title: Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.
abstract: The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the β strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. hliao@duke.edu
authors: Hua-Xin
authors: HX
authors: Liao
authors: Mattia
authors: M
authors: Bonsignori
authors: S Munir
authors: SM
authors: Alam
authors: Jason S
authors: JS
authors: McLellan
authors: Georgia D
authors: GD
authors: Tomaras
authors: M Anthony
authors: MA
authors: Moody
authors: Daniel M
authors: DM
authors: Kozink
authors: Kwan-Ki
authors: KK
authors: Hwang
authors: Xi
authors: X
authors: Chen
authors: Chun-Yen
authors: CY
authors: Tsao
authors: Pinghuang
authors: P
authors: Liu
authors: Xiaozhi
authors: X
authors: Lu
authors: Robert J
authors: RJ
authors: Parks
authors: David C
authors: DC
authors: Montefiori
authors: Guido
authors: G
authors: Ferrari
authors: Justin
authors: J
authors: Pollara
authors: Mangala
authors: M
authors: Rao
authors: Kristina K
authors: KK
authors: Peachman
authors: Sampa
authors: S
authors: Santra
authors: Norman L
authors: NL
authors: Letvin
authors: Nicos
authors: N
authors: Karasavvas
authors: Zhi-Yong
authors: ZY
authors: Yang
authors: Kaifan
authors: K
authors: Dai
authors: Marie
authors: M
authors: Pancera
authors: Jason
authors: J
authors: Gorman
authors: Kevin
authors: K
authors: Wiehe
authors: Nathan I
authors: NI
authors: Nicely
authors: Supachai
authors: S
authors: Rerks-Ngarm
authors: Sorachai
authors: S
authors: Nitayaphan
authors: Jaranit
authors: J
authors: Kaewkungwal
authors: Punnee
authors: P
authors: Pitisuttithum
authors: James
authors: J
authors: Tartaglia
authors: Faruk
authors: F
authors: Sinangil
authors: Jerome H
authors: JH
authors: Kim
authors: Nelson L
authors: NL
authors: Michael
authors: Thomas B
authors: TB
authors: Kepler
authors: Peter D
authors: PD
authors: Kwong
authors: John R
authors: JR
authors: Mascola
authors: Gary J
authors: GJ
authors: Nabel
authors: Abraham
authors: A
authors: Pinter
authors: Susan
authors: S
authors: Zolla-Pazner
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010455:Peptides