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Influence of glycosylation on the immunogenicity and antigenicity of viral immunogens

BIOTECHNOLOGY ADVANCES (2024)

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Article Biochemistry & Molecular Biology

Variations within the Glycan Shield of SARS-CoV-2 Impact Viral Spike Dynamics

Maddy L. Newby et al.

Summary: The emergence of SARS-CoV-2 variants affects the effectiveness of existing immunity. Understanding the structure of the viral spike helps determine the impact of mutations on the antigenic surface. One type of mutation affects glycosylation attachment sites, which can influence the antigenic structure beyond the immediate attachment site. This study compares the glycosylation of different variants and investigates the effects of specific glycan sites on the spike protein.

JOURNAL OF MOLECULAR BIOLOGY (2023)

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Article Multidisciplinary Sciences

Visualization of translation and protein biogenesis at the ER membrane

Max Gemmer et al.

Summary: This study uses cryo-electron tomography and molecular modeling to capture snapshots of mRNA translation and protein maturation at the ER membrane. They identify a high abundance pre-translocation intermediate with eukaryotic elongation factor 1a (eEF1a) and observe distinct polysomes binding to different ER translocons specialized in protein synthesis. They also obtain near-complete atomic models of ER translocon variants, revealing specific interactions and stoichiometric cofactors associated with protein isomerases.

NATURE (2023)

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Review Immunology

Cell-Based Manufacturing Technology Increases Antigenic Match of Influenza Vaccine and Results in Improved Effectiveness

Steven Rockman et al.

Summary: To ensure effective protection, vaccination must match the circulating strains of infectious diseases. Random mutations during nucleic acid replication can affect the effectiveness of traditional influenza vaccines produced in chicken eggs. Using Madin-Darby canine kidney (MDCK) cell lines for vaccine production helps avoid these egg-adaptive mutations. Cell-based vaccines, such as Flucelvax Quadrivalent, demonstrate no mutations in the antigenic sites of hemagglutinin or neuraminidase, ensuring the vaccine matches recommended strains. Real world effectiveness studies support the use of cell-based influenza vaccines.

VACCINES (2023)

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Article Biochemical Research Methods

Analysis of the N-glycosylation profiles of the spike proteins from the Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2

Dongxia Wang et al.

Summary: N-Glycosylation plays a crucial role in the structure and function of membrane and secreted proteins. This study examined the N-glycosylation profiles of different SARS-CoV-2 variants and found that amino acid substitutions and deletions between variants affect the abundance and type of glycans on the spike protein. Multiple digestion methods were applied to improve the identification and quantification of glycopeptides. The detailed analysis of glycosylation in SARS-CoV-2 variants provides valuable insights for understanding viral protein structure and function, and for the development of effective vaccines and therapeutics.

ANALYTICAL AND BIOANALYTICAL CHEMISTRY (2023)

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Article Multidisciplinary Sciences

Site specific N- and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concern

Asif Shajahan et al.

Summary: This study compares the glycosylation profiles of different variants of the SARS-CoV-2 virus and finds that the glycosylation sites on the spike protein remain highly conserved despite mutations. The newly emerged variants show changes in glycosylation patterns that may be related to their infectivity.

SCIENTIFIC REPORTS (2023)

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Review Biotechnology & Applied Microbiology

Understanding glycosylation: Regulation through the metabolic flux of precursor pathways

Aert F. Scheper et al.

Summary: Glycosylation is a process of modifying proteins and lipids with complex carbohydrates called glycans. It is not template-driven like genetic transcription or protein translation, but rather dynamically regulated by metabolic flux. This review provides an overview of the metabolic pathways involved in glycan synthesis and explains the dysregulation of glycosylation in inflammation. The resulting inflammatory hyperglycosylation acts as a glycosignature of disease, and studies on metabolic inhibitors targeting critical enzymes have identified potential glycotherapeutic approaches to inflammation.

BIOTECHNOLOGY ADVANCES (2023)

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Article Multidisciplinary Sciences

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Adam J. Ronk et al.

Summary: The study presents an mRNA-based Lassa virus vaccine that provides protection against lethal infection in a guinea pig model without the need for neutralizing antibodies. Vaccination induced strong binding antibody responses and demonstrated the potential of mRNA vaccines as a platform against Lassa virus.

