Cytotoxic T-lymphocyte escape monitoring in simian immunodeficiency virus vaccine challenge studies.
Several vaccine studies have ameliorated disease progression in simian-human immunodeficiency virus (SHIV) infections. The successes of these vaccines have been largely attributed to protective effects of cytotoxic T-lymphocyte (CTL) responses, although the precise correlates of immune protection remain poorly defined. It is now well established that vigorous CTL and antibody responses can rapidly select for viral escape variants after HIV and SIV infection. Here we suggest that viral variation analyses should be performed on viruses derived from vaccinated, SIV-, or SHIV-challenged animals as a routine component of vaccine evaluation to determine the contribution of immune responses to the success (or failure) of the vaccine regimen. To illustrate the importance of escape analysis, we show that rapid emergence of escape variants postchallenge contributed to the failure of a DNA prime/MVA boost vaccine regimen encoding SIV Tat.
O'Connor
David H
DH
University of Wisconsin at Madison, Department of Pathology, Madison, Wisconsin 53709, USA. doconnor@primate.wisc.edu
Allen
Todd M
TM
Watkins
David I
DI
D000818:Animals; D015696:Gene Products, tat / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014765:Viral Vaccines; D054322:tat Gene Products, Human Immunodeficiency Virus