Further Developments of New Immunogenic Peptide-based HIV Vaccines Targeting Dendritic Cells

Therapeutic HIV vaccines targeting dendritic cells have so far shown more promising results than preventive HIV vaccines and may become an alternative even for prophylaxis. This Proposal describes plans for basic clinical studies on further characterizati on and developments of new immunization strategies for peptide-based therapeutic HIV vaccines. These peptides have already proven to induce new, strong and lasting cellular immune responses in HIV-infected patients, responses which were associated with im proved control of viral replication and delayed resumption of antiretroviral treatment. This application focus on explorative and novel innovative aspects of peptide immunization against HIV and will address a number of key questions in HIV vaccinology to better understand and improve HIV vaccines. A newly established Translational HIV Research Platform will facilitate subprojects and is supportewd by the NRC under the Global Health Program. By joining complementary expertise by our groups in chemistr y, clinical immunology, vaccinology, adjuvant technology, immune modulation and cellular signalling, further basic clinical research of the immunogenic HIV peptides will be coordinated. The proposal will provide explorative data on use and administration of the peptide vaccines which can be directly exploited in future clinical trials: - Follow-up of already immunized patients, exploring durability of vaccine-induced HIV-specific responses and relation to clinical benefit, development of resistance and e ffects of additional boosting - Exploring basic key questions in HIV vaccinology, such as immune escape, tolerance in terms of regulatory T cells, best surrogate markers for vaccine-induced responses as well as impact of immunopathological mechanisms in HIV, such as persistent immune activation and disturbances in T cell signalling - Pilot studies exploring factors that might optimize boosting as well as alternative adjuvants and application strategies.