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1. Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

Author

Liu, Chang, Das, Raksha, Dijokaite-Guraliuc, Aiste, Zhou, Daming, Mentzer, Alexander J., Supasa, Piyada, Selvaraj, Muneeswaran, Duyvesteyn, Helen M. E., Ritter, Thomas G., Temperton, Nigel, Klenerman, Paul, Dunachie, Susanna J., Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2024
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3. Sample Preparation and Data Collection for High-Speed Fixed-Target Serial Femtosecond Crystallography

Author

Meents, Alke, Roedig, Philip, Ginn, Helen M, Pakendorf, Tim, Sutton, Geoff, Harlos, Karl, Walter, Thomas S, Meyer, Jan, Fischer, Pontus, Duman, Ramona, Vartiainen, Ismo, Reime, Bernd, Warmer, Martin, Brewster, Aaron S, Young, Iris D, Clark, Tara Michels, Sauter, Nicholas K, Sikorsky, Marcin, Nelson, Silke, Damiani, Daniel S, Alonso-Mori, Roberto, Ren, Jingshan, Fry, Elizabeth E, David, Christian, Stuart, David I, and Wagner, Armin H

Published
2023

4. A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Author

Liu, Chang, Zhou, Daming, Dijokaite-Guraliuc, Aiste, Supasa, Piyada, Duyvesteyn, Helen M.E., Ginn, Helen M., Selvaraj, Muneeswaran, Mentzer, Alexander J., Das, Raksha, de Silva, Thushan I., Ritter, Thomas G., Plowright, Megan, Newman, Thomas A.H., Stafford, Lizzie, Kronsteiner, Barbara, Temperton, Nigel, Lui, Yuan, Fellermeyer, Martin, Goulder, Philip, Klenerman, Paul, Dunachie, Susanna J., Barton, Michael I., Kutuzov, Mikhail A., Dushek, Omer, Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2024
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5. Computes: Development of an Instrument to Measure Introductory Statistics Instructors' Emphasis on Computational Practices

Author

Legacy, Chelsey, Zieffler, Andrew, Fry, Elizabeth Brondos, and Le, Laura

Abstract

The influx of data and the advances in computing have led to calls to update the introductory statistics curriculum to better meet the needs of the contemporary workforce. To this end, we developed the COMputational Practices in Undergraduate TEaching of Statistics (COMPUTES) instrument, which can be used to measure the extent to which computation practices--specifically data, simulation, and coding practices--are included in the introductory statistics curriculum. Data from 236 instructors were used in a psychometric analysis to evaluate the latent structure underlying instructors' response patterns and understand the quality of the items. We also examined whether computational practices are being emphasized differently across institutional settings. Results suggest that the latent structure is best captured using a correlated multidimensional model and that most items were contributing information to the measurement process. Across institutional settings, curricular emphasis related to data and simulation practices seem quite similar, while emphasis on coding practices differs.

Published
2022
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6. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

Author

Conlon, Christopher, Deeks, Alexandra, Frater, John, Gardiner, Siobhan, Jämsén, Anni, Jeffery, Katie, Malone, Tom, Phillips, Eloise, Kronsteiner-Dobramysl, Barbara, Abraham, Priyanka, Bibi, Sagida, Lambe, Teresa, Longet, Stephanie, Tipton, Tom, Carrol, Miles, Stafford, Lizzie, Dijokaite-Guraliuc, Aiste, Das, Raksha, Zhou, Daming, Ginn, Helen M., Liu, Chang, Duyvesteyn, Helen M.E., Huo, Jiandong, Nutalai, Rungtiwa, Supasa, Piyada, Selvaraj, Muneeswaran, de Silva, Thushan I., Plowright, Megan, Newman, Thomas A.H., Hornsby, Hailey, Mentzer, Alexander J., Skelly, Donal, Ritter, Thomas G., Temperton, Nigel, Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Roemer, Cornelius, Peacock, Thomas P., Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2023
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7. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75

Author

Huo, Jiandong, Dijokaite-Guraliuc, Aiste, Liu, Chang, Zhou, Daming, Ginn, Helen M., Das, Raksha, Supasa, Piyada, Selvaraj, Muneeswaran, Nutalai, Rungtiwa, Tuekprakhon, Aekkachai, Duyvesteyn, Helen M.E., Mentzer, Alexander J., Skelly, Donal, Ritter, Thomas G., Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Paterson, Neil G., Williams, Mark A., Hall, David R., Plowright, Megan, Newman, Thomas A.H., Hornsby, Hailey, de Silva, Thushan I., Temperton, Nigel, Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Pollard, Andrew J., Lambe, Teresa, Goulder, Philip, Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2023
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12. The Teaching of Introductory Statistics: Results of a National Survey.

