Scholars@Duke
Priyamvada Acharya

Priyamvada Acharya

Professor in Surgery
Surgery, Surgical Sciences
priyamvada.acharya@duke.edu
DUMC Box 103020, Durham, NC 27710
10 Circuit Drive, Room 101, Research Park II, Durham, NC 27710

Selected Publications

Acquisition of quaternary trimer interaction as a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody.

Journal Article Structure · August 7, 2025 Although most broadly neutralizing antibodies (bNAbs) specific for the CD4-binding site (CD4-BS) of HIV-1 interact with a single gp120 protomer, a few mimic the quaternary binding mode of CD4, making contact with a second protomer through elongated heavy c ... Full text Link to item Cite

Design of SARS-CoV-2 RBD immunogens to focus immune responses toward conserved coronavirus epitopes.

Journal Article J Virol · July 22, 2025 SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach toward developing superior, variant-proof vaccines is to engineer immunogens that preferentially elicit an ... Full text Link to item Cite

Nonstabilized SARS-CoV-2 spike mRNA vaccination induces broadly neutralizing antibodies in nonhuman primates.

Journal Article Sci Transl Med · June 11, 2025 Immunization with messenger RNA (mRNA) or viral vectors encoding spike protein with diproline substitutions (S-2P) were shown to provide protective immunity, curbing the COVID-19 pandemic. However, in light of the emergence of severe acute respiratory synd ... Full text Link to item Cite

Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening.

Journal Article Nat Commun · May 17, 2025 The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminus of the envelope (Env) gp41 subunit. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41. The gp120/gp41 heterodimer ass ... Full text Link to item Cite

Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

Journal Article Mucosal Immunol · April 2025 Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic ... Full text Link to item Cite

An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.

Journal Article Sci Transl Med · January 8, 2025 Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Becaus ... Full text Link to item Cite

Fluorescent and bioluminescent bovine H5N1 influenza viruses for evaluation of antiviral interventions.

Journal Article J Virol · November 19, 2024 In early 2024, a clade 2.3.4.4b high pathogenic H5N1 avian influenza virus was detected in dairy cows and humans in the United States. Since then, it has spread to herds in at least 13 states and caused symptomatic disease in at least fifteen people. To fa ... Full text Link to item Cite

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

Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.

Journal Article PLoS Pathog · September 2024 Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape m ... Full text Link to item Cite

Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.

Journal Article Nat Commun · August 26, 2024 HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target f ... Full text Link to item Cite

Prying the lid open: Atomic-level insights on sialoglycan-TMPRSS2 coordination in HKU1 entry.

Journal Article Cell · August 8, 2024 The pre-fusion coronavirus HKU1 spike binds host sialoglycans and proteinaceous receptor TMPRSS2 for cell entry. In this issue of Cell, three papers by Fernández et al., McCallum et al., and Wang et al. provide structural information on HKU1 spike interact ... 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

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

Journal Article Cell · June 6, 2024 A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposom ... 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

Structural Studies of Henipavirus Glycoproteins.

Journal Article Viruses · January 27, 2024 Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses rely on two surface glycoproteins, known as the attachment and fusion proteins, to facilit ... 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

Cryo-electron microscopy in the study of virus entry and infection.

Journal Article Front Mol Biosci · 2024 Viruses have been responsible for many epidemics and pandemics that have impacted human life globally. The COVID-19 pandemic highlighted both our vulnerability to viral outbreaks, as well as the mobilization of the scientific community to come together to ... 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

Evolution of the SARS-CoV-2 Omicron spike.

Journal Article Cell Rep · December 26, 2023 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. The Omicron spike (S) protein accumulated an unprecedented nu ... Full text Link to item Cite

Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

Journal Article bioRxiv · December 19, 2023 Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits ne ... Full text Link to item Cite

Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted / founder sensitivity to broadly neutralizing antibodies.