NATURE COMMUNICATIONS (2023)

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Review Immunology

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies

Barton F. Haynes et al.

Summary: The development of a safe and effective HIV-1 vaccine has been a challenging task due to the genetic diversity of the virus and its mechanisms of immune evasion. This article discusses strategies for inducing potent and broad HIV-1 neutralizing antibodies and outlines the necessary steps for achieving ultimate success.

NATURE REVIEWS IMMUNOLOGY (2023)

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Article Biochemistry & Molecular Biology

Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic

Himanshi Chawla et al.

Summary: The glycosylation of the expression-enhanced spike protein resembles that of an earlier version but with some differences; both HexaPro and 2P proteins are able to detect immune responses in infected individuals; variations in glycan processing do not impact serological assessments being performed globally.

JOURNAL OF MOLECULAR BIOLOGY (2022)

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Article Virology

N-Glycolylneuraminic Acid Binding of Avian and Equine H7 Influenza A Viruses

Cindy M. Spruit et al.

Summary: Influenza A viruses cause millions of severe illnesses and deaths each year. This study investigates the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc.

JOURNAL OF VIROLOGY (2022)

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Article Medicine, General & Internal

Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

Lisa M. Dunkle et al.

Summary: The NVX-CoV2373 vaccine has shown to be safe and highly effective in preventing Covid-19, with a vaccine efficacy of 90.4% against reverse-transcriptase-polymerase-chain-reaction-confirmed cases and 100% efficacy against moderate-to-severe disease. The vaccine also demonstrated high efficacy against various variants of the virus.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Cell Biology

Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens

Benjamin J. Read et al.

Summary: Mannose binding lectin (MBL) in nanoparticle vaccines promotes immune responses by increasing antigen accumulation in lymph nodes and antigen-specific germinal center (GC) responses. The findings provide a framework for optimizing vaccine efficacy.

CELL REPORTS (2022)

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Article Biochemistry & Molecular Biology

Glycosylation as a key parameter in the design of nucleic acid vaccines

Ahmet Ozdilek et al.

Summary: It is crucial to generate vaccine antigens that are immunologically similar to native antigens. This review explores the potential impact of host protein glycosylation on the immune responses generated by nucleic acid vaccines against bacterial and viral pathogens.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2022)

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Letter Medicine, General & Internal

Host-targeting oral antiviral drugs to prevent pandemics

Raymond A. Dwek et al.

LANCET (2022)

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Article Multidisciplinary Sciences

COVID-19 therapeutics: Challenges and directions for the future

Philip C. Robinson et al.

Summary: The emergence of SARS-CoV-2 and the resulting COVID-19 pandemic have had a significant impact on global society. While substantial investment in life sciences has led to rapid advancements in viral characterization, testing, and the development of highly effective vaccines, drug treatments for COVID-19 have been limited. Innovative approaches in clinical trials and repurposing existing drugs have saved lives, but there is still a need for further development of therapeutics. It is important to address the challenges and unmet needs in order to prepare for future pandemics and ensure the cost-effective development and equitable distribution of new therapeutics.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Cell Biology

Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models

Han-Yi Huang et al.

Summary: This study revealed that glycosylation of the viral surface spike (S) protein affects viral infectivity. Trimmed N-glycans on the S protein showed stronger immune responses and better protection in transgenic mice. Furthermore, a broadly neutralizing monoclonal antibody with subpicomolar potency was discovered. These findings suggest that removing glycan shields could be an effective approach for developing a broadly protective vaccine.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Glycans in HIV-1 vaccine design - engaging the shield

Lachlan P. Deimel et al.

Summary: The article discusses the role of glycans in protein evasion and as antibody targets, and explores potential approaches to design HIV-1 vaccines using glycan targeting.

TRENDS IN MICROBIOLOGY (2022)

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Article Cell Biology

Highly mutated antibodies capable of neutralizing N276 glycan-deficient HIV after a single immunization with an Env trimer

Jeong Hyun Lee et al.

Summary: Inducing broadly neutralizing antibodies against HIV is challenging, but this study shows that using germline-targeting immunogens can lead to the accumulation of high-affinity antibodies with potent neutralization after a single immunization.

CELL REPORTS (2022)

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Article Multidisciplinary Sciences

Applying transcriptomics to study glycosylation at the cell type level

Leo Alexander Dworkin et al.

