Tesis de la Gordilla
Bovine Viral Diarrhea Virus (BVDV) belongs to the genus Pestivirus, in the family Flaviviridae. BVDV is distributed worldwide and causes important economical losses to cattle and biological industries. BVDV infection results in clinical manifestations in cattle that range from mild respiratory or ga...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | |
| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
| Publicado: |
Universidad de Buenos Aires. Facultad de Ciencias Veterinarias
2017
|
| Materias: | |
| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=avaposgra&cl=CL1&d=HWA_7065 https://repositoriouba.sisbi.uba.ar/gsdl/collect/avaposgra/index/assoc/HWA_7065.dir/7065.PDF |
| Aporte de: |
| Sumario: | Bovine Viral Diarrhea Virus (BVDV) belongs to the genus Pestivirus, in the family Flaviviridae. BVDV is distributed worldwide and causes important economical losses to cattle and biological industries. BVDV infection results in clinical manifestations in cattle that range from mild respiratory or gastroenteric disease to hemorrhagic syndromes and mucosal disease, depending on the virulence of the virus and the reproductive and immune status of\nthe host. The strategy to control BVDV in Argentina is based on vaccination with inactivated formulations. However, these commercial vaccines are not useful enough to protect cattle\nfrom BVDV. Given the need for updated information about circulating strains of BVDV in Argentina, it was proposed to study the phylogenetic and antigenic characteristics of 30\nrecently isolated strains obtained from ?Pampa Húmeda? region; and with that information, to develop a subunit vaccine based on a truncated form of BVDV E2 glycoprotein (tE2), expressed in Baculovirus Expression Vector System.\nIt is well-known that subunit vaccines generally evoke poor immunity so repeated and high doses of antigen are required to induce an appropriate immune response. In order to enhance the immunogenicity of tE2 glycoprotein, and to reduce the amount of antigen, it was proposed to use the single chain antibody ?APCH? to target tE2 protein to antigen\npresenting cells.\nResults from this work show the presence of three BVDV subgenotypes in the studied region and an important antigenic diversity among them, which is of great importance for the development of vaccines and diagnostic kits for BVDV. In regard to the vaccine development, it was possible to generate oily formulations based on tE2 glycoprotein and on APCH-tE2 fusion protein from Singer strain (BVDV 1a). Both immunogens were evaluated and compared in Guinea Pig model and even though both vaccines induced neutralizing antibodies, tE2 protein targeted by APCH was more efficient: evoked a higher humoral response by using a lower dose. Based on this result, the fusion protein was evaluated in adult cattle; and was able to induce high levels of neutralizing antibodies (>128) up to 360 days post vaccination. Due to this great performance, at this\nmoment the vaccine development is in SENASA register stage. With the intention of developing a vaccine capable of providing protection against\nthe three genotypes of BVDV, it was generated a combined vaccine based on tE2 proteins from BVDV1a (Singer), BVDV 1b (25366) and BVDV 2a (VS253), which are antigenically 23 different strains, fused to APCH. This combined vaccine was first evaluated in guinea pigs, which developed neutralizing antibodies against the three viral strains. Lastly, the combined vaccine was used to perform a challenge assay in colostrums-deprived calves with heterologous BVDV 1b and BVDV 2 field strains. Vaccinated animals showed elimination or\nreduction of pyrexia, nasal and ocular virus shedding, viremia, leukopenia and clinical signs of BVDV in comparison with non-vaccinated control animals |
|---|