title: Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 Envelope glycoprotein trimers on neutralizing antibody induction.
abstract: Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits (PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to improve nAb responses by removing the N362 glycan that also lines the CD4bs. All 4 rabbits developed nAbs. One targeted the N197 glycan hole like our previous sera. Two sera depended on the N463 glycan, again suggesting CD4bs overlap. Heterologous boosts appeared to reduce nAb clashes with the N362 glycan. The fourth serum targeted a N362 glycan-sensitive epitope. VLP manufacture challenges prevented us from immunizing larger rabbit numbers to empower a robust statistical analysis. Nevertheless, trends suggest that targeted glycan removal may improve nAb induction by exposing new epitopes and that it may be possible to modify nAb specificity using rational heterologous boosts.
authors.affiliation: San Diego Biomedical Research Institute, 10865 Road to the Cure, San Diego, CA 92121, USA.
authors.forename: Ema T
authors.initials: ET
authors.lastname: Crooks
authors.affiliation: San Diego Biomedical Research Institute, 10865 Road to the Cure, San Diego, CA 92121, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Osawa
authors.affiliation: San Diego Biomedical Research Institute, 10865 Road to the Cure, San Diego, CA 92121, USA.
authors.forename: Tommy
authors.initials: T
authors.lastname: Tong
authors.affiliation: San Diego Biomedical Research Institute, 10865 Road to the Cure, San Diego, CA 92121, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Grimley
authors.affiliation: The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yang D
authors.initials: YD
authors.lastname: Dai
authors.affiliation: Altravax, Inc., 725 San Aleso Avenue, Suite 2, Sunnyvale, CA 94085, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Whalen
authors.affiliation: IAVI Neutralizing Antibody Center at The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Kulp
authors.affiliation: IAVI Neutralizing Antibody Center at The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Menis
authors.affiliation: IAVI Neutralizing Antibody Center at The Scripps Research Institute, Department of Immunology and Microbial Science, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Schief
authors.affiliation: San Diego Biomedical Research Institute, 10865 Road to the Cure, San Diego, CA 92121, USA. Electronic address: jbinley@sdbri.org.
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D009500:Neutralization Tests; D011817:Rabbits
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41
keywords: Antibody; Env, trimer; Glycan; Gp120, neutralization; HIV-1; VLP; Vaccine