Summary: This study investigates the state of glycosylation machinery and metabolic network in a single cell using single cell RNA-seq data. The research reveals that most of the protein and lipid oligosaccharide scaffolds are produced by enzymes with limited transcriptional regulation among cells. Key enzymes within different glycosylation pathways are predicted to be highly transcriptionally regulated.

ISCIENCE (2022)

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Article Multidisciplinary Sciences

Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate

Kwinten Sliepen et al.

Summary: This study describes the generation of recombinant soluble E1E2 immunogens, which are displayed on nanoparticles and induce potent neutralizing antibody responses. Furthermore, mosaic nanoparticles displaying multiple different E2E1 immunogens significantly improve neutralization.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

A naturally arising broad and potent CD4-binding site antibody with low somatic mutation

Christopher O. Barnes et al.

Summary: This study describes a less mutated VRC01-class antibody with comparable breadth and potency. The crystal structure analysis reveals conserved contacts at the CD4-binding site similar to other VRC01-class antibodies. Moderately mutated CD4bs bNAbs offer a simpler blueprint for antibody induction by a vaccine.

SCIENCE ADVANCES (2022)

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Article Biology

Glycan shield of the ebolavirus envelope glycoprotein GP

Weiwei Peng et al.

Summary: This study utilized glycoproteomics to investigate the glycosylation patterns of the ebolavirus GP protein. The results revealed multiple forms of glycosylation at different sites of GP, which play crucial roles in host cell attachment, GP stability, fusion activity, and resistance against neutralizing antibodies. The findings contribute to a better understanding of the mechanisms behind the interactions between ebolavirus GP and antibodies.

COMMUNICATIONS BIOLOGY (2022)

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Article Immunology

Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors

Jordan R. Willis et al.

Summary: Researchers have identified two important antibodies for HIV vaccine development through deep sequencing of human antibody heavy-chain sequences.

IMMUNITY (2022)

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Article Multidisciplinary Sciences

Structure of the hepatitis C virus E1E2 glycoprotein complex

Alba Torrents de la Peña et al.

SCIENCE (2022)

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Review Virology

Influence of Host Sialic Acid Receptors Structure on the Host Specificity of Influenza Viruses

Chuankuo Zhao et al.

Summary: Influenza viruses utilize sialic acid receptors to invade host cells, and factors such as sialic acid variants, glycan structural differences, and sulfation/fucosylation affect the specificity of viral host binding. Understanding these factors can contribute to the investigation of cross-species transmission of influenza viruses and the development of antiviral drugs.

VIRUSES-BASEL (2022)

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Article Multidisciplinary Sciences

HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design

Kim-Marie A. Dam et al.

Summary: This study reveals the critical interactions between the BG24 antibody and HIV-1 Env, as well as the structural features of antibody adaptability. These findings provide guidance for designing immunogens targeting CD4bs.

NATURE COMMUNICATIONS (2022)

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Article Microbiology

Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection

Philip J. M. Brouwer et al.

Summary: The use of two-component protein nanoparticles to stabilize the Lassa virus glycoprotein complex (GPC) trimers has shown promising results in vaccine development, inducing potent immune responses and protection against the lethal Lassa virus challenge in animal models.

CELL HOST & MICROBE (2022)

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Article Medicine, General & Internal

Safety and immunogenicity of an HIV-1 prefusion- stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label , randomized, dose-escalation, phase 1 clinical trial

Katherine Houser et al.

Summary: The HIV-1 vaccine Trimer 4571 adjuvanted with alum was found to be safe, well-tolerated, and immunogenic in HIV-negative adults. The trial demonstrated mild to moderate reactogenicity, with the most common side effects being injection site tenderness and myalgia. The vaccine induced seropositivity in a significant portion of participants, with most developing binding antibodies focused on the glycan-free trimer base and neutralizing antibody activity primarily observed in the 500 mcg dose groups.

ECLINICALMEDICINE (2022)

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Article Biochemistry & Molecular Biology

UCSF ChimeraX: Structure visualization for researchers, educators, and developers

Eric F. Pettersen et al.

Summary: UCSF ChimeraX is a powerful visualization program with enhanced performance and graphics, offering new tools and analysis features, support for various areas like virtual reality, and improved ease of use, along with an app store for researchers to contribute new tools.

