Investigation
Animal Health as well as to establish animal infection models and virus detection tools. Our work has focused mainly on Rift Valley fever virus (RVFV) and bluetongue virus (BTV). Other arboviruses of interest are Crimean-Congo hemorraghic virus (CCHFV), Schmallenberg virus (SBV) and African Horse sickness virus (AHSV). The group maintains a clear vocation for national and international collaborations in efforts to develop novel safer and efficacious control strategies for these viral diseases.
Regarding BTV, we have described that the NS1 protein expressed by a modified vaccinia Ankara virus (MVA) vector can provide multiserotype protection against BTV, which is largely dependent on CD8 T cell responses. We have also engineered recombinant vaccine candidates based on proteins VP2, VP7, and NS1 of BTV-4 or VP2 and NS1 of AHSV-4 that were incorporated into avian reovirus muNS-Mi microspheres or rMVA. The combination of these two antigen delivery systems protected IFNAR (-/-) mice against lethal challenges with homologous and heterologous serotypes of BTV and AHSV.
With respect to RVFV we have shown that treatment with silver nanoparticles greatly reduced the infectivity of RVFV. Regarding vaccine strategies, we tested the ability of homologous and heterologous DNA and MVA prime boost vaccination to induce and sustain immune responses in sheep. Furthermore, a bivalent MVA vaccine expressing BTV-NS1 and RVFV-GnGc induced protection against both virus infections in mice and reduced BTV and RVFV viremia in sheep. Also, using reverse-genetics approaches, we have generated a recombinant RVFV vector encoding BTV-VP2 or BTV-NS1 antigens. The protection efficacy and immunogenicity of these vectors have been tested in several animal models. Finally, after serial passages in the presence of mutagenic drugs, we have selected a hyperattenuated variant of RVFV, and identified point mutations that reduce virulence in vivo but maintain RVFV immunogenicity. All these data, have allowed us to optimize the development of RVFV as a vaccine vector for other ruminant pathogens, allowing, for example, the expression of antigens from Neospora caninum or the Peste-des-petits-ruminants virus (PPRV).
Regarding CCHF, we have cloned and expressed CCHFV antigens in several expression systems (bacterial, insect and mammalian) for use in diagnostic and monoclonal antibody (mAb) production. In addition, in collaboration with the Department of Biotechnology, we have generated rMVAs expressing CCHF antigens to be used as potential vaccines.
Influenza A viruses (IAV) are pathogens of great significance to public and animal health, causing an enormous economic impact. The laboratory uses a wide range of in vitro and in vivo approaches to better understand IAV biology, the viral factors involved in pathogenesis or host adaptation, and the development of new vaccines and antivirals to prevent or treat IAV infections. We are studying the role and regulation of viral proteins associated with pathogenesis or involved in the modulation of the immune response, such as NS1, PA-X, PB1-F2 or the replication complex components. The knowledge obtained from our research would allow the rational design of new and improved vaccines, as well as for the identification of potential antivirals targeting specific viral functions and/or viral components, for the treatment of influenza viral infections
The explosive emergence of SARS-CoV-2 infection in humans has resulted in a pandemic of coronavirus disease 2019 (COVID-19) with an alarming case fatality posing a threat to human health and socioeconomic activities across the world of an unprecedented magnitude since the “Spanish flu” pandemic in 1918/1919. Our current research focuses on the development of potential vaccines able to induce robust humoral and cellular responses to prevent SARS-CoV-2 infections, and the discovery of antivirals and new technologies to combat the virus propagation.
