Cytomegalovirus Vectors Violate CD8 + T Cell Epitope Recognition Paradigms

Abstract

CMV Breaks All the Rules One vaccine strategy being pursued against HIV is to generate protection that is dependent on cell-mediated, rather than humoral, immune responses. A cytomegalovirus (CMV)–vectored vaccine that expresses simian immunodeficiency virus (SIV) antigens exhibits stringent and durable viral control upon SIV challenge in approximately half of vaccinated rhesus macaques. Hansen et al. ( 10.1126/science.1237874 , see the Perspective by Goonetilleke and McMichael ) sought to determine the basis for the protection and discovered that the CD8 + T cell response in vaccinated monkeys does not target canonical SIV epitopes, which SIV is known to escape, but rather generates a broad, promiscuous response.