title: Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies.
abstract: The restricted neutralization breadth of vaccine-elicited antibodies is a major limitation of current human immunodeficiency virus-1 (HIV-1) candidate vaccines. In order to permit the efficient identification of vaccines with enhanced capacity for eliciting cross-reactive neutralizing antibodies (NAbs) and to assess the overall breadth and potency of vaccine-elicited NAb reactivity, we assembled a panel of 109 molecularly cloned HIV-1 Env pseudoviruses representing a broad range of genetic and geographic diversity. Viral isolates from all major circulating genetic subtypes were included, as were viruses derived shortly after transmission and during the early and chronic stages of infection. We assembled a panel of genetically diverse HIV-1-positive (HIV-1(+)) plasma pools to assess the neutralization sensitivities of the entire virus panel. When the viruses were rank ordered according to the average sensitivity to neutralization by the HIV-1(+) plasmas, a continuum of average sensitivity was observed. Clustering analysis of the patterns of sensitivity defined four subgroups of viruses: those having very high (tier 1A), above-average (tier 1B), moderate (tier 2), or low (tier 3) sensitivity to antibody-mediated neutralization. We also investigated potential associations between characteristics of the viral isolates (clade, stage of infection, and source of virus) and sensitivity to NAb. In particular, higher levels of NAb activity were observed when the virus and plasma pool were matched in clade. These data provide the first systematic assessment of the overall neutralization sensitivities of a genetically and geographically diverse panel of circulating HIV-1 strains. These reference viruses can facilitate the systematic characterization of NAb responses elicited by candidate vaccine immunogens.
authors: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. mseaman@bidmc.harvard.edu
authors: Michael S
authors: MS
authors: Seaman
authors: Holly
authors: H
authors: Janes
authors: Natalie
authors: N
authors: Hawkins
authors: Lauren E
authors: LE
authors: Grandpre
authors: Colleen
authors: C
authors: Devoy
authors: Ayush
authors: A
authors: Giri
authors: Rory T
authors: RT
authors: Coffey
authors: Linda
authors: L
authors: Harris
authors: Blake
authors: B
authors: Wood
authors: Marcus G
authors: MG
authors: Daniels
authors: Tanmoy
authors: T
authors: Bhattacharya
authors: Alan
authors: A
authors: Lapedes
authors: Victoria R
authors: VR
authors: Polonis
authors: Francine E
authors: FE
authors: McCutchan
authors: Peter B
authors: PB
authors: Gilbert
authors: Steve G
authors: SG
authors: Self
authors: Bette T
authors: BT
authors: Korber
authors: David C
authors: DC
authors: Montefiori
authors: John R
authors: JR
authors: Mascola
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D002460:Cell Line; D015686:Gene Products, env / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D015686:Gene Products, env