ABSTRACT
Bovine viral diarrhea virus (BVDV) is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2) was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5Ag of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle
El virus de la diarrea viral bovina (BVDV) es causante de importantes pérdidas económicas a nivel mundial. La proteína E2 es la inmunodominante del virus y es la candidata para desarrollar vacunas de subunidad. Para mejorar su inmunogenicidad, una versión truncada de la E2 (tE2) se fusionó a un anticuerpo de cadena simple (APCH), que se dirige a las células presentadoras de antígeno. Se expresaron las proteínas APCH-tE2 y tE2 en el sistema de baculovirus y su inmunogenicidad fue evaluada y comparada en cobayos; la proteína APCH-tE2 fue la que indujo la mejor respuesta humoral. Por dicha razón se la evaluó en bovinos utilizando 1,5µg de antígeno. Los animales presentaron altos títulos de anticuerpos neutralizantes contra BVDV hasta un año posinmunización. Esta nueva vacuna está en proceso de escalado y se transfirió al sector privado. Actualmente se está evaluando para su registro como la primera vacuna argentina de subunidad para bovinos
Subject(s)
Animals , Cattle , Guinea Pigs , Diarrhea Viruses, Bovine Viral/immunology , Vaccines, Subunit/biosynthesis , Antigen-Presenting Cells/drug effects , Baculoviridae/immunology , Immunization/veterinary , Adenovirus E2 Proteins/immunology , Diarrhea Viruses, Bovine Viral/drug effects , Antibodies, Neutralizing/analysisABSTRACT
We have previously evaluated a Semliki Forest virus (SFV) replicon vectored DNA vaccine (pSFV1CS2-E2) and a recombinant adenovirus (rAdV-E2) expressing the E2 glycoprotein of classical swine fever virus (CSFV) in pigs. The results showed that the immunized pigs were protected from virulent challenge, but few pigs showed short-term fever and occasional pathological changes following virulent challenge. To enhance the immunogenecity of the vaccines, we tried a prime-boost vaccination strategy using a combination of prime with pSFV1CS2-E2 followed by boost with rAdV-E2. The results showed that all the immunized pigs developed high-level CSFV-specific antibodies following prime-boost immunization. When challenged with virulent CSFV, the immunized pigs (n = 5) from the heterologous boost group showed no clinical symptoms, and CSFV RNA was not detected following challenge, whereas one of five pigs from the homologous boost group developed short-term fever and CSFV RNA was detected. This demonstrates that the heterologous prime-boost vaccination regime has the potential to prevent against virulent challenge.