title: Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA. nwilson@primate.wisc.edu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Jason S
authors.initials: JS
authors.lastname: Reed
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: MacNair
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bett
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thoryk
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Heidecker
authors.forename: Michael P
authors.initials: MP
authors.lastname: Citron
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vitelli
authors.forename: Chanook D
authors.initials: CD
authors.lastname: Ahn
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kaizu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maness
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Reynolds
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: John T
authors.initials: JT
authors.lastname: Loffredo
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.forename: Stephen
authors.initials: S
authors.lastname: Erickson
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D018449:SAIDS Vaccines / Q000276:immunology*; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA