Review article Memories that last forever: strategies for optimizing vaccine T-cell memory

For acute self-limiting infections a vac-cine is successful if it elicits memory at least as good as the natural experience; however, for persistent and chronic infec-tions such as HIV, hepatitis C virus (HCV), human papillomavirus (HPV), and human herpes viruses, this paradigm is not appli-cable. At best, during persistent virus infection the person must be able to main-tain the integrity of the immune system in equilibrium with controlling replicating virus. New vaccine strategies are re-quired that elicit both potent high-avidity CD8 T-cell effector/memory and central memory responses that can clear the nidus of initial virus-infected cells at mu-cosal surfaces to prevent mucosal trans-mission or significantly curtail develop-ment of disease. The objective of an HIV-1 T-cell vaccine is to generate functional CD8 effector memory cells at mucosal portals of virus entry to prevent viral transmission. In addition, long-lived CD8 and CD4 central memory cells circulat-ing through secondary lymphoid organs and resident in bone marrow, respec-tively, are needed to provide a concerted second wave of defense that can contain virus at mucosal surfaces and prevent systemic dissemination. Further under-standing of factors which can influence long-lived effector and central memory cell differentiation will significantly con-tribute to development of effective T-cell vaccines. In this review we will focus on discussing mechanisms involved in T-cell memory and provide promising new approaches toward expanding current vaccine strategies to enhance antiviral memory. (Blood. 2010;115:1678-1689