PROTEIN SCIENCE (2021)

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Review Biochemistry & Molecular Biology

Influenza A Viruses: Understanding Human Host Determinants

Kevin Ciminski et al.

Summary: Emergent IAV strains from animal hosts typically have poor adaptation to humans and cannot establish sustained transmission. Despite frequent exposure to endemic IAV in animal populations, the number of pandemics in humans remains surprisingly low.

TRENDS IN MOLECULAR MEDICINE (2021)

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Article Chemistry, Analytical

Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints

Charles F. S. Eldrid et al.

Summary: Understanding the glycosylation of the SARS-CoV-2 envelope spike protein is crucial in determining the antigenic surface of this viral target. Different recombinant fragments of the S protein may exhibit varying glycosylation patterns. The quaternary protein architecture in matched expression systems has been shown to limit O-linked glycosylation of the spike protein.

ANALYTICAL CHEMISTRY (2021)

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Article Biochemical Research Methods

Altered N-linked glycosylation in endometrial cancer

Parul Mittal et al.

Summary: N-linked glycan MALDI MSI can differentiate between normal and cancerous endometrium, as well as endometrial cancer with lymph node metastasis from endometrial cancer without metastasis. This technique has the potential to aid in the identification and characterization of glycan alterations associated with cancer progression.

ANALYTICAL AND BIOANALYTICAL CHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Raffael Nachbagauer et al.

Summary: New influenza virus vaccines based on chimeric hemagglutinin have been found to induce a broad, strong, durable and functional immune response targeting the conserved stalk of the hemagglutinin protein. This suggests that these chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

NATURE MEDICINE (2021)

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Article Multidisciplinary Sciences

Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer

Johnathan D. Guest et al.

Summary: The variability of HCV poses a challenge for vaccine development, but a soluble form of E1E2 has been designed to elicit neutralizing antibodies in vivo and potentially optimize E1E2-based antigen production for future studies.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biochemistry & Molecular Biology

Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase

Carlos P. Modenutti et al.

Summary: This study presents crystal structures of Chaetomium thermophilum UGGT and molecular dynamics simulations showing conformational changes. The estimated Parodi limit of UGGT is around 70-80 angstroms based on the MD simulations, with relevance of this limit to UGGT activity in vivo suggested by distance distributions in glycoprotein crystal structures.

STRUCTURE (2021)

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Article Multidisciplinary Sciences

SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice

Jing-Hui Tian et al.

Summary: The study reports the development of a SARS-CoV-2 subunit vaccine candidate that contains full-length spike protein stabilized in its prefusion conformation, showing immunogenicity in mice and protection in baboons with Matrix-M adjuvanted vaccine, supporting ongoing phase 1/2 clinical evaluation of NVX-CoV2373 with Matrix-M (NCT04368988).

NATURE COMMUNICATIONS (2021)

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Review Microbiology

Virus vaccines: proteins prefer prolines

Rogier W. Sanders et al.

Summary: Most viral vaccines work by inducing neutralizing antibodies against the virus envelope or spike glycoproteins, which are engineered for stability and presentation of key epitopes to optimize vaccine performance. This technique emerged during HIV-1 Env vaccine development and has been widely applied to other viral vaccines, including SARS-CoV-2.

CELL HOST & MICROBE (2021)

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Article Virology

The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization

Anna Schorcht et al.

JOURNAL OF VIROLOGY (2021)

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Article Biochemical Research Methods

Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis

Rebeca Kawahara et al.

Summary: The study evaluated the performance of glycoproteomics software, identifying high-performance informatics strategies and recommending improvements for search solutions.

NATURE METHODS (2021)

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Article Microbiology

The C3/465 glycan hole cluster in BG505 HIV-1 envelope is the major neutralizing target involved in preventing mucosal SHIV infection

Tysheena P. Charles et al.

Summary: This study demonstrates that neutralizing antibodies primarily targeting an exposed region on the HIV-1 envelope trimer vaccine were associated with protection, which could be achieved by a single expanding antibody family.

PLOS PATHOGENS (2021)

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Article Immunology

Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

Philip J. M. Brouwer et al.

Summary: The study successfully induced 60-fold higher autologous Tier-2 neutralizing antibody titers by presenting 16055 clade C Tier-2 genotype SOSIP trimers on nanoparticles compared to the corresponding SOSIP trimers. Epitope mapping studies revealed that the presentation of 16055 SOSIP trimers on these nanoparticles focused antibody responses on an immunodominant apical epitope.

