Understanding the biology of dendritic cells (DC) in HIV infection and their role as initiators of HIV-specific adaptive immune response is crucial to understanding the mechanisms involved in susceptibility/resistance and HIV disease progression. In addition, the functional complexity of the HIV-specific immune response and the lack of a unique and reliable correlate of protection against infection or disease progression constitute serious obstacles to the development of an effective vaccine. Today there is strong evidence to support the hypothesis that dendritic cells play an important role in orchestrating an efficient and sustained immune response against HIV-1, whether helper (CD4 or Th) or cytotoxic (CD8 or CTL) T cells to enable control of viral replication. Therefore, improving and optimizing this heterogeneous response is a fundamental objective for controlling infection and improving new preventive and therapeutic vaccines.

In this context, we have shown that adenosine desaminase (ADA) and alpha-defensins play an important role in dendritic cells, improving HIV-specific T cell immune responses and being potential adjuvants to HIV vaccines. All this knowledge has been the starting point for the design of a several vaccines against HIV, such as vaccines based on: MVA-B vectors, mRNA or HIV-1 inactivated loaded dendritic cells against HIV that were analyzed in our laboratory at the Hospital Clínic de Barcelona/IDIBAPS. The T cell immune responses to the candidate vaccines were evaluated in Clinical trials and monitored by ELISPOT technique and by flow cytometry immune phenotype. The latest Phase II clinical trial that we participated was a vaccine composed by HIV autologous heat inactivated  dendritic cells previously patented by our research group and produced under GMP conditions in a clean room (CREATIO).

We have recently found that cytotoxic T cells and NK cell populations developed during treatment with drugs against chronic myeloid leukemia, such as Dasatinib, protect autologous CD4+ T cells from HIV-1 infection, activating a potent immune response, not only against cancer cells, but also viruses-infected cells.

Understanding the biology of dendritic cells (DC) in HIV infection and their role as initiators of HIV-specific adaptive immune response is crucial to understanding the mechanisms involved in susceptibility/resistance and HIV disease progression. In addition, the functional complexity of the HIV-specific immune response and the lack of a unique and reliable correlate of protection against infection or disease progression constitute serious obstacles to the development of an effective vaccine. Today there is strong evidence to support the hypothesis that dendritic cells play an important role in orchestrating an efficient and sustained immune response against HIV-1, whether helper (CD4 or Th) or cytotoxic (CD8 or CTL) or B-lymphocytes to enable control of viral replication. Therefore, improving and optimizing this heterogeneous response is a fundamental objective for controlling infection and improving new preventive and therapeutic HIV vaccines. In this context, we have shown that adenosine desaminase (ADA) and alpha-defensins play an important role in dendritic cells, improving HIV-specific immune responses and being potential adjuvants to HIV vaccines. All this knowledge has been the starting point for the design of a cellular vaccine based on dendritic cells against HIV that we are currently carrying out at the Hospital Clínic de Barcelona/IDIBAPS/CREATIO. The response to this vaccine is monitored by ELISPOT technique and by flow cytometry of lymphocyte populations. With this vaccine we are conducting a Phase II clinical trial producing both HIV and autologous dendritics under GMP conditions in a clean room (CREATIO) validated with our dendritic cell production procedure previously patented by our own research group.