title: A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein.
abstract: A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences.
authors: Department of Infectious Diseases, Maxygen, Inc., Redwood City, California, United States of America.
authors: Sean X
authors: SX
authors: Du
authors: Li
authors: L
authors: Xu
authors: Wenge
authors: W
authors: Zhang
authors: Susan
authors: S
authors: Tang
authors: Rebecca I
authors: RI
authors: Boenig
authors: Helen
authors: H
authors: Chen
authors: Ellaine B
authors: EB
authors: Mariano
authors: Michael B
authors: MB
authors: Zwick
authors: Paul W H I
authors: PW
authors: Parren
authors: Dennis R
authors: DR
authors: Burton
authors: Terri
authors: T
authors: Wrin
authors: Christos J
authors: CJ
authors: Petropoulos
authors: John A
authors: JA
authors: Ballantyne
authors: Michael
authors: M
authors: Chambers
authors: Robert G
authors: RG
authors: Whalen
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019143:Evolution, Molecular; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011817:Rabbits; D020349:Surface Plasmon Resonance
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120