Journal Article bioRxiv · December 5, 2023 HIV-1 envelope glycoproteins (Envs) mediate viral entry and are the sole target of neutralizing antibodies. Envs of most primary HIV-1 strains exist in a closed conformation and occasionally sample more open states. Thus, current knowledge guides immunogen ... Full text Link to item Cite

Structures of Langya Virus Fusion Protein Ectodomain in Pre- and Postfusion Conformation.

Journal Article J Virol · June 29, 2023 Langya virus (LayV) is a paramyxovirus in the Henipavirus genus, closely related to the deadly Nipah (NiV) and Hendra (HeV) viruses, that was identified in August 2022 through disease surveillance following animal exposure in eastern China. Paramyxoviruses ... Full text Link to item Cite

Microsecond dynamics control the HIV-1 envelope conformation.

Journal Article bioRxiv · May 18, 2023 The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although significant progress has been made in understanding the structures of various Env conformations and transition inte ... 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

Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

Journal Article Cell Rep · February 28, 2023 Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, ... Full text Link to item Cite

Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield.

Journal Article J Virol · January 31, 2023 The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expr ... 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

Human Immunodeficiency Virus Vaccines

Chapter · January 1, 2023 HIV-1 vaccine development is a critical global health priority. The reasons why we do not have an HIV-1 vaccine as yet are many, including a dense envelop glycan shield, rare neutralizing B cell precursors, the need for improbable neutralizing antibody mut ... Full text Cite

Transient transfection and purification of SARS-CoV-2 spike protein from mammalian cells.

Journal Article STAR Protoc · September 16, 2022 SARS-CoV-2 spike (S) protein ectodomain purification can be challenging, with engineered and natural variations often resulting in lower yields. Here, we present a detailed transfection and purification protocol for the SARS-CoV-2 S ectodomain. We describe ... Full text Link to item Cite

Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.

Journal Article Sci Transl Med · September 7, 2022 A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulat ... Full text Open Access 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

SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment.

Journal Article Annu Rev Med · January 27, 2022 Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, SARS-CoV-2 neutralizing antibodies have been developed for prev ... Full text Link to item Cite

A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.

Journal Article Sci Transl Med · January 26, 2022 Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly ef ... Full text Link to item Cite

Sequence and functional characterization of a public HIV-specific antibody clonotype.

Journal Article iScience · January 21, 2022 Public antibody clonotypes shared among multiple individuals have been identified for several pathogens. However, little is known about the determinants of antibody "publicness". Here, we characterize the sequence and functional properties of antibodies fr ... Full text Link to item Cite

How to train your antibody to fight malaria.

Journal Article Immunity · December 14, 2021 The Plasmodium falciparum circumsporozoite protein (PfCSP) is targeted by neutralizing antibodies and is a focus of malaria vaccine development. In this issue of Immunity, Kratochvil et al. (2021) combine vaccination and bioinformatics strategies to develo ... 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

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

Journal Article Cell · August 5, 2021 SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SA ... Full text Open Access Link to item Cite

SnapShot: SARS-CoV-2 antibodies.

Journal Article Cell Host Microbe · July 14, 2021 Full text Link to item Cite

Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions.

Journal Article Cell Rep Med · June 15, 2021 The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample ... Full text Link to item Cite

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Journal Article Nature · June 2021 Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and ... Full text Open Access 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

Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells.

Journal Article Cell Rep · May 25, 2021 Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we profile the repertoire of human leukocyte antigen class II (HLA-II)-bound pept ... Full text Open Access Link to item Cite

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice.

Journal Article bioRxiv · April 28, 2021 SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid preventi ... Full text Link to item Cite

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

Journal Article bioRxiv · March 15, 2021 UNLABELLED: New SARS-CoV-2 variants that have accumulated multiple mutations in the spike (S) glycoprotein enable increased transmission and resistance to neutralizing antibodies. Here, we study the antigenic and structural impacts of the S protein mutatio ... Full text Link to item Cite

The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

Journal Article bioRxiv · February 18, 2021 SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of S ... Full text Open Access Link to item Cite

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys.

