To achieve this, we analyse basic aspects of the antiviral cellular immune response and vaccination. We used mouse models with partial immunodeficiency, combined with infection with two viruses relevant for vaccine development. Additionally, we are exploring new technological platforms that facilitate cellular response by transporting antigens to the appropriate cellular compartments for processing.
As an experimental model, we used mice deficient in the transporter associated with antigenic processing (TAP). This transporter plays a central role in the antigen presentation pathway through MHC class I molecules (MHC-I), which are recognized by pathogen-specific cytotoxic CD8+ T lymphocytes. These lymphocytes mediate the elimination of infected cells in vivo.
TAP is frequently inactivated in metastases and is also the target of viruses. In both cases, this results in evasion of detection and clearance by CD8+ T cells.
In our laboratory, we are identifying viral peptide epitopes that are presented by MHC-I in the absence of TAP. We also investigated the proteases and antigenic processing pathways that generate these epitopes in infected cells. Furthermore, we evaluated their contribution to the CD8+ response in these animals.
The viral infection models we use are vaccinia virus and mouse cytomegalovirus. The vaccinia virus, a poxvirus like mpox, is the vaccine vector of the first and greatest success in the use of vaccination in public health: the eradication of smallpox, officially declared in 1980. Cytomegaloviruses are relevant as potential vaccine vectors, since during latent infection they present viral antigens continuously, without associated pathology, leading throughout life to a high number of virus-specific T lymphocytes, the so-called inflationary memory.
Finally, in our continuing study of the immune response to poxviruses, we are exploring how this information can be applied to new emerging diseases. One of the most recent examples is the monkeypox (Mpox) outbreak. In particular, we are looking at the protective immune response in the elderly who received smallpox vaccinations more than fifty years ago, and their ability to respond to new viral threats.