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

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 viru

Field Evaluation Of Safety During Gestation And Horizontal Spread Of A Recombinant Differential Bovine Herpesvirus 1 (bohv-1) Vaccine

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 107.4 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 (107.6TCID50) 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.2515458Belknap, E.B., Walters, L.M., Kelling, C., Ayers, V.K., Norris, J., McMillend, J., Hayhowe, C., Collins, J.K., Immunogenicity and protective efficacy of a gE, gG and US2 gene-deleted bovine herpesvirus-1 (BHV-1) vaccine (1999) Vaccine, 17, pp. 2297-2305Bouma, A., De Jong, M.C.M., Kimman, T.G., Transmission of pseudorabies virus within pig populations is independent of the size of the population (1995) Prev. Vet. Med., 23, pp. 163-172Casal, J., Planasdemunt, L., Varo, J.A., Martín, M., The use of different vaccination schedules for sows to protect piglets against Aujeszky's disease (2004) Vet. Med. B, 51, pp. 8-11D'Arce, R.C.F., Almeida, R.S., Silva, T.C., Franco, A.C., Spilki, F., Roehe, P.M., Arns, C.W., Restriction endonuclease and monoclonal antibody characterization of Brazilian isolates of bovine herpesviruses types 1 and 5 (2002) Vet. Microbiol., 88, pp. 315-324Ellis, J.A., Hassard, L.E., Cortese, V.S., Morley, P.S., Effects of perinatal vaccination on humoral and cellular immune responses in dams and young calves (1996) J. Am. Vet. Med. Assoc., 208, pp. 393-400Flores, E.F., Donis, R.O., Isolation of a mutant MDBK cell line resistant to bovine viral diarrhea virus infection due to a block in viral entry (1995) Virology, 208, pp. 565-575Flores, E.F., Osorio, F.A., Zanella, E.L., Kit, S., Kit, M., Efficacy of a deletion mutant bovine herpesvirus-1 (BHV-1) vaccine that allows serologic differentiation of vaccinated from naturally infected animals (1993) J. Vet. Diagn. Invest., 5, pp. 534-540Franco, A.C., Rijsewijk, F.A.M., Flores, E.F., Weiblen, R., Roehe, P.M., Construction and characterization of a glycoprotein E deletion of bovine herpesvirus type 1.2 strain isolated in Brazil (2002) Braz. J. Microbiol., 33, pp. 274-278Franco, A.C., Spilki, F.R., Esteves, P.A., Lima, M., Weiblen, R., Flores, E.F., Rijsewijk, F.A.M., Roehe, P.M., 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 (2002) Pesq. Vet. Bras., 22, pp. 135-140Hage, J.J., Schukken, Y.H., Barkema, H.W., Benedictus, G., Rijsewijk, F.A.M., Wentink, G.H., Population dynamics of bovine herpesvirus infection a dairy herd (1996) Vet. Microbiol., 53, pp. 169-180Guy, J.S., Potgieter, L.N., Bovine herpesvirus-1 infection of cattle: Kinetics of antibody formation after intranasal exposure and abortion induced by the virus (1985) Am. J. Vet. Res., 46, pp. 893-898Kaashoek, M., (1995) Marker Vaccines Against Bovine Herpesvirus 1 Infections, 155p. , Ph.D. Thesis, Utrecht University, NetherlandsKleiboeker, S.B., Lee, S.M., Jones, C.A., Estes, D.M., Evaluation of shedding of bovine herpesvirus 1, bovine viral diarrhea virus 1, and bovine viral diarrhea virus 2 after vaccination of calves with a multivalent modified-live virus vaccine (2003) J. Am. Vet. Med Assoc., 222, pp. 1399-1403Lomba, F., Vascoboinic, E., Zygraich, N., Immunization of pregnant dams with a temperature-sensitive mutant of the IBR Virus (1976) 6th Int. Congr. Diseases of Cattle, pp. 