Author

Legacy, Chelsey, Le, Laura, Zieffler, Andrew, Fry, Elizabeth, and Vivas Corrales, Pablo

Subjects
EDUCATION statistics, STATISTICS
Abstract

The Statistics Teaching Inventory (STI) was designed to assess the teaching practices of U.S.-based, college-level introductory statistics instructors in a variety of institutions and departments. This instrument has now been updated to reflect current trends and recommendations in statistics education. In this study, we used the STI to examine the current state of the curricular and instructional practices being used by U.S.-based, college-level introductory statistics instructors. We explore the extent to which instructors report that their introductory statistics courses are aligned with recommended practices as outlined by the 2016 GAISE College Report. Data were collected from a sample of college-level U.S.-based, college-level introductory statistics instructors. Results based on 228 usable responses indicated that instructors, by-and-large, tended to be following the GAISE recommendations, especially related to content. However, courses may not yet be aligned with newer content recommendations (e.g., provide students opportunities to work with multivariate data), and there is still a large percentage of instructors that are not embracing student-oriented pedagogies and assessment methods. for this article are available online. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Paint-By-Number or Picasso? A Grounded Theory Phenomenographical Study of Students' Conceptions of Statistics

Author

Justice, Nicola, Morris, Samantha, Henry, Veronique, and Fry, Elizabeth Brondos

Abstract

Statistics students' conceptions of the work of statisticians and the discipline of statistics may play an important role in the topics to which they attend and their interest in pursuing further study. To learn about students' conceptions, we collected open-ended survey responses from 44 undergraduate students who had completed introductory statistics courses. We used a grounded theory phenomenographical qualitative approach to identify several themes in students' conceptions. In addition to the test-and-procedure conception, we offer several other themes, such as acknowledgement of variation and the role of ethical integrity. We use a metaphor of painting styles to compare to experts' conceptions of statistics. By identifying "seeds" of what may be developed into expert conceptions, these preliminary results set possible foundations to explore trajectories that may help shape students' conceptions of statistics.

Published
2020

14. The CATALST Curriculum: A Story of Change

Author

Justice, Nicola, Le, Laura, Sabbag, Anelise, Fry, Elizabeth, Ziegler, Laura, and Garfield, Joan

Abstract

One of the first simulation-based introductory statistics curricula to be developed was the NSF-funded Change Agents for Teaching and Learning Statistics curriculum. True to its name, this curriculum is constantly undergoing change. This article describes the story of the curriculum as it has evolved at the University of Minnesota and offers insight into promising new future avenues for the curriculum to continue to affect radical, substantive change in the teaching and learning of statistics. Supplementary materials for this article are available online.

Published
2020
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15. High-speed fixed-target serial virus crystallography

Author

Roedig, Philip, Ginn, Helen M, Pakendorf, Tim, Sutton, Geoff, Harlos, Karl, Walter, Thomas S, Meyer, Jan, Fischer, Pontus, Duman, Ramona, Vartiainen, Ismo, Reime, Bernd, Warmer, Martin, Brewster, Aaron S, Young, Iris D, Michels-Clark, Tara, Sauter, Nicholas K, Kotecha, Abhay, Kelly, James, Rowlands, David J, Sikorsky, Marcin, Nelson, Silke, Damiani, Daniel S, Alonso-Mori, Roberto, Ren, Jingshan, Fry, Elizabeth E, David, Christian, Stuart, David I, Wagner, Armin, and Meents, Alke

Subjects
Biological Sciences, Infection, Algorithms, Crystallography, X-Ray, Image Enhancement, Image Interpretation, Computer-Assisted, Imaging, Three-Dimensional, Reproducibility of Results, Sample Size, Sensitivity and Specificity, Viruses, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities.

