HIV T-cell immunogen design and delivery

Abstract

Purpose of the review Not all T-cell responses against HIV are created equally and responses of certain epitope specificities have been associated with superior control of infection. These insights have spurred the development of a wide range of immunogen sequences, each with particular advantages and limitations. Recent findingsWe review some of the most advanced designs that have reached or are close to reaching human clinical trials, with a special focus on T-cell immunogen developed for therapeutic use. We also touch upon the importance of how immunogens are delivered and point out the lamentable fact that there is essentially no alignment between different designs and vaccine regimens, which is a major hindrance to accelerated advances in the field.

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

“…Recent advances in developing CD8 þ T cellbased vaccines for HIV cure have been extensively reviewed recently elsewhere [13,14 & ,…”

“…target viral epitopes that are less likely/unable to be mutated and likely target a broad range of these epitopes across HLA types [ 13 , 14 ▪ , 15 ▪ , 32 , 33 ▪ ],…”

“…One clinical trial, HVTN 505 (DNA/Ad5), did report a correlation between Env-specific CD8 + T cell magnitude and polyfunctionality and decreased infection risk (hazard ratio = 0.51 and 0.47, respectively) [ 43 , 44 ]. With regards to epitope targeting, earlier HIV vaccine inserts typically encoded full-length viral proteins, but it is now clear that more narrowly targeting evolutionarily conserved and/or structurally constrained epitopes/regions more efficiently elicits CD8 + T cell responses that are predicted to be less likely to be evaded by viral mutation [ 13 , 14 ▪ , 15 ▪ , 32 , 33 ▪ , 45 , 46 ▪▪ , 47 ]. Some specific HLA class I alleles have been associated with elite controller status or altered rates of disease progression [ 19 , 48 – 50 ].…”

“…In this review, we will describe our understanding of ideal features required for HIV vaccineelicited CD8 þ T cells and what is known about the CD8 þ T cell immunogenicity of current vaccine platforms that seek to elicit robust virus-specific CD8 þ T cell responses. We will not focus on immunogen design, as that has been covered in depth in recent reviews [13,14…”

“…In this review, we will describe our understanding of ideal features required for HIV vaccine-elicited CD8 + T cells and what is known about the CD8 + T cell immunogenicity of current vaccine platforms that seek to elicit robust virus-specific CD8 + T cell responses. We will not focus on immunogen design, as that has been covered in depth in recent reviews [ 13 , 14 ▪ , 15 ▪ ]. We will discuss methods to comprehensively measure the quality of vaccine-elicited CD8 + T cell responses and, finally, we will consider lessons from HIV therapeutic vaccine studies that may inform prevention strategies.…”