Journal Article bioRxiv · February 17, 2021 Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circul ... Full text Open Access 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 Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

Journal Article Cell Host Microbe · January 13, 2021 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralizat ... 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

Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers.

Journal Article Front Immunol · 2021 Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset of HIV-1 infected individuals. Despite being traditionally associated with patients with high viral loads, bNAbs have also been obse ... Full text Link to item Cite

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

Journal Article bioRxiv · October 13, 2020 The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its Receptor Binding Domain in two conformations: receptor-accessible "up" or receptor-inaccessible "down" conformations. Here, we report that the commonly used s ... Full text Link to item Cite

D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction.

Journal Article bioRxiv · October 12, 2020 The SARS-CoV-2 spike (S) protein is the target of vaccine design efforts to end the COVID-19 pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic, and are now the dominant form worl ... 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

Glycans on the SARS-CoV-2 Spike Control the Receptor Binding Domain Conformation.

Journal Article bioRxiv · June 30, 2020 The glycan shield of the beta-coronavirus (β-CoV) Spike (S) glycoprotein provides protection from host immune responses, acting as a steric block to potentially neutralizing antibody responses. The conformationally dynamic S-protein is the primary immunoge ... Full text Link to item Cite

Pandemic Preparedness: Developing Vaccines and Therapeutic Antibodies For COVID-19.

Journal Article Cell · June 25, 2020 The SARS-CoV-2 pandemic that causes COVID-19 respiratory syndrome has caused global public health and economic crises, necessitating rapid development of vaccines and therapeutic countermeasures. The world-wide response to the COVID-19 pandemic has been un ... Full text Link to item Cite

Controlling the SARS-CoV-2 Spike Glycoprotein Conformation.

Journal Article bioRxiv · May 18, 2020 The coronavirus (CoV) viral host cell fusion spike (S) protein 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 moving target ... 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

High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity.

Journal Article Cell · December 12, 2019 B cell receptor (BCR) sequencing is a powerful tool for interrogating immune responses to infection and vaccination, but it provides limited information about the antigen specificity of the sequenced BCRs. Here, we present LIBRA-seq (linking B cell recepto ... Full text Link to item 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

Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.

Journal Article Cell · July 25, 2019 The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neut ... Full text Link to item Cite

Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition.

Journal Article Structure · January 2, 2019 Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand this recognition and its implications, we analyzed 206 an ... Full text Link to item Cite

Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1-4.

Journal Article Proc Natl Acad Sci U S A · November 27, 2018 Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. To obtain a vaccine effective against all four ... Full text Link to item Cite

Germline-targeting and Reverse Engineering to Elicit CH235.12 Lineage bNAbs

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Macaque SHIV Induction of 2G12-like Broadly Neutralizing Antibodies

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV.

Journal Article PLoS Pathog · July 2018 Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutrali ... Full text Link to item Cite

Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.

Journal Article Nat Med · June 2018 A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component o ... Full text Link to item Cite

Routine single particle CryoEM sample and grid characterization by tomography.

Journal Article Elife · May 29, 2018 Single particle cryo-electron microscopy (cryoEM) is often performed under the assumption that particles are not adsorbed to the air-water interfaces and in thin, vitreous ice. In this study, we performed fiducial-less tomography on over 50 different cryoE ... Full text Link to item Cite

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens.

Journal Article ACS Infect Dis · May 11, 2018 Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that ... Full text Link to item Cite

Spotiton: New features and applications.

Journal Article J Struct Biol · May 2018 We present an update describing new features and applications of Spotiton, a novel instrument for vitrifying samples for cryoEM. We have used Spotiton to prepare several test specimens that can be reconstructed using routine single particle analysis to ∼3  ... Full text Link to item Cite

Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity.

Journal Article J Virol · May 15, 2017 The HIV-1 envelope (Env) trimer is a target for vaccine design as well as a conformational machine that facilitates virus entry by transitioning between prefusion-closed, CD4-bound, and coreceptor-bound conformations by transitioning into a postfusion stat ... Full text Link to item Cite

Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.