Published
2017

16. The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.

Author

Clarke, John D., Douangamath, Alice, Mikolajek, Halina, Bonnet-Di Placido, Marie, Ren, Jingshan, Fry, Elizabeth E., Stuart, Dave I., Hammond, John A., and Owens, Raymond J.

Subjects
IMMUNOGLOBULINS, BOS, MONOCLONAL antibodies, X-ray crystallography
Abstract

The third complementary‐determining regions of the heavy‐chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These 'ultralong' CDR3Hs form β‐ribbon stalks that protrude from the surface of the antibody with a disulfide cross‐linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B‐cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen‐unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Author

Zhou, Daming, Duyvesteyn, Helen M. E., Chen, Cheng-Pin, Huang, Chung-Guei, Chen, Ting-Hua, Shih, Shin-Ru, Lin, Yi-Chun, Cheng, Chien-Yu, Cheng, Shu-Hsing, Huang, Yhu-Chering, Lin, Tzou-Yien, Ma, Che, Huo, Jiandong, Carrique, Loic, Malinauskas, Tomas, Ruza, Reinis R., Shah, Pranav N. M., Tan, Tiong Kit, Rijal, Pramila, Donat, Robert F., Godwin, Kerry, Buttigieg, Karen R., Tree, Julia A., Radecke, Julika, Paterson, Neil G., Supasa, Piyada, Mongkolsapaya, Juthathip, Screaton, Gavin R., Carroll, Miles W., Gilbert-Jaramillo, Javier, Knight, Michael L., James, William, Owens, Raymond J., Naismith, James H., Townsend, Alain R., Fry, Elizabeth E., Zhao, Yuguang, Ren, Jingshan, Stuart, David I., and Huang, Kuan-Ying A.

Published
2020
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24. Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Author

Ragonnet-Cronin, Manon, primary, Nutalai, Rungtiwa, additional, Huo, Jiandong, additional, Dijokaite-Guraliuc, Aiste, additional, Das, Raksha, additional, Tuekprakhon, Aekkachai, additional, Supasa, Piyada, additional, Liu, Chang, additional, Selvaraj, Muneeswaran, additional, Groves, Natalie, additional, Hartman, Hassan, additional, Ellaby, Nicholas, additional, Mark Sutton, J., additional, Bahar, Mohammad W., additional, Zhou, Daming, additional, Fry, Elizabeth, additional, Ren, Jingshan, additional, Brown, Colin, additional, Klenerman, Paul, additional, Dunachie, Susanna J., additional, Mongkolsapaya, Juthathip, additional, Hopkins, Susan, additional, Chand, Meera, additional, Stuart, David I., additional, Screaton, Gavin R., additional, and Rokadiya, Sakib, additional

Published
2023
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27. A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation

Author

Bahar, Mohammad W, Nasta, Veronica, Fox, Helen, Sherry, Lee, Grehan, Keith, Porta, Claudine, Macadam, Andrew J, Stonehouse, Nicola J, Rowlands, David J, Fry, Elizabeth E, Stuart, David I, Bahar, Mohammad W [0000-0002-2350-2682], Sherry, Lee [0000-0002-4367-772X], Grehan, Keith [0000-0003-3976-756X], Macadam, Andrew J [0000-0002-8687-1573], Stonehouse, Nicola J [0000-0003-1146-5519], Rowlands, David J [0000-0002-4742-9272], Fry, Elizabeth E [0000-0001-9754-5303], Stuart, David I [0000-0002-3426-4210], and Apollo - University of Cambridge Repository

Subjects
Poliovirus, Sulfonamides, Binding Sites, Medicine (miscellaneous), Benzene, Vaccines, Virus-Like Particle, General Agricultural and Biological Sciences, Antiviral Agents, Antigens, Viral, Glutathione, General Biochemistry, Genetics and Molecular Biology, Enterovirus
Abstract