395-399. , ParisMars, M.H., De Jong, M.C.M., Van Oirschot, J.T., A gE-negative BHV-1 vaccine virus strain cannot perpetuate in cattle populations (2000) Vaccine, 18, pp. 2120-2124McFelly, R.A., Merrit, A.M., Stearly, E.L., Abortion in a dairy herd vaccinated for infectious bovine rhinotracheitis (1964) Vet. Path., 1, pp. 7-17Miller, J.M., Whetstone, C.A., Van Der Maaten, M.J., Abortfacient property of bovine herpesvirus type 1 isolates that represent three subtypes determined by restriction endonuclease analysis of viral DNA (1991) Am. J. Vet. Res., 52, pp. 458-461Miller, J.M., Whetstone, C.A., Bello, L.J., Lawrence, W.C., Whitbeck, J.C., Abortions in heifers inoculated with a thymidine kinase-negative recombinant of bovine herpesvirus 1 (1995) Am. J. Vet. Res., 56, pp. 870-874Mitchell, D., An outbreak of abortion in a dairy herd following inoculation with an intramuscular infectious bovine rhinotracheitis virus (1964) Can. Vet. J., 26, pp. 8-14Odde, K.G., Survival of the neonatal calf. Factors influencing colostral and calf serum immunoglobulin levels (1988) Vet. Clin. North Am. Food Anim. Pract., 4, pp. 501-508Pastoret, P.P., Babiuk, L.A., Misra, V., Griebel, P., Reactivation of temperature sensitive and non-temperature-sensitive infectious bovine rhinotracheitis vaccine virus with dexamethasone (1980) Infect. Immun., 29, pp. 483-488Roehe, P.M., (1991) Studies on the Comparative Virology of Pestiviruses, 361p. , Ph.D. thesis. University of Surrey, Guildford, UKSiebert, S., Auer, S., Heinem, E., Kretzdom, D., Strube, W., Marker vaccines - Opportunities for IBR control. Part I: BHV-1 infections - The problem (1995) Tierärztl. Umschau, 50, pp. 530-533Siebert, S., Auer, S., Heinem, E., Kretzdom, D., Strube, W., Marker vaccines - Opportunities for IBR control. Part II: Safety and efficacy of the gE-deleted Bayovac IBR marker vaccines (1995) Tierärztl. Umschau, 50, pp. 582-584Strube, W., Abar, B., Bergle, R.D., Safety aspects in the development of an infectious bovine rhinotracheitis marker vaccine. Non-target effects of live vaccines (1995) Dev. Biol. Stand., 84, pp. 75-81Turin, L., Russo, S., Poli, G., BHV-1: New molecular approaches to control a common and widespread infection (1999) Mol. Med., 5, pp. 261-284Van Drunen Littel-van Den Hurk, S., Parker, M.D., Massie, B., Van Den Hurk, J.V., Harland, R., Babiuk, L.A., Zamb, T.J., Protection of cattle from BHV-1 infection by immunization with recombinant glycoprotein gIV (1993) Vaccine, 11, pp. 25-35Van Engelenburg, F.A.C., Kaashoek, M.J., Van Oirschot, J.T., Rijsewijk, F.A.M., A glycoprotein E deletion mutant of bovine herpesvirus 1 infects the same limited number of tissues in calves as wild-type virus, but for a shorter period (1995) J. Gen. Virol., 76, pp. 2387-2392Wentink, G.H., Van Oirschot, J.T., Verhoeff, J., Risk of infection with bovine herpes virus 1 (BHV-1): A review (1993) Vet. Quarterly, 15, pp. 30-33Whetstone, C.A., Wheeler, J.G., Reed, D.E., Investigation of possible vaccine-induced epizootics of infectious bovine rhinotracheitis, using restriction endonuclease analysis of viral DNA (1986) Am. J. Vet. Res., 47, pp. 1789-1795Zuckermann, F.A., Husmann, R.J., Schwartz, R., Brandt, J., Mateu De Antonio, E., Martin, S., Interleukin-12 enhances the virus-specific interferon gamma response of pigs to an inactivated pseudorabies virus vaccine (1998) Vet. Immunol. Immunopath., 63, pp. 57-6