Journal Article Nat Struct Mol Biol · April 2017 Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of ... Full text Link to item Cite

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.

Journal Article Science · May 13, 2016 The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which tar ... Full text Link to item Cite

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Journal Article Cell · April 7, 2016 Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived a ... Full text Link to item Cite

Cocrystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1.

Journal Article J Virol · September 2015 UNLABELLED: Accumulating evidence indicates a role for Fc receptor (FcR)-mediated effector functions of antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), in prevention of human immunodeficiency virus type 1 (HIV-1) acquisition and ... Full text Link to item Cite

Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.

Journal Article Nat Struct Mol Biol · July 2015 As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed tr ... Full text Link to item Cite

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.

Journal Article Cell · June 4, 2015 The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site ... Full text Link to item Cite

HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.

Journal Article Expert Opin Ther Targets · June 2015 INTRODUCTION: The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principl ... Full text Link to item Cite

The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells.

Journal Article PLoS Pathog · May 2015 For nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells. Mechanistically, this Vpx activity was recently reported to involve the degradation of Sterile ... Full text Link to item Cite

Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.

Journal Article mBio · April 21, 2015 UNLABELLED: Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related ... Full text Open Access Link to item Cite

Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection.

Journal Article J Virol · November 2014 UNLABELLED: The RV144 vaccine trial implicated epitopes in the C1 region of gp120 (A32-like epitopes) as targets of potentially protective antibody-dependent cellular cytotoxicity (ADCC) responses. A32-like epitopes are highly immunogenic, as infected or v ... Full text Link to item Cite

Structure and immune recognition of trimeric pre-fusion HIV-1 Env.

Journal Article Nature · October 23, 2014 The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediat ... Full text Link to item Cite

Residue-level prediction of HIV-1 antibody epitopes based on neutralization of diverse viral strains.

Journal Article J Virol · September 2013 Delineation of antibody epitopes at the residue level is key to understanding antigen resistance mutations, designing epitope-specific probes for antibody isolation, and developing epitope-based vaccines. Ideally, epitope residues are determined in the con ... Full text Link to item Cite

Heavy chain-only IgG2b llama antibody effects near-pan HIV-1 neutralization by recognizing a CD4-induced epitope that includes elements of coreceptor- and CD4-binding sites.

Journal Article J Virol · September 2013 The conserved HIV-1 site of coreceptor binding is protected from antibody-directed neutralization by conformational and steric restrictions. While inaccessible to most human antibodies, the coreceptor site has been shown to be accessed by antibody fragment ... Full text Link to item Cite

Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies.

Journal Article Immunity · August 22, 2013 Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make el ... Full text Link to item Cite

Interfacial cavity filling to optimize CD4-mimetic miniprotein interactions with HIV-1 surface glycoprotein.

Journal Article J Med Chem · June 27, 2013 Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed ... Full text Link to item Cite

Structural basis for highly effective HIV-1 neutralization by CD4-mimetic miniproteins revealed by 1.5 Å cocrystal structure of gp120 and M48U1.

Journal Article Structure · June 4, 2013 The interface between the HIV-1 gp120 envelope glycoprotein and the CD4 receptor contains an unusual interfacial cavity, the "Phe43 cavity", which CD4-mimetic miniproteins with nonnatural extensions can potentially utilize to enhance their neutralization o ... Full text Link to item Cite

Peptides from second extracellular loop of C-C chemokine receptor type 5 (CCR5) inhibit diverse strains of HIV-1.

Journal Article J Biol Chem · April 27, 2012 To initiate HIV entry, the HIV envelope protein gp120 must engage its primary receptor CD4 and a coreceptor CCR5 or CXCR4. In the absence of a high resolution structure of a gp120-coreceptor complex, biochemical studies of CCR5 have revealed the importance ... Full text Link to item Cite

Structure-based identification and neutralization mechanism of tyrosine sulfate mimetics that inhibit HIV-1 entry.

