Specific CD8+ T cell repertoire in HIV long-term non-progressors

Referenznummer TO 01-00748

The Challenge
The mechanisms underlying non-progression in HIV-1 infection are not well understood. CD8+ T cell responses are thought to be crucial for controlling or limiting HIV-1 replication by direct elimination of infected cells and secretion of a number of soluble factors, but ultimately fail to control virus replication in most infected persons. Consequently, durable control of HIV-1 replication and disease is achieved by administration of combination antiretroviral therapy (ART). Long-term non-progressors (LTNP) represent a minority of HIV-1 infected individuals able to achieve long-term control of HIV-1 replication without the administration of ART. The analysis of the immune response in LTNP may help to uncover possible mechanisms and correlate of protection from HIV-1 disease. The identification of immunological correlates of protection will be key for the development of a vaccine against HIV.

Technology

To elucidate the role of CD8+ T-cells in the control of HIV-1 infection, HIV-1-specific CD8+ T cell responses in a cohort of LTNP in comparison to late-progressors (LP) and chronic infected HIV individuals (CHI) were studied. The inventors optimized a method of peptide designing, called Variable Overlapping Peptide Scanning Design (VOPSD). The new peptides have been shown to be superior in detecting CD8+ T-cell responses without loosing the ability to uncover CD4+ T-helper responses. The combination of the VOPSD peptides together with an ad hoc developed protocol of multiparametric flow-cytometry lead to the identification of the MIP-1β+ IFN-γ-CD45RA+ CD8+ T cell population almost exclusively present in LNTP.

Commercial Benefit and Opportunity

The present invention discloses a novel CD8+ T cell population exclusively present in HIV-1 infected individuals with a non-progressive course of the disease. MIRA represents a potential marker to identify those individuals able to control or limit HIV-1 replication. Detection of the MIRA T cell population will allow the testing of candidate HIV-1 vaccines for the capacity to elicit efficacious anti-HIV-1 immune responses and to ameliorate the timing of ART in HIV-infected individuals. Evaluation of MIRA can be easily done by FACS analysis.
The technology is available for (non)-exclusive licensing. Parties interested in collaborative research and development are highly welcomed.

Developmental Status
A preliminary longitudinal study demonstrated the stability of the MIRA CD8 T cells in LTNP over the time. Ongoing experiments are performed to better characterize the new population regarding additional functions and mechanism of action.

Patent Situation
An EP and PCT application have been filed.

Relevant Publication

Kutscher et al. (2008), AIDS Res. Therapy 5:22