Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modifiedvaccinia virus Ankara boost vaccination regimen

DNA and modified vaccinia virus Ankara (MVA) are vaccine vehicles suitable and safe for use in humans. Here, by using a multicytotoxic T-lymphocyte (C TL) epitope gene and a DNA prime-MVA boost vaccination regimen, high levels of CTLs specific for a single simian immunodeficiency virus (SN) gag-deriv ed epitope were elicited in rhesus macaques. These vaccine-induced CTLs wer e capable of killing SIV-infected cells in vitro. Fluorescence-activated ce ll sorter analysis using soluble tetrameric major histocompatibility comple x-peptide complexes showed that the vaccinated animals had 1 to 5% circulat ing CD8(+) lymphocytes specific for the vaccine epitope, frequencies compar able to those in SIV-infected monkeys. Upon intrarectal challenge with path ogenic SIVmac251, no evidence for protection was observed in at least two o f the three vaccinated animals. This study does not attempt to define corre lates of protective immunity nor design a protective vaccine against immuno deficiency viruses, but it demonstrates clearly that the DNA prime-MVA boos t regimen is an effective protocol for induction of CTLs in macaques. It al so shows that powerful tools for studying the role of CTLs in the control o f SN and human immunodeficiency virus infections are now available: epitope -based vaccines, a protocol for an effective induction of CTLs in primates, and a simple and sensitive method for quantitation of epitope-specific T c ells. The advantages of the DNA prime-MVA boost regimen as well as the corr elations of tetramer staining of peripheral blood lymphocytes with CTL kill ing in vitro and postchallenge control of viremia are discussed.