Description

Besides its importance as a zoonotic agent, Swine Influenza Virus (SwIV) is also important for its impact in the pig farming industry. Swine influenza is a relevant porcine respiratory disease, whose importance has been often underestimated due to the impact of other respiratory pathologies. Our data in collaboration with HIPRA S.A. have shown by phylogenetic analysis that circulating SIV strains in Spain belonged to the lineages “Avian-Like” H1N1, “Human-Like” H3N2, and “Human-Like” H1N2, showing tight relationships with early or contemporary strains described in Europe. Also, our results indicated that reassortment events could have influenced the evolution, indicating that circulating SIV strains in pig farms could be a potential zoonotic agent. Thus, control of SwIV is very important not only to prevent pulmonary lesions in pigs but also to control a zoonotic infection.

ASFV causes severe disease of domestic pigs that can result in up to 100% mortality with concomitant serious socio-economic impacts. Nowadays, there is no vaccine against ASFV. Historically, vaccine development has been brought about by an essentially empirical approach where antibodies were usually the major protective factor. However, there are numerous pathogens for which this approach has not proved protective, including ASFV, for which the reasons remain unclear. Thus, other vaccination approaches are required, which can only be informed by a deeper knowledge of immune responses during host-pathogen interactions. The work in the group is directed into a better understanding of the immune responses required for protection in order to provide the information for rationally design a vaccine against ASFV or SwIV.

A major drawback in vaccine development in animal health is the fact that antigenic peptides presented by MHC class I (in pigs SLA-I) have not been fully characterized, hampering the rational design of vaccines. Identification and characterization of B- and T-cell epitopes (also known as antigens) for a given pathogen has proved crucial for understanding the basic mechanisms of immunological protection and for the rational design of effective vaccines. Protective immunity is usually mediated by B lymphocytes, CD8+/CD4+ T lymphocytes or both. Recognition of epitopes by lymphocytes from different species and individuals is restricted by the major histocompatibility complex (MHC) molecules – named swine leukocyte antigen (SLA) in pigs- which is responsible for foreign antigen presentation. In the case of viral infections, classical SLA class I (SLA-I) molecules act as molecular cradles that present endogenous and foreign peptides or epitopes to cytotoxic CD8+T cells (CTL) at the cell surface of healthy and infected cells. Thus, they provide the immune system with a mechanism for interrogating the viral proteome from the outside of infected cells.

Our team and in collaboration with other international groups have applied reverse vaccinology to identify cross-reacting MHC class I T-cell epitopes from two different Swine Influenza virus (SwIV) H1N1 lineages in pigs presented by SLA-1*0702. The majority of the identified T-cell epitopes were conserved between the examined lineages, particularly the newly defined epitope in NA171-180 (Figure 1).  In a further work, we studied two other SLA-I molecules (SLA-1*14:02 and SLA-2*11:04) by their crystal structure. Our studies revealed their anchor residues as well as new swine influenza epitopes (Figure 2). In summary, we have already identified several antigenic peptides from influenza virus in three SLA-I. Our future work will extend our previous results to other viruses and other SLA-I.