title: Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer.
abstract: The extraordinary diversity of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein poses a major challenge for the development of an HIV-1 vaccine. One strategy to circumvent this problem utilizes bioinformatically optimized mosaic antigens. However, mosaic Env proteins expressed as trimers have not been previously evaluated for their stability, antigenicity, and immunogenicity. Here, we report the production and characterization of a stable HIV-1 mosaic M gp140 Env trimer. The mosaic M trimer bound CD4 as well as multiple broadly neutralizing monoclonal antibodies, and biophysical characterization suggested substantial stability. The mosaic M trimer elicited higher neutralizing antibody (nAb) titers against clade B viruses than a previously described clade C (C97ZA.012) gp140 trimer in guinea pigs, whereas the clade C trimer elicited higher nAb titers than the mosaic M trimer against clade A and C viruses. A mixture of the clade C and mosaic M trimers elicited nAb responses that were comparable to the better component of the mixture for each virus tested. These data suggest that combinations of relatively small numbers of immunologically complementary Env trimers may improve nAb responses.
  
  
  OBJECTIVE
  The development of an HIV-1 vaccine remains a formidable challenge due to multiple circulating strains of HIV-1 worldwide. This study describes a candidate HIV-1 Env protein vaccine whose sequence has been designed by computational methods to address HIV-1 diversity. The characteristics and immunogenicity of this Env protein, both alone and mixed together with a clade C Env protein vaccine, are described.
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Joseph P
authors: JP
authors: Nkolola
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Christine A
authors: CA
authors: Bricault
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Ann
authors: A
authors: Cheung
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Jennifer
authors: J
authors: Shields
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: James
authors: J
authors: Perry
authors: Division of Molecular Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors: James M
authors: JM
authors: Kovacs
authors: Theoretical Biology and Biophysics, Los Alamos National Laboratory, and the New Mexico Consortium, Los Alamos, New Mexico, USA.
authors: Elena
authors: E
authors: Giorgi
authors: Crucell Vaccine Institute, Leiden, The Netherlands.
authors: Margot
authors: M
authors: van Winsen
authors: Crucell Vaccine Institute, Leiden, The Netherlands.
authors: Adrian
authors: A
authors: Apetri
authors: Crucell Vaccine Institute, Leiden, The Netherlands.
authors: Els C M
authors: EC
authors: Brinkman-van der Linden
authors: Division of Molecular Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors: Bing
authors: B
authors: Chen
authors: Theoretical Biology and Biophysics, Los Alamos National Laboratory, and the New Mexico Consortium, Los Alamos, New Mexico, USA.
authors: Bette
authors: B
authors: Korber
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Michael S
authors: MS
authors: Seaman
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, USA dbarouch@bidmc.harvard.edu.
authors: Dan H
authors: DH
authors: Barouch
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1