The AELIX Therapeutics HIV vaccine programme is based on an innovative T-cell vaccine immunogen design that directs the body’s immune defence to the most vulnerable parts of HIV. The immunogen, called ‘HTI’, was designed by Dr Christian Brander, co-founder and CSO of AELIX Therapeutics, and his co-workers. It is based on the observation that T-cell response to certain parts of some HIV proteins are enriched in individuals with enhanced natural control of their HIV infection. The HTI immunogen brings these vulnerable regions together in a single vaccine immunogen sequence designed to induce beneficial T-cell response with superior capacity to control the virus.
The HTI sequence design is driven by immune data from nearly 1,000 individuals living with the HIV infection from four different cohorts on three continents (Mothe et al. 2011). These large datasets helped avoid bias in the final immunogen sequence due to specific host genetics. Furthermore, the HTI design does not rely on assumptions regarding the importance of conserved viral gene sequences either, as it is based on functional immune data. However, many HTI segments are highly conserved and therefore cover large proportions of the global HIV diversity.
The predictive power of HTI-directed T-cell response on virus control in vivo has been validated in unrelated cohorts and through sub-studies in samples from earlier vaccine trials, such as the STEP trial (Hancock et al. 2015). Furthermore, preclinical data shows that HTI immunisation in mice and macaques elicits strong and broadly directed T-cell responses that have been associated with HIV-1 control in previous human studies (Mothe et al. 2015).