title: Comparison of multiple adjuvants on the stability and immunogenicity of a clade C HIV-1 gp140 trimer.
abstract: Immunogens based on the human immunodeficiency virus type-1 (HIV-1) Envelope (Env) glycoprotein have to date failed to elicit potent and broadly neutralizing antibodies against diverse HIV-1 strains. An understudied area in the development of HIV-1 Env-based vaccines is the impact of various adjuvants on the stability of the Env immunogen and the magnitude of the induced humoral immune response. We hypothesize that optimal adjuvants for HIV-1 gp140 Env trimers will be those with high potency but also those that preserve structural integrity of the immunogen and those that have a straightforward path to clinical testing. In this report, we systematically evaluate the impact of 12 adjuvants on the stability and immunogenicity of a clade C (CZA97.012) HIV-1 gp140 trimer in guinea pigs and a subset in non-human primates. Oil-in-water emulsions (GLA-emulsion, Ribi, Emulsigen) resulted in partial aggregation and loss of structural integrity of the gp140 trimer. In contrast, alum (GLA-alum, Adju-Phos, Alhydrogel), TLR (GLA-aqueous, CpG, MPLA), ISCOM (Matrix M) and liposomal (GLA-liposomes, virosomes) adjuvants appeared to preserve trimer integrity as measured by size exclusion chromatography. However, multiple classes of adjuvants similarly augmented Env-specific binding and neutralizing antibody responses in guinea pigs and non-human primates.
authors.affiliation: Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Nkolola
authors.affiliation: Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Darrick
authors.initials: D
authors.lastname: Carter
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Reed
authors.affiliation: Crucell, 2301 CA Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Crucell, 2301 CA Leiden, The Netherlands.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Division of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT and Harvard, Boston, MA 02114, USA. Electronic address: dbarouch@bidmc.harvard.edu.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000917:Antibody Formation; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood*; D009500:Neutralization Tests; D055550:Protein Stability; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1
keywords: Adjuvants; Env; HIV-1