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

Published
2022

28. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

Author

Dijokaite-Guraliuc, Aiste, primary, Das, Raksha, additional, Zhou, Daming, additional, Ginn, Helen M., additional, Liu, Chang, additional, Duyvesteyn, Helen M.E., additional, Huo, Jiandong, additional, Nutalai, Rungtiwa, additional, Supasa, Piyada, additional, Selvaraj, Muneeswaran, additional, de Silva, Thushan I., additional, Plowright, Megan, additional, Newman, Thomas A.H., additional, Hornsby, Hailey, additional, Mentzer, Alexander J., additional, Skelly, Donal, additional, Ritter, Thomas G., additional, Temperton, Nigel, additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Roemer, Cornelius, additional, Peacock, Thomas P., additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Fry, Elizabeth E., additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Stuart, David I., additional, Screaton, Gavin R., additional, Conlon, Christopher, additional, Deeks, Alexandra, additional, Frater, John, additional, Gardiner, Siobhan, additional, Jämsén, Anni, additional, Jeffery, Katie, additional, Malone, Tom, additional, Phillips, Eloise, additional, Kronsteiner-Dobramysl, Barbara, additional, Abraham, Priyanka, additional, Bibi, Sagida, additional, Lambe, Teresa, additional, Longet, Stephanie, additional, Tipton, Tom, additional, Carrol, Miles, additional, and Stafford, Lizzie, additional

Published
2023
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29. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2 directed antibody responses

Author

Dijokaite-Guraliuc, Aiste, Das, Raksha, Zhou, Daming, Ginn, Helen M., Liu, Chang, Duyvesteyn, Helen M.E., Huo, Jiandong, Nutalai, Rungtiwa, Supasa, Piyada, Selvaraj, Muneeswaran, de Silva, Thushan I., Plowright, Megan, Newman, Thomas A.H., Hornsby, Hailey, Mentzer, Alexander J., Skelly, Donal, Ritter, Thomas G., Temperton, Nigel, Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Roemer, Cornelius, Peacock, Thomas P., Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., Screaton, Gavin R., Dijokaite-Guraliuc, Aiste, Das, Raksha, Zhou, Daming, Ginn, Helen M., Liu, Chang, Duyvesteyn, Helen M.E., Huo, Jiandong, Nutalai, Rungtiwa, Supasa, Piyada, Selvaraj, Muneeswaran, de Silva, Thushan I., Plowright, Megan, Newman, Thomas A.H., Hornsby, Hailey, Mentzer, Alexander J., Skelly, Donal, Ritter, Thomas G., Temperton, Nigel, Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Roemer, Cornelius, Peacock, Thomas P., Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Abstract

In November 2021 Omicron BA.1, containing a raft of new spike mutations emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or SARS-CoV-2 infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional RBD amino-acid substitutions compared to BA.2. We describe a panel of 25 potent mAbs generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titre of vaccine or BA.1, BA.2 or BA.4/5 immune serum.

Published
2023

30. Isolation of a pair of potent broadly neutralizing mAb binding to RBD and SD1 domains of SARS-CoV-2

Author

Stuart, David, Liu, Chang, Das, Raksha, Dijokaite-Guraliuc, Aiste, Zhou, Daming, Duyvesteyn, Helen, Mentzer, Alexander, Supasa, Piyasa, Selvaraj, Muneeswaran, Ritter, Thomas, Temperton, Nigel, Klenerman, Paul, Dunachie, Susanna, Paterson, Neil, Williams, Mark, Hall, David, Fry, Elizabeth, Mongkolsapaya, Juthathip, Ren, Jingshan, Screaton, Gavin, Stuart, David, Liu, Chang, Das, Raksha, Dijokaite-Guraliuc, Aiste, Zhou, Daming, Duyvesteyn, Helen, Mentzer, Alexander, Supasa, Piyasa, Selvaraj, Muneeswaran, Ritter, Thomas, Temperton, Nigel, Klenerman, Paul, Dunachie, Susanna, Paterson, Neil, Williams, Mark, Hall, David, Fry, Elizabeth, Mongkolsapaya, Juthathip, Ren, Jingshan, and Screaton, Gavin

