Macaques vaccinated with live-attenuated SIV control replication of heterologous virus.
An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8(+) T cells in this control. Furthermore, transient depletion of peripheral CD8(+) lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.
AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA. mrreynol@wisc.edu
Matthew R
MR
Reynolds
Andrea M
AM
Weiler
Kim L
KL
Weisgrau
Shari M
SM
Piaskowski
Jessica R
JR
Furlott
Jason T
JT
Weinfurter
Masahiko
M
Kaizu
Taeko
T
Soma
Enrique J
EJ
León
Caitlin
C
MacNair
Dan P
DP
Leaman
Michael B
MB
Zwick
Emma
E
Gostick
Solomon K
SK
Musani
David A
DA
Price
Thomas C
TC
Friedrich
Eva G
EG
Rakasz
Nancy A
NA
Wilson
Adrian B
AB
McDermott
Rosanne
R
Boyle
David B
DB
Allison
Dennis R
DR
Burton
Wayne C
WC
Koff
David I
DI
Watkins
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D014644:Genetic Variation; D008251:Macaca; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D017423:Sequence Analysis, RNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000502:physiology*
D017931:DNA Primers; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated