Immunopathogenesis of HIV Infecion and HIV vaccine development
The purpose of this programme of work will be the development of new immunogens against HIV infection, investigation their interactions with myeloid dendritic cells and to assessment of their effectiveness of such immunogens to induce HIV-specific immune responses. In addition, development of immunogens able to elicit a broadly neutralizing antibodies activity.
Most common techniques used:
- Viral cultures in human PBMCs and human cell lines.
- Cell cultures both in human and murine cells.
- Molecular biology (PCR, real-time PCR, cloning and sequencing)
- Immune responses evaluation: i) Cellular immune responses: Detection of pro-inflammatory cytokines, Elispot, Proliferative capacity, Flow cytometry panels for studying memory T cells and Virus Inhibition Replication assays. ii) Humoral immune responses: Determination of systemic IgG or IgA responses against HIV by ELISA and Neutralization assays.
Relevant recent publications:
- A therapeutic dendritic cell-based vaccine for HIV-1 infection. J. Infect. Dis. 203:473-478 (2011).
- Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02). Vaccine 29:8309-8316 (2011).
- Phenotypic and functional characteristics of HIV-specific CD8 T cells and gag sequence variability after autologous dendritic cells based therapeutic vaccine. Vaccine 27:6166-6178 (2009).
- Broadly cross-neutralizing antibodies in HIV-1 patients with undetectable viremia. J. Virol. 85:5804-5813 (2011).
The group has been involved in the HIV/AIDS research since the very beginning (1981) and has contributed to the field with relevant new information. We have proved the concepts that 1) a therapeutic vaccine (based on autologous dendritic cells) may be feasible; 2) of an MVA-B vector as a candidate for a preventive vaccine in human healthy volunteers and 3) the identification of broadly neutralizing antibodies in HIV-1 chronic infected patients both untreated and on antiretroviral treatment.
In 2006, Dr Gatell, created a research program on preventive and therapeutic vaccines (HIVACAT). The members of the group are authors of more than 900 international papers cited more than 20.000 times with an impact factor of more than 2000 points in the last 10 years, about AIDS.
HIV, immunopathogenesis, cellular immune response, humoral response, therapeutic vaccines, preventive vaccines.
The candidate will join to one of the research line within our group and the desirable achievements and outcomes in the candidate research will depend on the research line chosen including development of new immunogens against HIV infection, investigation of pre-clinical immunogens interaction with myeloid dendritic cells, effectiveness assessment of such immunogens inducing HIV-specific immune responses. In addition, the development of immunogens able to elicit a broadly neutralizing antibodies activity.
The candidate should develop a thorough understanding of the research field and be involved in the intellectual decision making process required for successful completion of the project, contribute to the design and planning of experiments in relation to this project and publish his results in scientific international journals.
Team strategic objective in IDIBAPS
In the HIV/AIDS field:
- Natural and adquired defense mechanisms against HIV infection including development of therapeutic and preventive vaccines.
- Efficacy, tolerance and resistance to new antiretrovirals.
- Immunopathogenesis, treatment responses and resistance mechanisms to some opportunistic infections such as tuberculosis, PCP and toxoplasmosis.