Designing optimal HIV-vaccine T-cell responses

T cells can efficaciously control HIV replication, and it has been hypothesized that inducing those responses before exposure occurs may prevent HIV infection. However, conventional attempts to generate protective CD8 T-cell responses against HIV have generally failed. Based on current knowledge from chronic HIV infection and previous vaccine trials, this review details optimal CD8 and CD4 T-cell response design that may confer protection from HIV infection.

The failure of two vaccines geared toward inducing T-cell response (STEP trial and HVTN505/Phambili) as well as the modest protection of the RV144 that mainly demonstrated nonneutralizing antibodies to be a correlate of protection have rattled the idea that a pure T-cell-based vaccine may induce protection. Moreover, in the recent years, CD4 T cells, and in particular the T follicular helper cell subset, received attention as a critical component for T-cell-inducing and antibody-inducing vaccines.

It is apparent that all vaccines depend for their efficacy on a cellular component either to directly kill virally infected cells or to provide important helper signals for the development of efficacious B-cell responses. Recent vaccine trials have had a major impact on the field and are guiding new approaches for HIV vaccine design.