Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

Matthew R Reynolds; Andrea M Weiler; Kim L Weisgrau; Shari M Piaskowski; Jessica R Furlott; Jason T Weinfurter; Masahiko Kaizu; Taeko Soma; Enrique J León; Caitlin MacNair; Dan P Leaman; Michael B Zwick; Emma Gostick; Solomon K Musani; David A Price; Thomas C Friedrich; Eva G Rakasz; Nancy A Wilson; Adrian B McDermott; Rosanne Boyle; David B Allison; Dennis R Burton; Wayne C Koff; David I Watkins

doi:10.1084/jem.20081524

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Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

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Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

Matthew R Reynolds, Andrea M Weiler, Kim L Weisgrau, Shari M Piaskowski, Jessica R Furlott, Jason T Weinfurter, Masahiko Kaizu, Taeko Soma, Enrique J León, Caitlin MacNair, …

The Journal of experimental medicine, Vol.205(11), pp.2537-2550

2008-10-27

DOI: https://doi.org/10.1084/jem.20081524

PMCID: PMC2571929

PMID: 18838548

Abstract

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 ∼2 logs between weeks 2–32 (P ≤ 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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV-1
Web Of Science research areas: Immunology; Medicine, Research & Experimental
ESI research areas: Immunology

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Title: Macaques vaccinated with live-attenuated SIV control replication of heterologous virus
Creators: Matthew R Reynolds - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Andrea M Weiler - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Kim L Weisgrau - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Shari M Piaskowski - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Jessica R Furlott - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Jason T Weinfurter - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Masahiko Kaizu - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Taeko Soma - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Enrique J León - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Caitlin MacNair - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Dan P Leaman - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
Michael B Zwick - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
Emma Gostick - Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK
Solomon K Musani - Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294
David A Price - Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK
Thomas C Friedrich - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Eva G Rakasz - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Nancy A Wilson - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
Adrian B McDermott - International AIDS Vaccine Initiative, New York, NY 10038
Rosanne Boyle - International AIDS Vaccine Initiative, New York, NY 10038
David B Allison - Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294
Dennis R Burton - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
Wayne C Koff - International AIDS Vaccine Initiative, New York, NY 10038
David I Watkins - AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706
Publication Details: The Journal of experimental medicine, Vol.205(11), pp.2537-2550
Academic Unit: UMMG Department of Pathology
Language: English
Resource Type: Journal article
PMID: 18838548
PMCID: PMC2571929
Record Identifier: 991031599876502976