NPJ VACCINES (2021)

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Review Immunology

Protein engineering strategies for rational immunogen design

Timothy M. Caradonna et al.

Summary: Antibody immunodominance refers to the preferential elicitation of antibodies against specific epitopes on a complex protein antigen, causing limited success of traditional vaccination approaches for rapidly evolving pathogens. Protein engineering strategies can selectively alter patterns of immunodominance, focusing antibody responses toward broadly protective epitopes in pursuit of next-generation vaccines.

NPJ VACCINES (2021)

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Article Virology

Characterization of membrane topology and retention signal of pestiviral glycoprotein E1

Yu Mu et al.

JOURNAL OF VIROLOGY (2021)

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Article Biochemistry & Molecular Biology

Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19

Brian J. Ward et al.

Summary: This study reported the interim safety and immunogenicity data of a plant-produced COVID-19 vaccine candidate at Day 42. The results showed good tolerability of all formulations and induction of immune responses, supporting further evaluation of the vaccine candidate.

NATURE MEDICINE (2021)

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Article Medicine, General & Internal

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant

V. Shinde et al.

Summary: The NVX-CoV2373 vaccine showed efficacy in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Multidisciplinary Sciences

Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines

Linling He et al.

Summary: The study identifies mutations to improve GP stability and yield, designs two multilayered nanoparticle carriers, and demonstrates good immunogenicity of the modified GP on nanoparticles in mice and rabbits.

NATURE COMMUNICATIONS (2021)

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Article Cell Biology

Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike

Ronald Derking et al.

Summary: Artificial glycan holes can induce strain-specific neutralizing antibodies or non-neutralizing antibodies on recombinant Env-based vaccines. By replacing NxS with NxT, researchers have successfully increased the occupancy of most N-linked glycosylation sites to mimic native glycosylation and eliminate glycan holes.

CELL REPORTS (2021)

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Article Cell Biology

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

Robert Parker et al.

Summary: This study profiles the repertoire of HLA-DR-bound peptides presented by monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike protein. It identifies 209 unique peptide sequences mapping to various sites on the S protein, with substantial trimming of glycan residues observed on the bound peptides. The study also highlights the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identifies potential target peptides in S2 for cross-protective vaccine-elicited responses.

CELL REPORTS (2021)

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Article Cell Biology

Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies

Charles D. Murin et al.

Summary: This study identified antibodies targeting the glycan cap epitope on the ebolavirus glycoprotein with broad neutralizing activity, and revealed the structural features of these antibodies working in synergy with base-binding antibodies. The study provides a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.

CELL REPORTS (2021)

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Article Microbiology

A cross-neutralizing antibody between HIV-1 and influenza virus

Chang-Chun D. Lee et al.

Summary: This study illustrates the ongoing evolution of oligomannose-type clusters on the surface of human seasonal influenza A H3N2 viruses, as well as the neutralizing effect of 2G12-like antibodies on these clusters. The research further highlights the crucial role of certain glycan sites in the fitness of recent H3N2 strains.

PLOS PATHOGENS (2021)

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Article Chemistry, Multidisciplinary

Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine

Yasunori Watanabe et al.

Summary: Vaccine development targeting the SARS-CoV-2 virus focuses on the S glycoprotein as the principal target of the neutralizing immune response. Adenovirus-vectored vaccines have shown effective processing and assembly of viral antigens, mimicking the observed SARS-CoV-2 virus, making them a promising platform for SARS-CoV-2 vaccines.

ACS CENTRAL SCIENCE (2021)

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Article Chemistry, Multidisciplinary

Assessing Antigen Structural Integrity through Glycosylation Analysis of the SARS-CoV-2 Viral Spike

Juliane Brun et al.

Summary: The study demonstrates the differences in site-specific glycosylation between virus-derived spikes, wild-type non-stabilized spikes, and recombinant engineered spike glycoproteins. Additionally, it shows that their unique cellular secretion pathways lead to distinct protein glycosylation and secretion patterns, including shedding of spike monomeric subunits for the non-stabilized wild-type spike, potentially impacting the resulting immune response and vaccine design.

