HIVACAT T-cell Immunogen (HTI) (HTI)

The HIVACAT T-cell Immunogen (HTI) is a synthetic immunogen designed to redirect the host immune response toward 16 highly conserved regions of the HIV-1 proteome (Mothe et al., 2011). These regions, derived from the Gag, Pol, Vif, and Nef proteins, were selected based on their frequent targeting by T-cells in 'elite controllers'—individuals who naturally suppress HIV-1 replication without antiretroviral therapy (ART) (Mothe et al., 2015). By focusing the immune system on these conserved epitopes, the HTI immunogen aims to prevent the virus from escaping immune pressure through mutation, as changes in these critical regions typically result in significant loss of viral fitness (Bailon et al., 2022). In clinical development, HTI is delivered using various vaccine vectors, including DNA, Modified Vaccinia Ankara (MVA), and Chimpanzee Adenovirus (ChAdOx1), often in a heterologous prime-boost regimen (NCT03204617). These vaccines are intended as therapeutic interventions to achieve a 'functional cure,' where the patient's own T-cells maintain viral suppression during periods of ART interruption (AELIX Therapeutics). Clinical trials such as AELIX-002 and AELIX-003 have demonstrated that HTI-based vaccines are safe and can induce robust, polyfunctional CD4+ and CD8+ T-cell responses (Bailon et al., 2022; NCT04364035). While these responses correlate with a delay in viral rebound, achieving sustained remission remains a challenge, leading to ongoing research into combinations with latency-reversing agents or TLR7 agonists like vesatolimod (Gilead Sciences).

Other names

HTI immunogenHIV-1 conserved T-cell epitopesHTI antigenHIVACAT T-cell vaccine

The HTI immunogen works by inducing and refocusing the host's cellular immune response, specifically CD4+ and CD8+ T-cells, toward highly conserved and vulnerable regions of the HIV-1 virus. This strategy aims to mimic the immune profile of 'elite controllers' to achieve a functional cure or sustained viral remission in the absence of antiretroviral therapy.