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| Open AccessMultivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans
Immunologically-active glycans are promising vaccine candidates but can be difficult to synthesize. Here, the authors show that pentavalent display of a minimal disaccharde epitope on a chemical scaffold can mimic a native C. difficileglycan antigen, representing a simple approach to synthetic vaccine production.
- Felix Broecker
- , Jonas Hanske
- & Peter H. Seeberger
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| Open AccessT-cell activation is an immune correlate of risk in BCG vaccinated infants
BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR+CD4+T cells.
- Helen A. Fletcher
- , Margaret A. Snowden
- & Helen McShane
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| Open AccessType 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice
Type 1 diabetes is associated with the loss of self-tolerance to the insulin-producing β-cells in the pancreas. Here the authors show that vaccination with insulin mimetopes can induce human insulin-specific regulatory T cells to mediate tolerance in a humanized mouse model.
- Isabelle Serr
- , Rainer W. Fürst
- & Carolin Daniel
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| Open AccessFollicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
T follicular regulatory cells control the magnitude of the germinal centre response. Here the authors show that these cells display specificity to self as well as foreign antigens, and can arise from Foxp3-negative precursors at early stages of immunization in a PD-L1 dependent manner.
- Meryem Aloulou
- , Edward J. Carr
- & Michelle A. Linterman
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| Open AccessPre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination
Ageing is associated with poor responses to vaccines but the underlying mechanism remains unclear. Here the authors use a systems-based approach to define molecular signatures present before vaccination that correlate with non-responsiveness to hepatitis B vaccination in healthy, elderly adults.
- Slim Fourati
- , Razvan Cristescu
- & Rafick-Pierre Sékaly
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| Open AccessA highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
Respiratory syncytial virus (RSV) is a highly contagious childhood pathogen of the respiratory tract for which no vaccine is currently available. Here the authors present a strategy to stabilize the RSV F protein in a prefusion conformation that can elicit a strong protective immune response in animal models.
- Anders Krarup
- , Daphné Truan
- & Johannes P. M. Langedijk
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| Open AccessDevelopment of high-yield influenza A virus vaccine viruses
The availability of high-yield virus strains remains an important bottleneck in the rapid production of influenza vaccines. Here, the authors report the development of influenza A vaccine backbone that improves the virus yield of various seasonal and pandemic influenza vaccine strains in cell culture.
- Jihui Ping
- , Tiago J.S. Lopes
- & Yoshihiro Kawaoka
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| Open AccessEvaluation of candidate vaccine approaches for MERS-CoV
Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development.
- Lingshu Wang
- , Wei Shi
- & Barney S. Graham
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| Open AccessA potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.
- Ying Wu
- , MyungSam Cho
- & Ruben O. Donis
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| Open AccessAnalysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization
HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.
- Joseph R. Francica
- , Zizhang Sheng
- & Robert A. Seder
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Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo
Activation of TLRs by microbial ligands induces complex innate immune responses to activate host defence. Here the authors show that a synthetic TLR3 ligand can boost protective immunity without robust inflammatory cytokine production, minimizing toxic effects of immunization.
- Misako Matsumoto
- , Megumi Tatematsu
- & Tsukasa Seya
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| Open AccessExploiting light chains for the scalable generation and platform purification of native human bispecific IgG
Bispecific antibodies allow for novel therapeutic approaches but industrial-scale production and immunogenicity represent significant challenges. Here Fischer et al.describe a unique human bispecific antibody format that exploits differing light chains to overcome these obstacles.
- Nicolas Fischer
- , Greg Elson
- & Marie Kosco-Vilbois
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| Open AccessStructural basis of IL-23 antagonism by an Alphabody protein scaffold
Protein scaffolds can serve as alternatives to antibodies in a range of applications. Here, the authors report the design and development of Alphabody™, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold that the authors use to develop Alphabodies that can neutralize human IL-23 with high specificity and affinity.
- Johan Desmet
- , Kenneth Verstraete
- & Savvas N. Savvides
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| Open AccessClearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients
While several human papilloma virus (HPV) vaccines exist, a highly effective vaccine that mediates regression of HPV-induced tumours is lacking. Here the authors show that a therapeutic DNA vaccine-induced HPV-specific polyfunctional CD8 T cell in 7 out of 9 patients who all exhibited complete regression of lesions and viral clearance.
- Tae Jin Kim
- , Hyun-Tak Jin
- & Young Chul Sung
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Scalable high-density peptide arrays for comprehensive health monitoring
Health monitoring based on measuring circulating antibodies may enable the presymptomatic detection of diseases. Here, the authors report a large-scale peptide array platform that allows for a detection of the profile of circulating antibodies associated with cancers and infectious diseases.
- Joseph Barten Legutki
- , Zhan-Gong Zhao
- & Phillip Stafford
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IgGs are made for walking on bacterial and viral surfaces
Antibody–antigen recognition is one of the important aspects of immunity, but the nanomechanical process of this recognition is not fully understood. Here, using high-speed atomic force microscopy, the authors observe that on membranes containing a high density of immobile antigens antibodies move in a ‘random walking’ motion.
- Johannes Preiner
- , Noriyuki Kodera
- & Peter Hinterdorfer
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Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection
Viral antigens can persist within the secondary lymphoid tissues of the host for many weeks after resolution of the infection. Tamburini et al.demonstrate that antigens remaining following viral infection or vaccination can be captured and maintained for extended periods of time by lymphatic endothelial cells.
- Beth A. Tamburini
- , Matthew A. Burchill
- & Ross M. Kedl
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Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus
Influenza A H3 viruses circulate in humans and bind host cells using the haemagglutinin (HA) glycoprotein. Here, Lee et al.perform a structural analysis of antibody F045–092 with broadly neutralizing activity against the H3 subtype and reveal its interaction with the HA receptor binding site.
- Peter S. Lee
- , Nobuko Ohshima
- & Ian A. Wilson
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Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery
Bacterial type III secretion systems (T3SS) improve the delivery of vaccine antigens and antigen-specific immune responses but require the use of live vaccines. Carleton et al. report the assembly of a functional T3SS in replication-incompetent bacterial minicells that can deliver vaccine antigens in vitro and in vivo.
- Heather A. Carleton
- , María Lara-Tejero
- & Jorge E. Galán
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Mapping of H3N2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation
Influenza vaccines are updated frequently to accommodate changing influenza antigenicity. Here, the authors develop a new computational method for predicting the antigenicity of H3N2 influenza strains based on the HA sequence.
- Xiangjun Du
- , Libo Dong
- & Taijiao Jiang