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Journal of Virology, September 1999, p. 7524-7532, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effective Induction of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Macaques by Using a Multiepitope Gene and DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccination Regimen

Tomas Hanke,1,* Rachel V. Samuel,1 Tom J. Blanchard,2,dagger Veronica C. Neumann,3 Todd M. Allen,4 Jon E. Boyson,4 Sally A. Sharpe,5 Nicola Cook,5 Geoffrey L. Smith,2 David I. Watkins,4 Martin P. Cranage,5 and Andrew J. McMichael1

Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS,1 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE,2 and Centre for Applied Microbiology and Research, Porton Down, Salisbury SP4 0JG,5 United Kingdom; PowderJect Vaccines, Inc., Madison, Wisconsin 537113; and Wisconsin Regional Primate Research Center, University of Wisconsin---Madison, Madison, Wisconsin 537154

Received 8 April 1999/Accepted 16 June 1999

DNA and modified vaccinia virus Ankara (MVA) are vaccine vehicles suitable and safe for use in humans. Here, by using a multicytotoxic T-lymphocyte (CTL) epitope gene and a DNA prime-MVA boost vaccination regimen, high levels of CTLs specific for a single simian immunodeficiency virus (SIV) gag-derived epitope were elicited in rhesus macaques. These vaccine-induced CTLs were capable of killing SIV-infected cells in vitro. Fluorescence-activated cell sorter analysis using soluble tetrameric major histocompatibility complex-peptide complexes showed that the vaccinated animals had 1 to 5% circulating CD8+ lymphocytes specific for the vaccine epitope, frequencies comparable to those in SIV-infected monkeys. Upon intrarectal challenge with pathogenic SIVmac251, no evidence for protection was observed in at least two of the three vaccinated animals. This study does not attempt to define correlates of protective immunity nor design a protective vaccine against immunodeficiency viruses, but it demonstrates clearly that the DNA prime-MVA boost regimen is an effective protocol for induction of CTLs in macaques. It also shows that powerful tools for studying the role of CTLs in the control of SIV 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 cells. The advantages of the DNA prime-MVA boost regimen as well as the correlations of tetramer staining of peripheral blood lymphocytes with CTL killing in vitro and postchallenge control of viremia are discussed.

* Corresponding author. Mailing address: Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom. Phone: (1865) 222334. Fax: (1865) 222502. E-mail: thanke{at}molbiol.ox.ac.uk.

dagger Present address: MRC Laboratories, Fajara, Banjul, The Gambia, West Africa.

Journal of Virology, September 1999, p. 7524-7532, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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