title: Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239.
abstract: The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4(+) memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711, USA. nwilson@primate.wisc.edu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Jason
authors.initials: J
authors.lastname: Reed
authors.forename: Gnankang S
authors.initials: GS
authors.lastname: Napoe
authors.forename: Shari
authors.initials: S
authors.lastname: Piaskowski
authors.forename: Andy
authors.initials: A
authors.lastname: Szymanski
authors.forename: Jessica
authors.initials: J
authors.lastname: Furlott
authors.forename: Edna J
authors.initials: EJ
authors.lastname: Gonzalez
authors.forename: Levi J
authors.initials: LJ
authors.lastname: Yant
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maness
authors.forename: Gemma E
authors.initials: GE
authors.lastname: May
authors.forename: Taeko
authors.initials: T
authors.lastname: Soma
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Reynolds
authors.forename: Eva
authors.initials: E
authors.lastname: Rakasz
authors.forename: Richard
authors.initials: R
authors.lastname: Rudersdorf
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Amit
authors.initials: A
authors.lastname: Patki
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Heindecker
authors.forename: Jiang
authors.initials: J
authors.lastname: Fan
authors.forename: Michael
authors.initials: M
authors.lastname: Citron
authors.forename: Melanie
authors.initials: M
authors.lastname: Horton
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D015686:Gene Products, env / Q000008:administration & dosage* / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env; D018449:SAIDS Vaccines