Investigation
Pathogen-host interaction studies allow us to define
relevant mechanisms in the immune response to clear up the infection, as well as
viral strategies for avoiding the immune response. One of the mechanisms described by our group involves ADCC (Antibody-dependent cellular cytotoxicity) responses against cells infected by PPRV in sheep, with protein H as the main target. Furthermore, this protein interacts with TLR2 in monocytic cells, leading their activation. We are currently performing
transcriptomic studies of
ovine immune cells obtained throughout BTV infections to determine different possible
mechanisms involved in protection.
A different line of research focuses on the
identification and characterization of epitopes to include in new vaccines and diagnostic methods. We have described CD4+ and CD8+ epitopes in BTV NS1 and VP7 proteins, as well as PPRV F and H proteins.
The
ovine CD70 and OX40L
costimulatory molecules, belonging to the TNF superfamily, have been described for the first time. These proteins were cloned and expressed in human adenovirus vector system (Ad5), showing their role as immunomodulatory molecules in sheep. Vaccine trials using these molecules as adjuvants are being evaluated.
Among the mechanisms ruminant virus have developed to evade the immune response, research is being conducted on viral interference with the innate response. Thus, BTV NS3 protein role in
the response to type I interferon (IFN-I) has been described. NS3 directs the STAT2 factor to the lysosome for degradation. Moreover PPRV V, P and W proteins have shown to block the response to IFN-I.
Another
evasion mechanism of the immune response involves BTV-induced immunosuppression during infection in sheep, in which follicular dendritic cells are eliminated, resulting in B-cells lack of cell division. This causes a delay in the production of high affinity antibodies, allowing the systemic expansion of the virus.
By using the
Ad5-based vaccines platform -an excellent vector given the high immunogenicity induced in the absence of adjuvants, and their safety- we created H- and F-expressing proteins vaccines against PPRV, which
induced protection in sheep. Likewise, multivalent vaccines capable of protecting against
several BTV serotypes are being generated.
The
vaccine platform based on calicivirus-derived chimeric
VLPs includes foreign immunogenic epitopes. RHDV VLPs are excellent vaccine vectors, capable of inducing a specific protective immune response against both T and B epitopes. Such capacity has been demonstrated with VLPs that incorporate epitopes from different pathogens, such as feline calicivirus, influenza virus or the yellow fever virus (YFV). Bioengineered VLPs have been developed, with
higher yields and their
physical stability increased, reducing production costs, as well as increasing their lifetime period and VLPs-based vaccines immunogenicity.
Dendrimeric peptide vaccines design allows the multimeric presentation of epitopes in synthetic branched structures that constitute very safe and efficient vaccines. Using YFV as a model, dendrimers were designed, capable of inducing a specific immune response and protection against various YFV serotypes in
pigs by using a
single vaccine dose. This allows reducing costs and their use as an emergency vaccine. We have designed dendrimers capable of inducing immune response and
protection in bovines in collaboration with researchers from Argentina (INTA-CONICET).
We have also developed
diagnostic tests to be complementary with DIVA vaccines, for adequate epidemiological monitoring of vaccinated and infected animals.
Non-infectious diagnostic
reagents have been generated (recombinant proteins, VLPs, peptides, and monoclonal antibodies). Serological tests with the ability to distinguish between
RHDV variants were also developed, among others.
Recently, our group started several projects for the approach of antivirals against
SARS-Cov2 virus, new vaccines evaluations with animal models and the development of vaccines based on dendrimeric peptides presentign B and T epitopes, as well as vaccines based on RHDV chimeric VLPs presenting protein S antigenic sites.
