title: Most rhesus macaques infected with the CCR5-tropic SHIV(AD8) generate cross-reactive antibodies that neutralize multiple HIV-1 strains.
abstract: The induction of broadly reacting neutralizing antibodies has been a major goal of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic SIV/HIV chimeric virus (SHIV) molecular clone (SHIV(AD8-EO)) revealed that eight of eight infected animals developed cross-reactive neutralizing antibodies (NAbs) directed against an envelope glycoprotein derived from the heterologous HIV-1(DH12) strain. A panel of plasmas, collected from monkeys inoculated with either molecularly cloned or uncloned SHIV(AD8) stocks, exhibited cross-neutralization against multiple tier 1 and tier 2 HIV-1 clade B isolates. One SHIV(AD8)-infected animal also developed NAbs against clades A and C HIV-1 strains. In this particular infected macaque, the cross-reacting anti-HIV-1 NAbs produced between weeks 7 and 13 were directed against a neutralization-sensitive virus strain, whereas neutralizing activities emerging at weeks 41-51 targeted more neutralization-resistant HIV-1 isolates. These results indicate that the SHIV(AD8) macaque model represents a potentially valuable experimental system for investigating B-cell maturation and the induction of cross-reactive NAbs directed against multiple HIV-1 strains.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shingai
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gautam
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Plishka
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Reza
authors.initials: R
authors.lastname: Sadjadpour
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Lee
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D003429:Cross Reactions; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016130:Immunophenotyping; D008253:Macaca mulatta; D019713:Receptors, CCR5 / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D019713:Receptors, CCR5