expressing the gD gene from pseudorabies virus

Vaccine, 2001

Five week old, commercially available large white pigs were vaccinated with either a single dose or two doses of a recombinant porcine adenovirus expressing the glycoprotein D gene from pseudorabies virus (PRV). Pigs were monitored for the development of serum neutralizing antibodies to PRV and challenged 3 weeks after final vaccination. Prior to challenge, pigs given 2 doses of the vaccine demonstrated boosted levels of antibody compared with those given a single dose, and all surviving pigs had increased neutralization titres over pre-challenge levels. Following challenge, pigs were monitored for clinical signs of disease, with blood and nasal swabs collected for virus isolation. All control animals became sick with elevated temperatures for 6 days post challenge, whereas; vaccinated animals displayed an increase in body temperature for only 2 -3 days. Control pigs and those given a single dose all lost condition, but the group given 2 doses remained healthy. At postmortem, gross lesions of pneumonia only occurred in control animals and those given a single dose of vaccine. Histology carried out on the brains of all animals demonstrated a difference in severity of infection and frequency of immunohistochemical antigen detection between test animals, with control and single dose groups being most severely affected and pigs given 2 doses the least. Virus isolation studies demonstrated that no viraemia could be detected, but virus was found in nasal swabs from some animals in both groups of vaccinates following challenge.

A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protect Pigs against a Virulent CSFV Challenge

Viruses

Classical swine fever (CSF) remains one of the most economically significant viral diseases affecting domestic pigs and wild boars worldwide. To develop a safe and effective vaccine against CSF, we have constructed a triple gene-deleted pseudorabies virus (PRVtmv)-vectored bivalent subunit vaccine against porcine circovirus type 2b (PCV2b) and CSFV (PRVtmv+). In this study, we determined the protective efficacy of the PRVtmv+ against virulent CSFV challenge in pigs. The results revealed that the sham-vaccinated control group pigs developed severe CSFV-specific clinical signs characterized by pyrexia and diarrhea, and became moribund on or before the seventh day post challenge (dpc). However, the PRVtmv+-vaccinated pigs survived until the day of euthanasia at 21 dpc. A few vaccinated pigs showed transient diarrhea but recovered within a day or two. One pig had a low-grade fever for a day but recovered. The sham-vaccinated control group pigs had a high level of viremia, severe lymphoc...

Cell biological and molecular characteristics of pseudorabies virus infections in cell cultures and in pigs with emphasis on the respiratory tract

Veterinary Research, 2007

In the present review, several cell biological and molecular aspects of virus-cell and virus-host (pig) interactions are reviewed for pseudorabies (Aujeszky's disease) virus. Concerning the virus-cell interactions, the complex cascade of events in the virus replication cycle is given together with the different mechanisms of cell-to-cell spread. The pathogenesis of pseudorabies virus infections in pigs is concentrated on the sequence of events in the respiratory tract. Finally, a short overview is given on the control of the disease and eradication of the virus by the combination of marker vaccines and discriminating ELISA. pseudorabies virus / virus replication / cell-associated spread / pathogenesis / control

Vaccination of pigs against pseudorabies with highly attenuated vaccinia (NYVAC) recombinant viruses

Veterinary Microbiology, 1993

Poxvirus reeombinants, based on the highly attenuated NYVAC strain of vacciula vires (Tartaglia et al., 1992), containing single gene inserts encoding the pseudorabies virus (PRV) giI, giII, or gp50 glycoproteins were tested for their immunogenicity in pigs. Twenty-four pigs were randomly divided into six groups of four. Groups 1-3 were inoculated with 107 CCID~o of NYVAC/PRV giI, NYVAC/ PRV gill, or NYVAC/PRV gp50, respectively, while groups 4 and 5 received the NYVAC parent virus or an inactivated PRV vaccine control, respectively. Group 6 represented the sham vaccinated control group. All inoculations were given by the intramuscular route on weeks 0 and 4. The candidate vaccines were shown to be safe with no local or systemic reactions. At 4 weeks following the second inoculation, all pigs were challenged by an oronasal administration of a virulent PRV strain. Pigs were monitored before and after challenge for clinical manifestations resulting from vaccination and challenge exposure, respectively. Sera were analyzed for PRV neutralizing activity. Virological analyses after challenge included assessment of virus shedding and the development of latent PRV infections. All but one animal developed latent PRV infection following challenge exposure; however, significant protection against PRV-induced signs was afforded by vaccination with either the NYVAC/PRV gp50 or NYVAC/PRV giI recombinant viruses, as well as with the inactivated PRV vaccine. The NYVAC/ PRV gp50 also reduced overall virus shedding after challenge. The extent of protection against PRVinduced clinical signs, in general, was associated with the level of pre-challenge virus neutralizing activity.

Protection of mice and swine from pseudorabies virus conferred by vaccinia virus-based recombinants

Journal of Virology, 1992

Glycoproteins gp50, gII, and gIII of pseudorabies virus (PRV) were expressed either individually or in combination by vaccinia virus recombinants. In vitro analysis by immunoprecipitation and immunofluorescence demonstrated the expression of a gII protein of approximately 120 kDa that was proteolytically processed to the gIIb (67- to 74-kDa) and gIIc (58-kDa) mature protein species similar to those observed in PRV-infected cells. Additionally, the proper expression of the 90-kDa gIII and 50-kDa gp50 was observed. All three of these PRV-derived glycoproteins were detectable on the surface of vaccinia virus-PRV recombinant-infected cells. In vivo, mice were protected against a virulent PRV challenge after immunization with the PRV glycoprotein-expressing vaccinia virus recombinants. The coexpression of gII and gIII by a single vaccinia virus recombinant resulted in a significantly reduced vaccination dose required to protect mice against PRV challenge. Inoculation of piglets with the ...