ACS CENTRAL SCIENCE (2021)

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Article Biochemistry & Molecular Biology

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

Joel D. Allen et al.

Summary: This study investigated the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compared them against S protein from infectious virus, finding conserved patterns across all samples. The results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

BIOCHEMISTRY (2021)

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Review Microbiology

HIV-1 and SARS-CoV-2: Patterns in the evolution of two pandemic pathogens

Will Fischer et al.

Summary: Humanity is currently facing two devastating pandemics caused by two very different RNA viruses: HIV-1 and SARS-CoV-2. The evolution of both viruses is driven by the same evolutionary strategies, such as single nucleotide mutations, multi-base insertions and deletions, recombination, and surface glycan variation. Despite limited diversity in SARS-CoV-2, recent variants still carry Spike mutations that impact antibody resistance and infectivity.

CELL HOST & MICROBE (2021)

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Review Pharmacology & Pharmacy

Current views on N-glycolylneuraminic acid in therapeutic recombinant proteins

Renato Mastrangeli et al.

Summary: The review discusses the structural and functional considerations of Neu5Gc-containing glycans in therapeutic recombinant proteins, including their potential impact on drug clearance, recognition by pre-existing antibodies, and recent hypotheses regarding tolerance to low Neu5Gc levels. Recommendations are provided for standardization of analysis and reporting, relevant analytical aspects for risk assessment associated with Neu5Gc-containing biotherapeutics, and approaches to minimize Neu5Gc incorporation in recombinant protein manufacturing.

TRENDS IN PHARMACOLOGICAL SCIENCES (2021)

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Review Virology

Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development

Eric A. Toth et al.

Summary: An effective vaccine for the hepatitis C virus remains a major unmet medical and public health need, with the E1E2 glycoprotein complex appearing to be the most promising choice. However, challenges in producing this antigen at high levels of purity and integrity remain a bottleneck in vaccine development.

VIRUSES-BASEL (2021)

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Article Multidisciplinary Sciences

Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

Aleksandar Antanasijevic et al.

Summary: The authors proposed a method called cryoEMPEM for high-resolution structural analysis of vaccine-elicited polyclonal antibody responses. By applying this method in rhesus macaques, they were able to determine different polyclonal antibody structures and reveal new epitopes in the immune response.

NATURE COMMUNICATIONS (2021)

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Article Immunology

Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naive human B cells

Jeong Hyun Lee et al.

Summary: The study demonstrates that a successful HIV vaccine must activate naive precursor B cells encoding broadly neutralizing antibodies, and the use of germline-targeting immunogens and high-throughput single-cell BCR sequencing can efficiently screen large numbers of BCR sequences to elucidate precursor frequencies. Furthermore, analysis of IGHV1-2 allelic usage across different cohorts reveals common alleles previously thought incompatible with VRC01-class responses, and germline variation within IGHV1-2 associates with gene usage frequencies in the naive BCR repertoire.

NPJ VACCINES (2021)

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Review Biochemistry & Molecular Biology

Glycans in Virus-Host Interactions: A Structural Perspective

Nathaniel L. Miller et al.

Summary: Glycans play a crucial role in host-microbe interactions, decorating microbial glycoproteins to enhance attachment and fusion to host cells, while also potentially evading the host immune system. Despite being overlooked, they are important in influencing these interactions.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Article Immunology

Glycan Reactive Natural Antibodies and Viral Immunity

J. Stewart New et al.

VIRAL IMMUNOLOGY (2020)

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Review Pharmacology & Pharmacy

Targeting the N332-supersite of the HIV-1 envelope for vaccine design

Thandeka Moyo et al.

EXPERT OPINION ON THERAPEUTIC TARGETS (2020)

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Review Biochemistry & Molecular Biology

Calnexin cycle - structural features of the ER chaperone system

Guennadi Kozlov et al.

FEBS JOURNAL (2020)

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Article Multidisciplinary Sciences

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

Yasunori Watanabe et al.

SCIENCE (2020)

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Article Chemistry, Medicinal

Targeting Endoplasmic Reticulum α-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections

Kelly L. Warfield et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Article Biochemistry & Molecular Biology

Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

Gemma E. Seabright et al.

STRUCTURE (2020)

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Article Multidisciplinary Sciences

Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help

Lina Sun et al.

