HIV and SIV CTL escape: implications for vaccine design

Key Points CD8 + T cells (broadly, cytotoxic T lymphocytes, CTLs) have an important role in the control of immunodeficiency virus infection. CTL escape is an important mechanism by which the virus evades the immune response. The occurrence and timing of escape depends on a variety of factors. Similarly, the significance of escape for the patient and for viral evolution is variable, ranging from precipitation to AIDS at one extreme, to successful suppression of viraemia following escape at the other extreme. CTL escape mutations that are most probably of relevance to natural or vaccine-induced immune-mediated control of viraemia are those that occur at a considerable fitness cost to the virus: that is, those that reduce viral replicative capacity. Recent examples of escape followed by immune control of HIV and simian immunodeficiency virus (SIV) are discussed. The consequences for the evolution of HIV of the transmission of viruses that encode escape mutations depend on the fitness cost of the mutation: mutations that result in significantly reduced replication capacity of the virus revert to wild-type following transmission to an HLA-mismatched recipient, whereas mutations that incur little fitness cost probably persist. Mechanisms of mutational escape, including recently described processing mutations, are discussed. CTL escape has implications for vaccine design. The detailed understanding of qualitative differences between CTLs is crucial to determine which epitopes need to be included in a vaccine and which need to be excluded. Cytotoxic T lymphocytes (CTLs) have a central role in the successful control of immunodeficiency virus infection. Evasion of this immune response through CTL escape is therefore an important factor in HIV and simian immunodeficiency virus pathogenesis. During the course of an infection, the precise timing of the occurrence of escape mutations and their location in the viral genome can indicate the efficacy of certain CTL specificities and the cost to viral fitness of particular escape mutations — factors that are highly relevant to vaccine design. Also crucial for vaccine design is the extent to which CTL escape is driving the evolution of HIV at the population level. Here, we highlight the important lessons that can be learned from immunodeficiency virus CTL escape.