Scholars@Duke
Daniel Wrapp

Daniel Wrapp

Assistant Professor in Medicine
Medicine, Duke Human Vaccine Institute
daniel.wrapp@duke.edu
DUMC 103020, Durham, NC 27710
Rm 3072B, MSRBII, Durham, NC 27710

Selected Publications

A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain.

Journal Article Commun Biol · December 31, 2025 HCoV-229E is an endemic Alphacoronavirus that typically causes common cold-like disease in most healthy adults, but can also cause severe respiratory disease in the very young and the elderly. Although the virus was discovered over sixty years ago and unde ... Full text Link to item Cite

Discrimination of primary and chronic cytomegalovirus infection based on humoral immune profiles in pregnancy.

Journal Article J Clin Invest · October 15, 2024 BACKGROUNDMost humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently present ... Full text Link to item Cite

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Journal Article Nat Commun · November 30, 2023 Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815 ... Full text Link to item Cite

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope.

Journal Article J Virol · October 31, 2023 Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants, infecting all children by age 5. RSV also causes substantial morbidity and mortality in older adults, and a vaccine for older adults based on a prefusion-stab ... Full text Link to item Cite

Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera.

Journal Article Nat Commun · October 4, 2023 Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable virus ... Full text Link to item Cite

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

Journal Article mBio · February 28, 2023 HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in ... 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

A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus.

Journal Article PLoS Pathog · January 2023 Cytomegalovirus (CMV) is a leading cause of infant hearing loss and neurodevelopmental delay, but there are no clinically licensed vaccines to prevent infection, in part due to challenges eliciting neutralizing antibodies. One of the most well-studied targ ... Full text Link to item Cite

A novel humanized Chi3l1 blocking antibody attenuates acetaminophen-induced liver injury in mice

Journal Article Antibody Therapeutics · January 1, 2023 Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l ... Full text Cite

Efficient discovery of SARS-CoV-2-neutralizing antibodies via B cell receptor sequencing and ligand blocking.

Journal Article Nat Biotechnol · August 2022 Although several monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved for coronavirus disease 2019 (COVID-19) therapy, development was generally inefficient, with lead generation often requi ... Full text Link to item Cite

Structural rearrangements allow nucleic acid discrimination by type I-D Cascade.

Journal Article Nat Commun · May 20, 2022 CRISPR-Cas systems are adaptive immune systems that protect prokaryotes from foreign nucleic acids, such as bacteriophages. Two of the most prevalent CRISPR-Cas systems include type I and type III. Interestingly, the type I-D interference proteins contain ... Full text Link to item Cite

Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies.

Journal Article Sci Adv · March 11, 2022 Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting w ... Full text Link to item Cite

Expression and characterization of SARS-CoV-2 spike proteins.

Journal Article Nat Protoc · November 2021 The severe acute respiratory syndrome coronavirus 2 spike protein is a critical component of coronavirus disease 2019 vaccines and diagnostics and is also a therapeutic target. However, the spike protein is difficult to produce recombinantly because it is ... Full text Link to item Cite

A Combination of Receptor-Binding Domain and N-Terminal Domain Neutralizing Antibodies Limits the Generation of SARS-CoV-2 Spike Neutralization-Escape Mutants.

Journal Article mBio · October 26, 2021 Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection by targeting the receptor-binding domain (RBD) of the spike (S) protein. Variants of concern (VOC) carrying mutations in th ... Full text Link to item Cite

Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition.

Journal Article Cell Rep · October 5, 2021 The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID ... 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

The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.

Journal Article Sci Transl Med · May 12, 2021 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campai ... Full text Link to item Cite

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.

Journal Article Immunity · April 13, 2021 An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adult ... Full text Link to item Cite

Prolonged evolution of the human B cell response to SARS-CoV-2 infection.

Journal Article Sci Immunol · February 23, 2021 A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe CO ... Full text Link to item Cite

Local computational methods to improve the interpretability and analysis of cryo-EM maps.

Journal Article Nat Commun · February 23, 2021 Cryo-electron microscopy (cryo-EM) maps usually show heterogeneous distributions of B-factors and electron density occupancies and are typically B-factor sharpened to improve their contrast and interpretability at high-resolutions. However, 'over-sharpenin ... Full text Link to item Cite

Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.

