title: Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins.
abstract: The extraordinarily high level of genetic variation of HIV-1 env genes poses a challenge to obtain antibodies that cross-react with multiple subtype Env glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to highly conserved epitopes in HIV-1 envelope glycoproteins can be induced, we immunized mice with wild-type or consensus HIV-1 Env proteins and characterized a panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G, CRF01_AE, and a highly divergent SIVcpzUS Env proteins by ELISA and Western blot analysis. Two mAbs (3B3 and 16H3) cross-reacted with all tested Env proteins, including SIVcpzUS Env. Surface plasmon resonance analyses showed both 3B3 and 16H3 bound Env proteins with high affinity. However, neither neutralized primary HIV-1 pseudoviruses. These data indicate that broadly reactive non-neutralizing monoclonal antibodies can be elicited, but that the conserved epitopes that they recognize are not present on functional virion trimers. Nonetheless, such mAbs represent valuable reagents to study the biochemistry and structural biology of Env protein oligomers.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. fgao@duke.edu
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Bhavna
authors.initials: B
authors.lastname: Hora
authors.forename: Shimao
authors.initials: S
authors.lastname: Xia
authors.forename: Julie E
authors.initials: JE
authors.lastname: Hohm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Damon F
authors.initials: DF
authors.lastname: Ogburn
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Emily
authors.initials: E
authors.lastname: Park
authors.forename: Woodrow E
authors.initials: WE
authors.lastname: Lomas
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Maino
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000915:Antibody Affinity; D003429:Cross Reactions; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D020349:Surface Plasmon Resonance; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus