title: A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251.
abstract: As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (10(6.8) versus 10(8.3) copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (10(3) to 10(4) RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8(+) cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection.
authors.affiliation: California National Primate Research Center, University of California, Davis, California, USA.
authors.forename: Koen K A
authors.initials: KK
authors.lastname: Van Rompay
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hunter
authors.forename: Kartika
authors.initials: K
authors.lastname: Jayashankar
authors.forename: Julianne
authors.initials: J
authors.lastname: Peabody
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Kara
authors.initials: K
authors.lastname: Jensen
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
authors.forename: Bryce
authors.initials: B
authors.lastname: Chackerian
mesh_terms: D000282:Administration, Intravaginal; D017908:Allolevivirus; D000595:Amino Acid Sequence; D000818:Animals; D007074:Immunoglobulin G / Q000276:immunology*; D008253:Macaca mulatta / Q000821:virology; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D010455:Peptides; D012367:RNA, Viral; D019713:Receptors, CCR5; D014765:Viral Vaccines