Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge

Nancy A Wilson; Brandon F Keele; Jason S Reed; Shari M Piaskowski; Caitlin E MacNair; Andrew J Bett; Xiaoping Liang; Fubao Wang; Elizabeth Thoryk; Gwendolyn J Heidecker; Michael P Citron; Lingyi Huang; Jing Lin; Salvatore Vitelli; Chanook D Ahn; Masahiko Kaizu; Nicholas J Maness; Matthew R Reynolds; Thomas C Friedrich; John T Loffredo; Eva G Rakasz; Stephen Erickson; David B Allison; Michael Piatak; Jeffrey D Lifson; John W Shiver; Danilo R Casimiro; George M Shaw; Beatrice H Hahn; David I Watkins

doi:10.1128/JVI.00272-09

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Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge

Journal article

Open access

Peer reviewed

Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge

Nancy A Wilson, Brandon F Keele, Jason S Reed, Shari M Piaskowski, Caitlin E MacNair, Andrew J Bett, Xiaoping Liang, Fubao Wang, Elizabeth Thoryk, Gwendolyn J Heidecker, …

Journal of virology, Vol.83(13), pp.6508-6521

2009-07

DOI: https://doi.org/10.1128/JVI.00272-09

PMCID: PMC2698536

PMID: 19403685

Abstract

Vaccines and Antiviral Agents

All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended in failure. Structural features of the Env glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of a heterologous, mucosal viral challenge, we vaccinated eight macaques with a DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env. Vaccinees mounted high-frequency T-cell responses against 11 to 34 epitopes. We challenged the vaccinees and eight naïve animals with the heterologous biological isolate SIVsmE660, using a regimen intended to mimic typical HIV exposures resulting in infection. Viral loads in the vaccinees were significantly less at both the peak (1.9-log reduction; P < 0.03) and at the set point (2.6-log reduction; P < 0.006) than those in control naïve animals. Five of eight vaccinated macaques controlled acute peak viral replication to less than 80,000 viral RNA (vRNA) copy eq/ml and to less than 100 vRNA copy eq/ml in the chronic phase. Our results demonstrate that broad vaccine-induced cellular immune responses can effectively control replication of a pathogenic, heterologous AIDS virus, suggesting that T-cell-based vaccines may have greater potential than previously appreciated.

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Collaboration types: Industry collaboration; Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV-1
Web Of Science research areas: Virology
ESI research areas: Microbiology

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Title: Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge
Creators: Nancy A Wilson - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Brandon F Keele - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Jason S Reed - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Shari M Piaskowski - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Caitlin E MacNair - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Andrew J Bett - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Xiaoping Liang - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Fubao Wang - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Elizabeth Thoryk - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Gwendolyn J Heidecker - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Michael P Citron - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Lingyi Huang - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Jing Lin - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Salvatore Vitelli - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Chanook D Ahn - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Masahiko Kaizu - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Nicholas J Maness - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Matthew R Reynolds - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Thomas C Friedrich - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
John T Loffredo - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Eva G Rakasz - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Stephen Erickson - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
David B Allison - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Michael Piatak - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Jeffrey D Lifson - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
John W Shiver - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Danilo R Casimiro - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
George M Shaw - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Beatrice H Hahn - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
David I Watkins - Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin
Publication Details: Journal of virology, Vol.83(13), pp.6508-6521
Publisher: American Society for Microbiology (ASM)
Academic Unit: UMMG Department of Pathology
Language: English
Resource Type: Journal article
PMID: 19403685
PMCID: PMC2698536
Record Identifier: 991031600413602976