Abstract

Commercially developed monoclonal antibodies (mAb) have been effective in the prevention or treatment of SARS-CoV-2 infection1-3 but the rapid antigenic evolution of the Omicron sub-lineages has reduced their activity4-8 and they are no longer licensed for use in many countries. Here, we isolate spike binding monoclonal antibodies from vaccinees who suffered vaccine break-through infections with Omicron sublineages BA.4/5. We find that it is possible for antibodies targeting highly mutated regions to recover broad activity through allosteric effects (mAb BA.4/5-35) and characterise a pair of potent mAbs with extremely broad neutralization against current and historical SARS-CoV-2 variants. One, mAb BA.4/5-2, binds at the back of the left shoulder of the receptor binding domain (RBD) in an area which has resisted mutational change to date. The second, mAb BA.4/5-5, binds a conserved epitope in sub-domain 1 (SD1). The isolation of this pair of antibodies with non-overlapping epitopes shows that potent and extremely broadly neutralizing antibodies are still generated following infection and SD1 directed mAbs may increase the resilience of mAb therapeutics/prophylactics against SARS-CoV-2.

Published
2023

34. Production and Characterisation of Stabilised PV-3 Virus-like Particles Using Pichia pastoris

Author

Sherry, Lee, Grehan, Keith, Swanson, Jessica J, Bahar, Mohammad W, Porta, Claudine, Fry, Elizabeth E, Stuart, David I, Rowlands, David J, Stonehouse, Nicola J, Sherry, Lee [0000-0002-4367-772X], Grehan, Keith [0000-0003-3976-756X], Bahar, Mohammad W [0000-0002-2350-2682], Stuart, David I [0000-0002-3426-4210], Rowlands, David J [0000-0002-4742-9272], Stonehouse, Nicola J [0000-0003-1146-5519], and Apollo - University of Cambridge Repository

Subjects
Poliovirus Vaccines, poliovirus, vaccine, virus-like particle, Pichia pastoris, Poliovirus, Infectious Diseases, Poliovirus Vaccine, Oral, Virology, Humans, Antibodies, Viral, Poliomyelitis
Abstract

Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally-stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly-expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.

Published
2022
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36. Nonlytic cellular release of hepatitis A virus requires dual capsid recruitment of the ESCRT-associated Bro1 domain proteins HD-PTP and ALIX

Author

Shirasaki, Takayoshi, primary, Feng, Hui, additional, Duyvesteyn, Helen M. E., additional, Fusco, William G., additional, McKnight, Kevin L., additional, Xie, Ling, additional, Boyce, Mark, additional, Kumar, Sathish, additional, Barouch-Bentov, Rina, additional, González-López, Olga, additional, McNamara, Ryan, additional, Wang, Li, additional, Hertel-Wulff, Adriana, additional, Chen, Xian, additional, Einav, Shirit, additional, Duncan, Joseph A., additional, Kapustina, Maryna, additional, Fry, Elizabeth E., additional, Stuart, David I., additional, and Lemon, Stanley M., additional

Published
2022
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38. Toremifene interacts with and destabilizes the Ebola virus glycoprotein

Author

Zhao, Yuguang, Ren, Jingshan, Harlos, Karl, Jones, Daniel M., Zeltina, Antra, Bowden, Thomas A., Padilla-Parra, Sergi, Fry, Elizabeth E., and Stuart, David I.

Subjects
Glycoproteins -- Health aspects, Drug interactions -- Observations, Host-virus relationships -- Observations, Ebola virus -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion (1-7). GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered (8-10). Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein-drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14°C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs., The recent outbreak of EBOV in West Africa, the worst of more than 30 in the past 40 years, comprised more than 28,000 cases and over 11,000 deaths (11). In [...]