NATURE COMMUNICATIONS (2020)

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Article Cell Biology

Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines

Bartek Nogal et al.

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Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice

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The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody

Sunita S. Balla-Jhagjhoorsingh et al.

PLOS ONE (2013)

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Article Multidisciplinary Sciences

Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer

Jean-Philippe Julien et al.

SCIENCE (2013)

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Article Multidisciplinary Sciences

Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer

Dmitry Lyumkis et al.

SCIENCE (2013)

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Article Immunology

Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates

Jie Li et al.

VIRAL IMMUNOLOGY (2013)

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Article Microbiology

Correction: The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies

Devin Sok et al.

PLoS Pathogens (2013)

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Article Microbiology

A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies

Rogier W. Sanders et al.

PLOS PATHOGENS (2013)

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Review Immunology

Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies

Peter D. Kwong et al.

IMMUNITY (2012)

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Article Biochemical Research Methods

N-linked Glycan Structures and Their Expressions Change in the Blood Sera of Ovarian Cancer Patients

William R. Alley et al.

JOURNAL OF PROTEOME RESEARCH (2012)

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Article Virology

The Development of CD4 Binding Site Antibodies during HIV-1 Infection

Rebecca M. Lynch et al.

JOURNAL OF VIROLOGY (2012)

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Article Biochemistry & Molecular Biology

STT3B-Dependent Posttranslational N-Glycosylation as a Surveillance System for Secretory Protein

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MOLECULAR CELL (2012)

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Review Cell Biology

Vertebrate protein glycosylation: diversity, synthesis and function

Kelley W. Moremen et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2012)

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A Carboxy-Terminal Trimerization Domain Stabilizes Conformational Epitopes on the Stalk Domain of Soluble Recombinant Hemagglutinin Substrates

Florian Krammer et al.

PLOS ONE (2012)

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Article Multidisciplinary Sciences

HIV-1 incorporation of host-cell-derived glycosphingolipid GM3 allows for capture by mature dendritic cells

Wendy Blay Puryear et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Review Immunology

CD4 binding determinant mimicry for HIV vaccine cesign

Yasuhiro Nishiyama et al.

FRONTIERS IN IMMUNOLOGY (2012)

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Article Virology

Characterization of Glycosylation Profiles of HIV-1 Transmitted/Founder Envelopes by Mass Spectrometry

Eden P. Go et al.

JOURNAL OF VIROLOGY (2011)

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Article Multidisciplinary Sciences

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Jason S. McLellan et al.

NATURE (2011)

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The ESCRT System Is Required for Hepatitis C Virus Production

Yasuo Ariumi et al.

PLOS ONE (2011)

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A Signature in HIV-1 Envelope Leader Peptide Associated with Transition from Acute to Chronic Infection Impacts Envelope Processing and Infectivity

Mohammed Asmal et al.

PLOS ONE (2011)

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Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

Johannes F. Scheid et al.

SCIENCE (2011)

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SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission

Meagan Bolles et al.

CURRENT OPINION IN VIROLOGY (2011)

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Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

S. Gnanakaran et al.

PLOS PATHOGENS (2011)

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Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection

Wei-Chuan Chang et al.

BMC IMMUNOLOGY (2010)

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Direct Complement Restriction of Flavivirus Infection Requires Glycan Recognition by Mannose-Binding Lectin

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CELL HOST & MICROBE (2010)

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Human dendritic cells contain cell surface sialyltransferase activity

M. Guadalupe Cabral et al.

IMMUNOLOGY LETTERS (2010)

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Article Biochemistry & Molecular Biology

Glycosylation Patterns of HIV-1 gp120 Depend on the Type of Expressing Cells and Affect Antibody Recognition

Milan Raska et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

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Article Biotechnology & Applied Microbiology

Identification of a dominant endoplasmic reticulum-retention signal in yellow fever virus pre-membrane protein

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JOURNAL OF GENERAL VIROLOGY (2010)

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Article Biotechnology & Applied Microbiology

Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles

Lynsey Corless et al.

JOURNAL OF GENERAL VIROLOGY (2010)

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Article Biochemistry & Molecular Biology

Expression-System-Dependent Modulation of HIV-1 Envelope Glycoprotein Antigenicity and Immunogenicity

Leopold Kong et al.

