Simon Hoffenberg
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View article: Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes
Identification of an HIV-1 Clade A Envelope That Exhibits Broad Antigenicity and Neutralization Sensitivity and Elicits Antibodies Targeting Three Distinct Epitopes Open
Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both antibodies are highly potent…
View article: Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9
Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9 Open
PG9 is the founder member of an expanding family of glycan-dependent human antibodies that preferentially bind the HIV (HIV-1) envelope (Env) glycoprotein (gp) trimer and broadly neutralize the virus. Here, we show that a soluble SOSIP.664…
View article: Rapid, Quantitative Mapping of Anti-HIV Type 1 Envelope Serum Antibody Specificities
Rapid, Quantitative Mapping of Anti-HIV Type 1 Envelope Serum Antibody Specificities Open
A new generation of extremely broad and potent neutralizing antibodies (bNAbs) has been isolated from HIV-infected subjects. This has refocused interest in the sites of vulnerability targeted by these bNAbs and in the potential for designi…
View article: Inverse dose-response to gp140 YU2 foldon trimer formulated with aluminum phosphate and ISCOMATRIX® adjuvants
Inverse dose-response to gp140 YU2 foldon trimer formulated with aluminum phosphate and ISCOMATRIX® adjuvants Open
Background Conventional vaccine approaches based on delivery of HIV-1 envelope (Env) proteins or peptides derived from Env sequences have failed to generate broadly neutralizing antibodies (bNAbs) to the virus. Even with large doses (200 u…
View article: Viral vector delivery of Env trimer immunogens
Viral vector delivery of Env trimer immunogens Open
Methods We are using vesicular stomatitis virus (VSV) as a vector platform for delivery of Env immunogens as transmembrane glycoproteins. We have investigated a variety of vector designs and Env modifications to identify combinations that …
View article: Optimizing expression of functional HIV envelopes in rVSV-ΔG vaccine vectors
Optimizing expression of functional HIV envelopes in rVSV-ΔG vaccine vectors Open
Methods Using a combination of nucleotide sequence optimization and protein domain swapping, we have generated a panel of novel gene inserts for VSV vectors that encode chimeric HIV-1 and VSV glycoprotein immunogens (EnvG). A stable VERO c…
View article: Identification of a clade A HIV envelope immunogen from Protocol G that elicits neutralizing antibodies to tier 2 viruses
Identification of a clade A HIV envelope immunogen from Protocol G that elicits neutralizing antibodies to tier 2 viruses Open
Background Broadly neutralizing antibodies PG9 and PG16 have been isolated from the B cells of one clade A-infected individual from IAVI Protocol G. PG16 is relatively trimer-specific whereas PG9 binds trimer preferentially, but can bind m…
View article: A Novel Membrane-anchored Rab5 Interacting Protein Required for Homotypic Endosome Fusion
A Novel Membrane-anchored Rab5 Interacting Protein Required for Homotypic Endosome Fusion Open
The ras-related GTPase rab5 is rate-limiting for homotypic early endosome fusion. We used a yeast two-hybrid screen to identify a rab5 interacting protein, rab5ip. The cDNA sequence encodes a ubiquitous 75-kDa protein with an N-terminal tr…
View article: Conformationally variable Rab protein surface regions mapped by limited proteolysis and homology modelling
Conformationally variable Rab protein surface regions mapped by limited proteolysis and homology modelling Open
Tryptic proteolysis of the small GTPases Rab4 and Rab5 is a multi-step, nucleotide-dependent process. Using N-terminal peptide sequencing, matrix-assisted laser desorption ionization–time-of-flight MS and molecular modelling, we identified…
View article: Evidence for a Symmetrical Requirement for Rab5-GTP in in Vitro Endosome-Endosome Fusion
Evidence for a Symmetrical Requirement for Rab5-GTP in in Vitro Endosome-Endosome Fusion Open
Early endosome fusion, which has been extensively characterized using an in vitro reconstitution assay, is Rab5-dependent. To examine the requirement for Rab5 on both fusion partners, we prepared cytosol and endosomes depleted of Rab5. Unl…
View article: Biochemical and Functional Characterization of a Recombinant GTPase, Rab5, and Two of Its Mutants
Biochemical and Functional Characterization of a Recombinant GTPase, Rab5, and Two of Its Mutants Open
Biochemical, structural, and functional properties of Rab5 wild-type (WT) protein were compared with those of Q79L and N133I mutants. The detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate increased guanine nucleotide bind…
View article: The 65‐kDa protein from pig heart A new substrate for <i>Clostridium botulinum</i> ADP‐ribosyltransferase (exoenzyme C<sub>3</sub>)
The 65‐kDa protein from pig heart A new substrate for <i>Clostridium botulinum</i> ADP‐ribosyltransferase (exoenzyme C<sub>3</sub>) Open
In the pig heart sarcolemma, a 65 kDa protein is found to be ADP‐ribosylated by Clostridium botulinum ADP‐ribosyltransferase (exoenzyme C 3 ). ADP‐ribosylation of this protein is regulated by guanyl nucleotides and cytosol factor in a fash…