Journal Article ACS Chem Biol · October 21, 2011 Tyrosine sulfate-mediated interactions play an important role in HIV-1 entry. After engaging the CD4 receptor at the cell surface, the HIV-1 gp120 glycoprotein binds to the CCR5 co-receptor via an interaction that requires two tyrosine sulfates, at positio ... Full text Link to item Cite

Tyrosine-sulfate isosteres of CCR5 N-terminus as tools for studying HIV-1 entry.

Journal Article Bioorg Med Chem · December 1, 2008 The HIV-1 co-receptor CCR5 possesses sulfo-tyrosine (TYS) residues at its N-terminus (Nt) that are required for binding HIV-1 gp120 and mediating viral entry. By using a 14-residue fragment of CCR5 Nt containing two TYS residues, we recently showed that CC ... Full text Link to item Cite

Structural basis for the remarkable stability of Bacillus subtilis lipase (Lip A) at low pH.

Journal Article Biochim Biophys Acta · February 2008 Understanding the structural basis of altered properties of proteins due to changes in temperature or pH provides useful insights in designing proteins with improved stability. Here we report the basis for the pH-dependent thermostability of the Bacillus s ... Full text Link to item Cite

Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4.

Journal Article Science · September 28, 2007 The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic reson ... Full text Link to item Cite

The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes.

Journal Article J Mol Biol · March 31, 2006 Formylmethanofuran:tetrahydromethanopterin formyltransferase is an essential enzyme in the one-carbon metabolism of methanogenic and sulfate-reducing archaea and of methylotrophic bacteria. The enzyme, which is devoid of a prosthetic group, catalyzes the r ... Full text Link to item Cite

Multiplex-PCR-based recombination as a novel high-fidelity method for directed evolution.

Journal Article Chembiochem · June 2005 A new and convenient method for the in vitro recombination of single point mutations is presented. This method efficiently reduces the introduction of novel point mutations, which usually occur during recombination processes. A multiplex polymerase chain r ... Full text Link to item Cite

How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1.

Journal Article J Biol Chem · April 8, 2005 Tetrahydromethanopterin (H4 MPT) is a tetrahydrofolate analogue involved as a C1 carrier in the metabolism of various groups of microorganisms. How H4MPT is bound to the respective C1 unit converting enzymes remained elusive. We describe here the structure ... Full text Link to item Cite

Structural basis of selection and thermostability of laboratory evolved Bacillus subtilis lipase.

Journal Article J Mol Biol · August 27, 2004 Variation in gene sequences generated by directed evolution approaches often does not assure a minimalist design for obtaining a desired property in proteins. While screening for enhanced thermostability, structural information was utilized in selecting mu ... Full text Link to item Cite

Crystallization and preliminary X-ray crystallographic investigations on several thermostable forms of a Bacillus subtilis lipase.

Journal Article Acta Crystallogr D Biol Crystallogr · January 2004 Bacillus subtilis lipase loses activity above pH 10.5 and below pH 6.0. However, at low pH, i.e. below pH 5.0, the lipase acquires remarkable thermostability. Activity was unaltered for 2 h at 323 K at pH 4.0-5.0, although at pH values above 7.0 the activi ... Full text Link to item Cite

Stability studies on a lipase from Bacillus subtilis in guanidinium chloride.

Journal Article J Protein Chem · January 2003 Lipase from Bacillus subtilis is a "lidless" lipase that does not show interfacial activation. Due to exposure of the active site to solvent, the lipase tends to aggregate. We have investigated the solution properties and unfolding of the lipase in guanidi ... Full text Link to item Cite

Anomalous ester hydrolysis in mixed micelles of p-nitrophenyloleate-triton X-100 in the presence of guanidinium chloride: Implications in lipase assays

Journal Article Langmuir · April 16, 2002 Substrates insoluble in water are often presented to enzymes in micellized form. We observed anomalous increases in activities of lipases, with p-nitrophenyl oleate (PNPO)-Triton X-100 mixed micelles as the substrate system, in the presence of the protein ... Full text Cite