Scholars@Duke
Rory Henderson

Rory Henderson

Associate Professor in Medicine
Medicine, Duke Human Vaccine Institute
rory.henderson@duke.edu
2 Genome Ct, MSRB 2, Durham, NC 27710
2 Genome Ct, MSRB 2, Durham, NC 27710

Selected Publications

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Journal Article Nat Commun · November 3, 2024 Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for ... Full text Link to item Cite

SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition.

Journal Article Mol Cell · July 25, 2024 A recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for the ... Full text Link to item Cite

Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.

Journal Article Cell Host Microbe · May 8, 2024 A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbabl ... Full text Link to item Cite

Microsecond dynamics control the HIV-1 Envelope conformation.

Journal Article Sci Adv · February 2, 2024 The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timesca ... Full text Link to item Cite

Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.

Journal Article Cell · January 4, 2024 The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glyca ... Full text Link to item Cite

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Journal Article bioRxiv · December 30, 2023 Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-and-error search fo ... Full text Link to item Cite

Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.

Journal Article Nat Commun · May 15, 2023 Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens ... Full text Link to item Cite

Network analysis uncovers the communication structure of SARS-CoV-2 spike protein identifying sites for immunogen design.

Journal Article iScience · January 20, 2023 The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand the structure and dynamics of this complex pathogen. The spike glycoprotein of SARS-CoV-2 is a significant target for immunogens as it is the means by which t ... Full text Link to item Cite

Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.

Journal Article Cell Rep · June 28, 2022 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences in their pathobiology, here we determine cryoelectron microsc ... Full text Link to item Cite

Structural diversity of the SARS-CoV-2 Omicron spike.

Journal Article Mol Cell · June 2, 2022 Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor-binding domain (RBD) and neutralizing antib ... Full text Link to item Cite

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Journal Article Cell Rep · March 15, 2022 The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alon ... Full text Link to item Cite

Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.

Journal Article Cell Rep · November 2, 2021 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we is ... Full text Link to item Cite

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.

Journal Article Science · August 6, 2021 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant ... Full text Link to item Cite

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Journal Article Cell · May 27, 2021 Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (b ... Full text Open Access Link to item Cite

HIV-1 Envelope Conformation, Allostery, and Dynamics.

Journal Article Viruses · May 7, 2021 The HIV-1 envelope glycoprotein (Env) mediates host cell fusion and is the primary target for HIV-1 vaccine design. The Env undergoes a series of functionally important conformational rearrangements upon engagement of its host cell receptor, CD4. As the so ... Full text Link to item Cite

Cold sensitivity of the SARS-CoV-2 spike ectodomain.

Journal Article Nat Struct Mol Biol · February 2021 The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its receptor binding domain in two conformations, the receptor-accessible 'up' or receptor-inaccessible 'down' states. Here we report that the commonly used stabi ... Full text Link to item Cite

D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction.

Journal Article Cell Rep · January 12, 2021 The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein ap ... Full text Link to item Cite

Controlling the SARS-CoV-2 spike glycoprotein conformation.

Journal Article Nat Struct Mol Biol · October 2020 The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a ... Full text Link to item Cite

Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.

Journal Article Nat Commun · January 24, 2020 The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion element ... Full text Link to item Cite

How does HIV env structure informs vaccine design?

Journal Article Microscopy and Microanalysis · January 1, 2020 Full text Cite

Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.

Journal Article Science · December 6, 2019 INTRODUCTION: A major goal of HIV-1 vaccine development is the design of immunogens that induce broadly neutralizing antibodies (bnAbs). However, vaccination of humans has not resulted in the induction of affinity-matured and potent HIV-1 bnAbs. To devise ... Full text Link to item Cite

Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.

Journal Article PLoS Pathog · September 2019 The CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein is susceptible to multiple lineages of broadly neutralizing antibodies (bnAbs) that are attractive to elicit with vaccines. The CH235 lineage (VH1-46) of CD4bs bnAbs is particularly attractive ... Full text Link to item Cite

Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.

Journal Article Nat Commun · February 8, 2019 Somatic mutations within antibody variable and framework regions (FWR) can alter thermostability and structural flexibility, but their impact on functional potency is unclear. Here we study thermostability and use molecular dynamics (MD) simulations to ass ... Full text Link to item Cite

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.

Journal Article Immunity · December 18, 2018 Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glyca ... Full text Link to item Cite

Domain Organization in the 54-kDa Subunit of the Chloroplast Signal Recognition Particle.

Journal Article Biophys J · September 20, 2016 Chloroplast signal recognition particle (cpSRP) is a heterodimer composed of an evolutionarily conserved 54-kDa GTPase (cpSRP54) and a unique 43-kDa subunit (cpSRP43) responsible for delivering light-harvesting chlorophyll binding protein to the thylakoid ... Full text Link to item Cite

Intrinsic GTP hydrolysis is observed for a switch 1 variant of Cdc42 in the presence of a specific GTPase inhibitor.

Journal Article Small GTPases · 2016 The Ras-related protein Cell division cycle 42 (Cdc42) is important in cell-signaling processes. Protein interactions involving Cdc42 occur primarily in flexible "Switch" regions that help regulate effector binding. We studied the kinetics of intrinsic GTP ... Full text Link to item Cite

Regulation of Structural Dynamics within a Signal Recognition Particle Promotes Binding of Protein Targeting Substrates.

Journal Article J Biol Chem · June 19, 2015 Protein targeting is critical in all living organisms and involves a signal recognition particle (SRP), an SRP receptor, and a translocase. In co-translational targeting, interactions among these proteins are mediated by the ribosome. In chloroplasts, the ... Full text Link to item Cite