IL-27 and the generation of CD8+ T-cell responses to peptide vaccines.

Abstract

It can be argued that the greatest increases in human longevity in the last 200 y have been the introduction of public sanitation and vaccination. Success in the latter has minimized the impact of a multitude of pathogens on human health. Historically, vaccine efficacy is equated with the generation of protective antibodies driven by immunization with attenuated pathogens or pathogen-derived toxins. Attenuated pathogens are not always without toxicity, which can lead to poor adoption of vaccines. Additionally, a major 21st century clinical goal is to generate therapeutic immunity to chronic viral infections and cancer. For these diseases, cytotoxic CD8+ T cells, rather than antibodies, could have more utility. As these clinical conditions are often characterized by suboptimal or even compromised systemic immunity, there is considerable interest in developing noninfectious approaches to elicit T-cell responses. The short peptides that T cells recognize, when presented at the cell surface by MHC molecules, have served as the backbone for T-cell vaccines. However, our knowledge of how to immunize for CD8+ T cells is limited; current peptide vaccines, which commonly use adjuvants that were designed to support the generation of antibodies, can promote CD8+ T-cell responses in the range of 1–5% of the CD8+ T-cell population. In contrast, CD8+ T-cell responses to viruses can reach 50% of the total CD8+ T-cell population in a host. By defining the critical components that promote subunit vaccines, such as the critical contribution of IL-27 as reported in PNAS by Pennock et al. (1), mechanistic insight into the regulation of CD8+ T-cell responses and the opportunity to increase vaccine efficacy can be realized.