Switching between TNFα antagonists in rheumatoid arthritis: personal experience and review of the literature

The treatment of rheumatoid arthritis (RA) has evolved over the past decade with the introduction of anti-tumor necrosis factor (TNF) α agents, which allowed remarkable advances in controlling signs and symptoms of inflammation and in slowing joint destruction (1-3). However, some patients do not respond or show suboptimal response to the currently available anti- TNFα agents (infliximab, etanercept, and adalimumab) used either as monotherapy or in combination with methotrexate. Furthermore, patients who respond initially may lose efficacy over time (4) or develop adverse events

Matrix elements relevant for Delta I=1/2 rule and epsilon-prime from Lattice QCD with staggered fermions

We perform a study of matrix elements relevant for the Delta I=1/2 rule and the direct CP-violation parameter epsilon-prime from first principles by computer simulation in Lattice QCD. We use staggered (Kogut-Susskind) fermions, and employ the chiral perturbation theory method for studying K to 2 Pi decays. Having obtained a reasonable statistical accuracy, we observe an enhancement of the Delta I=1/2 amplitude, consistent with experiment within our large systematic errors. Finite volume and quenching effects have been studied and were found small compared to noise. The estimates of epsilon-prime are hindered by large uncertainties associated with operator matching. In this paper we explain the simulation method, present the results and address the systematic uncertainties.Comment: 40 pages, 17 figures, LATEX with epsf, to be submitted to Phys. Rev. D. Minor errors are corrected, some wording and notation change

On the freezing of variables in random constraint satisfaction problems

The set of solutions of random constraint satisfaction problems (zero energy groundstates of mean-field diluted spin glasses) undergoes several structural phase transitions as the amount of constraints is increased. This set first breaks down into a large number of well separated clusters. At the freezing transition, which is in general distinct from the clustering one, some variables (spins) take the same value in all solutions of a given cluster. In this paper we study the critical behavior around the freezing transition, which appears in the unfrozen phase as the divergence of the sizes of the rearrangements induced in response to the modification of a variable. The formalism is developed on generic constraint satisfaction problems and applied in particular to the random satisfiability of boolean formulas and to the coloring of random graphs. The computation is first performed in random tree ensembles, for which we underline a connection with percolation models and with the reconstruction problem of information theory. The validity of these results for the original random ensembles is then discussed in the framework of the cavity method.Comment: 32 pages, 7 figure

Antigenic and molecular characterization of eight samples of Aujeszky's disease virus isolated in the state of Rio Grande do Sul, Brazil, in 2003

Pseudorabies or Aujeszky's disease (AD), caused by pseudorabies virus (PRV) is a major concern in swine production. In the state of Rio Grande do Sul, Brazil, AD was only detected in 1954, in cattle. In 2003 two outbreaks of encephalitis occurred on the northern region of the state, close to the border with the state of Santa Catarina. Pseudorabies virus (PRV) was isolated from distinct farms within the region and subjected to antigenic and genomic analyses. These isolates were compared with prototype strains NIA-3 and NP. Antigenic characterization with a panel of monoclonal antibodies (Mabs) directed to viral glycoproteins (gB, gC, gD and gE-,) was performed by an imunoperoxidase monolayer assay (IPMA) on infected cell monolayers. Genomic characterization was carried out by restriction enzyme analysis (REA) of the whole DNA viral genome with Bam HI. The antigenic profile of the eight isolates from Rio Grande do Sul as well as strains NIA-3 and NP were similar. REA analysis revealed that all isolates from Rio Grande do Sul displayed a genomic type II arrangement, a genotype often found in other outbreaks of AD previously reported in other Brazilian states. The results obtained suggest that the eight isolates examined here were similar