Generating and measuring effective vaccine-elicited HIV-specific CD8(+) T cell responses

PURPOSE OF REVIEW: There is growing consensus that eliciting CD8(+) T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8(+) T cells as well as major CD8(+) T cell-based delivery platforms used in recent HIV vaccine clinical trials. RECENT FINDINGS: Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8(+) T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8(+) T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8(+) T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials. SUMMARY: Identifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8(+) T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8(+) T cell-based vaccines for HIV.