Journal Article Science · February 19, 2021 The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-Co ... Full text Link to item Cite

Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape.

Journal Article Nat Commun · January 20, 2021 Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape remain unclear. We compared the critical residues in the rec ... Full text Link to item Cite

Local methods to improve cryo-electron microcopy maps

Conference Optics Infobase Conference Papers · January 1, 2021 Cryo-electron microscopy (cryo-EM) has become a powerful technique for protein structure determination. However, there are still important issues to be addressed, such as, robust sharpening or local B-factors estimations. To address these issues, we presen ... Cite

Structural basis for assembly of non-canonical small subunits into type I-C Cascade.

Journal Article Nat Commun · November 23, 2020 Bacteria and archaea employ CRISPR (clustered, regularly, interspaced, short palindromic repeats)-Cas (CRISPR-associated) systems as a type of adaptive immunity to target and degrade foreign nucleic acids. While a myriad of CRISPR-Cas systems have been ide ... Full text Link to item Cite

Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures

Journal Article Iucrj · November 1, 2020 Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involv ... Full text Cite

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.

Journal Article Nature · October 2020 A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike protei ... Full text Link to item Cite

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes.

Journal Article Science · September 18, 2020 The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 s ... Full text Link to item Cite

Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection.

Journal Article Virology · September 2020 Human cytomegalovirus (HCMV) is the most common congenital infection. A glycoprotein B (gB) subunit vaccine (gB/MF59) is the most efficacious clinically tested to date, having achieved 50% protection against primary infection of HCMV-seronegative women. We ... Full text Link to item Cite

Broad neutralization of SARS-related viruses by human monoclonal antibodies.

Journal Article Science · August 7, 2020 Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respira ... Full text Link to item Cite

Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step.

Journal Article PLoS Pathog · August 2020 Human cytomegalovirus (HCMV) is one of the main causative agents of congenital viral infection in neonates. HCMV infection also causes serious morbidity and mortality among organ transplant patients. Glycoprotein B (gB) is a major target for HCMV neutraliz ... Full text Link to item Cite

Site-specific glycan analysis of the SARS-CoV-2 spike.

Journal Article Science · July 17, 2020 The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the p ... Full text Link to item Cite

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.

Journal Article Cell · May 28, 2020 Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. He ... Full text Link to item Cite

Immunogenicity of a DNA vaccine candidate for COVID-19.

Journal Article Nat Commun · May 20, 2020 The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a syn ... Full text Link to item Cite

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.

Journal Article Science · March 13, 2020 The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To ... Full text Link to item Cite

The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation.

Journal Article J Virol · December 1, 2019 Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that has a significant agricultural and economic impact due to the high mortality rate associated with infection of neonatal piglets. Like other coronaviruses, PEDV makes use of a large, trimeri ... Full text Link to item Cite

Iterative screen optimization maximizes the efficiency of macromolecular crystallization.

Journal Article Acta Crystallogr F Struct Biol Commun · February 1, 2019 Advances in X-ray crystallography have streamlined the process of determining high-resolution three-dimensional macromolecular structures. However, a rate-limiting step in this process continues to be the generation of crystals that are of sufficient size ... Full text Link to item Cite

Publisher Correction: Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis.

Journal Article Sci Rep · December 10, 2018 A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ... Full text Link to item Cite

Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis.

Journal Article Sci Rep · October 24, 2018 Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fu ... Full text Link to item Cite

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation.

Journal Article Immunity · February 20, 2018 Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilita ... Full text Link to item Cite

Corrigendum: Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

Journal Article Nat Commun · November 29, 2017 This corrects the article DOI: 10.1038/ncomms14158. ... Full text Link to item Cite

Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen.

Journal Article Proc Natl Acad Sci U S A · August 29, 2017 Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MER ... Full text Link to item Cite

A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants.

Journal Article Sci Transl Med · May 3, 2017 Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited ... Full text Link to item Cite

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

Journal Article Nat Commun · February 13, 2017 Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conforma ... Full text Link to item Cite

General Assessment of Humoral Activity in Healthy Humans.

Journal Article Mol Cell Proteomics · May 2016 The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous h ... Full text Link to item Cite