Search Results

You searched for all publications:

with publication states 'Published (Approved)'
with Tags 'Vaccines'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

45 items found (0 items not approved), displaying 1 to 10.[First/Prev] 1, 2, 3, 4, 5 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I04-Macromolecular Crystallography	Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer’s disease Preeti Bakrania , Gareth Hall , Yvonne Bouter , Caroline Bouter , Nicola Beindorff , Richard Cowan , Sarah Davies , Jemma Price , Chido Mpamhanga , Elizabeth Love , David Matthews , Mark D. Carr , Thomas A. Bayer Molecular Psychiatry 46 DOI: 10.1038/s41380-021-01385-7 Open Access Show Abstract ▼ Abstract: One of the hallmarks of Alzheimer’s disease (AD) are deposits of amyloid-beta (Aβ) protein in amyloid plaques in the brain. The Aβ peptide exists in several forms, including full-length Aβ1-42 and Aβ1-40 – and the N-truncated species, pyroglutamate Aβ3-42 and Aβ4-42, which appear to play a major role in neurodegeneration. We previously identified a murine antibody (TAP01), which binds specifically to soluble, non-plaque N-truncated Aβ species. By solving crystal structures for TAP01 family antibodies bound to pyroglutamate Aβ3-14, we identified a novel pseudo β-hairpin structure in the N-terminal region of Aβ and show that this underpins its unique binding properties. We engineered a stabilised cyclic form of Aβ1-14 (N-Truncated Amyloid Peptide AntibodieS; the ‘TAPAS’ vaccine) and showed that this adopts the same 3-dimensional conformation as the native sequence when bound to TAP01. Active immunisation of two mouse models of AD with the TAPAS vaccine led to a striking reduction in amyloid-plaque formation, a rescue of brain glucose metabolism, a stabilisation in neuron loss, and a rescue of memory deficiencies. Treating both models with the humanised version of the TAP01 antibody had similar positive effects. Here we report the discovery of a unique conformational epitope in the N-terminal region of Aβ, which offers new routes for active and passive immunisation against AD.	Nov 2021
B24-Cryo Soft X-ray Tomography	Correlative imaging using super‐resolution fluorescence microscopy and soft X‐ray tomography at cryogenic temperatures provides a new way to assess virosome solutions for vaccine development Chidinma A. Okolo , Archana Jadhav , Patrick Phillips , Maud Dumoux , Amanda A. Mcmurray , Vishwas D. Joshi , Claire Pizzey , Maria Harkiolaki Journal Of Microscopy DOI: 10.1111/jmi.13054 Diamond Proposal Number(s): [24622] Open Access Show Abstract ▼ Abstract: Active Virosomes (AVs) are derivatives of viruses, broadly similar to ‘parent’ pathogens, with an outer envelope that contains a bespoke genome coding for 4–5 viral proteins capable of eliciting an antigenic response. AVs are essentially novel vaccine formulations that present on their surface selected viral proteins as antigens. Once administered, they elicit an initial “anti-viral” immune response. AVs are also internalised by host cells where their cargo viral genes are used to express viral antigen(s) intracellularly. These can then be transported to the host cell surface resulting in a second wave of antigen exposure and a more potent immuno-stimulation. A new 3D correlative microscopy approach is used here to provide a robust analytical method for characterisation of Zika and Chikungunya-derivatised AV populations including vesicle size distribution and variations in antigen loading. Manufactured batches were compared to assess the extent and nature of batch-to-batch variations. We also show preliminary results that verify antigen expression on the surface of host cells. We present here a reliable and efficient high-resolution 3D imaging regime that allows the evaluation of the microstructure and biochemistry of novel vaccine formulations such as AVs.	Aug 2021
I22-Small angle scattering & Diffraction	A potential new method for vaccines without refrigeration Asel Sartbaeva Diamond Proposal Number(s): [14148] Show Abstract ▼ Abstract: Almost all vaccines require refrigeration or freezing conditions for storage and transport. A vaccine cold chain has been developed to DA An international team of researchers, led by Dr Asel Sartbaeva, has developed a novel method of making existing vaccines thermally stable so that they will not depend on cold chain distribution. The process uses silica (SiO2) to create layers of inorganic materials around individual vaccine components. This ensilication results in nanoparticles of silica with protein in the middle. The team performed in situ Small Angle X-ray Scattering (SAXS) measurements during ensilication, on Diamond Light Source’s Time-Resolved SAXS & Diffraction beamline (I22). They chose to study tetanus toxin C fragment (TTCF), an inactive component of the tetanus toxin present in the diphtheria, tetanus and pertussis (DTP) vaccine. Their results demonstrated that ensilication maintained the vaccine effect. All biopharmaceuticals have unique functions that require different environments for their operation. For some, lyophilisation (freeze-drying) may be the optimum choice for stabilising and transporting the bioactive compounds. However, this new methodology provides another solution for biopharmaceutical stabilisation and could help to increase vaccine transport and administration all around the world.	Jul 2021
I03-Macromolecular Crystallography Krios I-Titan Krios I at Diamond	Structural basis for a neutralizing antibody response elicited by a recombinant hantaan virus Gn immunogen Ilona Rissanen , Stefanie A. Krumm , Robert Stass , Annalis Whitaker , James E. Voss , Emily A. Bruce , Sylvia Rothenberger , Stefan Kunz , Dennis R. Burton , Juha T. Huiskonen , Jason W. Botten , Thomas A. Bowden , Katie J. Doores Mbio 146 DOI: 10.1128/mBio.02531-20 Diamond Proposal Number(s): [19946, 20223] Open Access Show Abstract ▼ Abstract: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)4 spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design.	Jul 2021
	Site-specific steric control of SARS-COV-2 spike glycosylation Joel D. Allen , Himanshi Chawla , Firdaus Samsudin , Lorena Zuzic , Aishwary Tukaram Shivgan , Yasunori Watanabe , Wan-Ting He , Sean Callaghan , Ge Song , Peter Yong , Philip J. M. Brouwer , Yutong Song , Yongfei Cai , Helen M. E. Duyvesteyn , Tomas Malinauskas , Joeri Kint , Paco Pino , Maria J. Wurm , Martin Frank , Bing Chen , David I. Stuart , Rogier W. Sanders , Raiees Andrabi , Dennis R. Burton , Sai Li , Peter J. Bond , Max Crispin Biochemistry DOI: 10.1021/acs.biochem.1c00279 Open Access Show Abstract ▼ Abstract: A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.	Jul 2021
I03-Macromolecular Crystallography	Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum Chang Liu , Helen M. Ginn , Wanwisa Dejnirattisai , Piyada Supasa , Beibei Wang , Aekkachai Tuekprakhon , Rungtiwa Nutalai , Daming Zhou , Alexander J. Mentzer , Yuguang Zhao , Helen M. E. Duyvesteyn , César López-Camacho , Jose Slon-Campos , Thomas Walter , Donal Skelly , Sile Ann Johnson , Thomas G. Ritter , Chris Mason , Sue Ann Costa Clemens , Felipe Gomes Naveca , Valdinete Nascimento , Fernanda Nascimento , Cristiano Fernandes Da Costa , Paola Cristina Resende , Alex Pauvolid-Correa , Marilda M. Siqueira , Christina Dold , Nigel Temperton , Tao Dong , Andrew J. Pollard , Julian C. Knight , Derrick Crook , Teresa Lambe , Elizabeth Clutterbuck , Sagida Bibi , Amy Flaxman , Mustapha Bittaye , Sandra Belij-Rammerstorfer , Sarah C. Gilbert , Tariq Malik , Miles W. Carroll , Paul Klenerman , Eleanor Barnes , Susanna J. Dunachie , Vicky Baillie , Natali Serafin , Zanele Ditse , Kelly Da Silva , Neil G. Paterson , Mark A. Williams , David R. Hall , Shabir Madhi , Marta C. Nunes , Philip Goulder , Elizabeth E. Fry , Juthathip Mongkolsapaya , Jingshan Ren , David I. Stuart , Gavin R. Screaton Cell DOI: 10.1016/j.cell.2021.06.020 Diamond Proposal Number(s): [27009] Show Abstract ▼ Abstract: SARS-CoV-2 has undergone progressive change with variants conferring advantage rapidly becoming dominant lineages e.g. B.1.617. With apparent increased transmissibility variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the UK. Here we study the ability of monoclonal antibodies, convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2 and complement this with structural analyses of Fab/RBD complexes and map the antigenic space of current variants. Neutralization of both viruses is reduced when compared with ancestral Wuhan related strains but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2 suggesting that individuals previously infected by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insight for immunisation policy with future variant vaccines in non-immune populations.	Jun 2021
	Making the invisible enemy visible Tristan I. Croll , Kay Diederichs , Florens Fischer , Cameron D. Fyfe , Yunyun Gao , Sam Horrell , Agnel Praveen Joseph , Luise Kandler , Oliver Kippes , Ferdinand Kirsten , Konstantin Müller , Kristopher Nolte , Alexander M. Payne , Matthew Reeves , Jane S. Richardson , Gianluca Santoni , Sabrina Stäb , Dale E. Tronrud , Lea C. Von Soosten , Christopher J. Williams , Andrea Thorn Nature Structural & Molecular Biology 28, 404 - 408 DOI: 10.1038/s41594-021-00593-7 Show Abstract ▼ Abstract: Structural biology plays a crucial role in the fight against COVID-19, permitting us to ‘see’ and understand SARS-CoV-2. However, the macromolecular structures of SARS-CoV-2 proteins that were solved with great speed and urgency can contain errors that may hinder drug design. The Coronavirus Structural Task Force has been working behind the scenes to evaluate and improve these structures, making the results freely available at https://insidecorona.net/.	May 2021
Krios II-Titan Krios II at Diamond	Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine Yasunori Watanabe , Luiza Mendonca , Elizabeth R. Allen , Andrew Howe , Mercede Lee , Joel D. Allen , Himanshi Chawla , David Pulido , Francesca Donnellan , Hannah Davies , Marta Ulaszewska , Sandra Belij-Rammerstorfer , Susan Morris , Anna-Sophia Krebs , Wanwisa Dejnirattisai , Juthathip Mongkolsapaya , Piyada Supasa , Gavin R. Screaton , Catherine M. Green , Teresa Lambe , Peijun Zhang , Sarah C. Gilbert , Max Crispin Acs Central Science DOI: 10.1021/acscentsci.1c00080 Diamond Proposal Number(s): [18477, 21005, 21004] Show Abstract ▼ Abstract: Vaccine development against the SARS-CoV-2 virus focuses on the principal target of the neutralizing immune response, the spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for the delivery of viral antigen, but it is important for the generation of neutralizing antibodies that they produce appropriately processed and assembled viral antigen that mimics that observed on the SARS-CoV-2 virus. Here, we describe the structure, conformation, and glycosylation of the S protein derived from the adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate native-like post-translational processing and assembly, and reveal the expression of S proteins on the surface of cells adopting the trimeric prefusion conformation. The data presented here confirm the use of ChAdOx1 adenovirus vectors as a leading platform technology for SARS-CoV-2 vaccines.	Apr 2021
I03-Macromolecular Crystallography	Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai , Daming Zhou , Piyada Supasa , Chang Liu , Alexander J. Mentzer , Helen M. Ginn , Yuguang Zhao , Helen M. E. Duyvesteyn , Aekkachai Tuekprakhon , Rungtiwa Nutalai , Beibei Wang , Guido Paesen , César López-Camacho , Jose Slon-Campos , Thomas S. Walter , Donal Skelly , Sue Ann Costa Clemens , Felipe Gomes Naveca , Valdinete Nascimento , Fernanda Nascimento , Cristiano Fernandes Da Costa , Paola C. Resende , Alex Pauvolid-Correa , Marilda M. Siqueira , Christina Dold , Robert Levin , Tao Dong , Andrew J. Pollard , Julian C. Knight , Derrick Crook , Teresa Lambe , Elizabeth Clutterbuck , Sagida Bibi , Amy Flaxman , Mustapha Bittaye , Sandra Belij-Rammerstorfer , Sarah Gilbert , Miles W. Carroll , Paul Klenerman , Eleanor Barnes , Susanna J. Dunachie , Neil G. Paterson , Mark A. Williams , David R. Hall , Ruben J. G. Hulswit , Thomas A. Bowden , Elizabeth E. Fry , Juthathip Mongkolsapaya , Jingshan Ren , David I. Stuart , Gavin R. Screaton Cell DOI: 10.1016/j.cell.2021.03.055 Diamond Proposal Number(s): [27009] Open Access Show Abstract ▼ Abstract: Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.	Mar 2021
I03-Macromolecular Crystallography	Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera Piyada Supasa , Daming Zhou , Wanwisa Dejnirattisai , Chang Liu , Alexander J. Mentzer , Helen M. Ginn , Yuguang Zhao , Helen M. E. Duyvesteyn , Rungtiwa Nutalai , Aekkachai Tuekprakhon , Beibei Wang , Guido Paesen , Jose Slon-Campos , César López-Camacho , Bassam Hallis , Naomi Coombes , Kevin Bewley , Sue Charlton , Thomas S. Walter , Eleanor Barnes , Susanna J. Dunachie , Donal Skelly , Sheila F. Lumley , Natalie Baker , Imam Shaik , Holly Humphries , Kerry Godwin , Nick Gent , Alex Sienkiewicz , Christina Dold , Robert Levin , Tao Dong , Andrew J. Pollard , Julian C. Knight , Paul Klenerman , Derrick Crook , Teresa Lambe , Elizabeth Clutterbuck , Sagida Bibi , Amy Flaxman , Mustapha Bittaye , Sandra Belij-Rammerstorfer , Sarah Gilbert , David R. Hall , Mark Williams , Neil G. Paterson , William James , Miles W. Carroll , Elizabeth E. Fry , Juthathip Mongkolsapaya , Jingshan Ren , David I. Stuart , Gavin R. Screaton Cell DOI: 10.1016/j.cell.2021.02.033 Diamond Proposal Number(s): [27009] Open Access Show Abstract ▼ Abstract: SARS-CoV-2 has caused over 2M deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbours 9 amino-acid changes in the spike, including N501Y in the ACE2 interacting-surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterised monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.	Feb 2021

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User