JOURNAL OF MOLECULAR BIOLOGY (2010)

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Article Virology

Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16

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JOURNAL OF VIROLOGY (2010)

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Letter Biotechnology & Applied Microbiology

Chinese hamster ovary cells can produce galactose-α-1,3-galactose antigens on proteins

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NATURE BIOTECHNOLOGY (2010)

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Article Multidisciplinary Sciences

Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1

Robert Pejchal et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

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Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

Xueling Wu et al.

SCIENCE (2010)

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Review Cell Biology

Metabolic manipulation of glycosylation disorders in humans and animal models

Hudson H. Freeze et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2010)

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Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

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VIROLOGY (2010)

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Specific interaction of hepatitis C virus glycoproteins with mannan binding lectin inhibits virus entry

Kristelle S. Brown et al.

PROTEIN & CELL (2010)

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Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: Implications for evasion of immune responses and design of vaccine immunogens

Xiaodong Xiao et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2009)

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Review Biochemistry & Molecular Biology

Optimal and consistent protein glycosylation in mammalian cell culture

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GLYCOBIOLOGY (2009)

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N-Linked glycans on dengue viruses grown in mammalian and insect cells

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JOURNAL OF GENERAL VIROLOGY (2009)

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Review Chemistry, Medicinal

Effects of Glycosylation on the Stability of Protein Pharmaceuticals

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JOURNAL OF PHARMACEUTICAL SCIENCES (2009)

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Review Infectious Diseases

Sialic acid tissue distribution and influenza virus tropism

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INFLUENZA AND OTHER RESPIRATORY VIRUSES (2008)

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Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor

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NATURE (2008)

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Effect of glycosylation on protein folding: A close look at thermodynamic stabilization

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles

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VIROLOGY (2008)

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Review Immunology

Mammalian glycosylation in immunity

Jamey D. Marth et al.

NATURE REVIEWS IMMUNOLOGY (2008)

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Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses

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RESPIRATORY RESEARCH (2007)

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Systems Analysis of N-Glycan Processing in Mammalian Cells

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PLOS ONE (2007)

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Review Microbiology

Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy

Jan Balzarini

NATURE REVIEWS MICROBIOLOGY (2007)

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The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein

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Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization

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Control of T cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis

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JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Review Multidisciplinary Sciences

Exploiting the defensive sugars of HIV-1 for drug and vaccine design

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Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor

Catherine M. Radcliffe et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Article Biochemistry & Molecular Biology

Towards abolition of immunogenic structures in insect cells:: characterization of a honey-bee (Apis mellifera) multi-gene family reveals both an allergy-related core α1,3-fucosyltransferase and the first insect Lewis-histo-blood-group-related antigen-synthesizing enzyme

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Review Biochemistry & Molecular Biology

N-linked glycan recognition and processing:: the molecular basis of endoplasmic reticulum quality control

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CURRENT OPINION IN STRUCTURAL BIOLOGY (2006)

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Review Biochemistry & Molecular Biology

N-linked oligosaccharides as outfitters for glycoprotein folding, form and function

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TRENDS IN BIOCHEMICAL SCIENCES (2006)

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Yos9 protein is essential for degradation of misfolded glycoproteins and may function as lectin in ERAD

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MOLECULAR CELL (2005)

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Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins

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The N-X-S/T consensus sequence is required but not sufficient for bacterial N-linked protein glycosylation

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GLYCOBIOLOGY (2005)

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Statistical analysis of the protein environment of N-glycosylation sites:: implications for occupancy, structure, and folding

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GLYCOBIOLOGY (2004)

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Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins:: HIV, SIV, and HCV envelopes and influenza hemagglutinin

M Zhang et al.

GLYCOBIOLOGY (2004)

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Monoglucosylated glycans in the secreted human complement component C3: implications for protein blosynthesis and structure

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Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor

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Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses

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Antibody neutralization and escape by HIV-1

XP Wei et al.

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Review Virology

Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1

RW Sanders et al.

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Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin

XZ Yang et al.

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New insights into the spring-loaded conformational change of influenza virus hemagglutinin

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Intracellular functions of N-linked glycans

A Helenius et al.

SCIENCE (2001)

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Lectins and traffic in the secretory pathway

HP Hauri et al.

FEBS LETTERS (2000)

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Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1

M Saifuddin et al.

JOURNAL OF GENERAL VIROLOGY (2000)

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Review Virology

A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure

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