Published
2016

39. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author

Tuekprakhon, Aekkachai, primary, Nutalai, Rungtiwa, additional, Dijokaite-Guraliuc, Aiste, additional, Zhou, Daming, additional, Ginn, Helen M., additional, Selvaraj, Muneeswaran, additional, Liu, Chang, additional, Mentzer, Alexander J., additional, Supasa, Piyada, additional, Duyvesteyn, Helen M.E., additional, Das, Raksha, additional, Skelly, Donal, additional, Ritter, Thomas G., additional, Amini, Ali, additional, Bibi, Sagida, additional, Adele, Sandra, additional, Johnson, Sile Ann, additional, Constantinides, Bede, additional, Webster, Hermione, additional, Temperton, Nigel, additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Crook, Derrick, additional, Pollard, Andrew J., additional, Lambe, Teresa, additional, Goulder, Philip, additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Fry, Elizabeth E., additional, Huo, Jiandong, additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Stuart, David I., additional, Screaton, Gavin R., additional, Conlon, Christopher, additional, Deeks, Alexandra, additional, Frater, John, additional, Frending, Lisa, additional, Gardiner, Siobhan, additional, Jämsén, Anni, additional, Jeffery, Katie, additional, Malone, Tom, additional, Phillips, Eloise, additional, Rothwell, Lucy, additional, and Stafford, Lizzie, additional

Published
2022
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40. Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

Author

Nutalai, Rungtiwa, primary, Zhou, Daming, additional, Tuekprakhon, Aekkachai, additional, Ginn, Helen M., additional, Supasa, Piyada, additional, Liu, Chang, additional, Huo, Jiandong, additional, Mentzer, Alexander J., additional, Duyvesteyn, Helen M.E., additional, Dijokaite-Guraliuc, Aiste, additional, Skelly, Donal, additional, Ritter, Thomas G., additional, Amini, Ali, additional, Bibi, Sagida, additional, Adele, Sandra, additional, Johnson, Sile Ann, additional, Constantinides, Bede, additional, Webster, Hermione, additional, Temperton, Nigel, additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Crook, Derrick, additional, Pollard, Andrew J., additional, Lambe, Teresa, additional, Goulder, Philip, additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Mongkolsapaya, Juthathip, additional, Fry, Elizabeth E., additional, Dejnirattisai, Wanwisa, additional, Ren, Jingshan, additional, Stuart, David I., additional, and Screaton, Gavin R., additional

Published
2022
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42. Sample Preparation and Data Collection for High-Speed Fixed-Target Serial Femtosecond Crystallography

Author

Meents, Alke, Meents, Alke, Roedig, Philip, Ginn, Helen M, Pakendorf, Tim, Sutton, Geoff, Harlos, Karl, Walter, Thomas S, Meyer, Jan, Fischer, Pontus, Duman, Ramona, Vartiainen, Ismo, Reime, Bernd, Warmer, Martin, Brewster, Aaron S, Young, Iris D, Clark, Tara Michels, Sauter, Nicholas K, Sikorsky, Marcin, Nelson, Silke, Damiani, Daniel S, Alonso-Mori, Roberto, Ren, Jingshan, Fry, Elizabeth E, David, Christian, Stuart, David I, Wagner, Armin H, Meents, Alke, Meents, Alke, Roedig, Philip, Ginn, Helen M, Pakendorf, Tim, Sutton, Geoff, Harlos, Karl, Walter, Thomas S, Meyer, Jan, Fischer, Pontus, Duman, Ramona, Vartiainen, Ismo, Reime, Bernd, Warmer, Martin, Brewster, Aaron S, Young, Iris D, Clark, Tara Michels, Sauter, Nicholas K, Sikorsky, Marcin, Nelson, Silke, Damiani, Daniel S, Alonso-Mori, Roberto, Ren, Jingshan, Fry, Elizabeth E, David, Christian, Stuart, David I, and Wagner, Armin H

Published
2022

43. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author

Tuekprakhon, Aekkachai, Huo, Jiandong, Nutalai, Rungtiwa, Dijokaite-Guraliuc, Aiste, Zhou, Daming, Ginn, Helen M., Selvaraj, Muneeswaran, Liu, Chang, Mentzer, Alexander J., Supasa, Piyada, Duyvesteyn, Helen M.E., Das, Raksha, Skelly, Donal, Ritter, Thomas G., Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Constantinides, Bede, Webster, Hermione, Temperton, Nigel J., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Crook, Derrick, Pollard, Andrew J., Lambe, Teresa, Goulder, Philip, Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., Screaton, Gavin R., Conlon, Christopher, Deeks, Alexandra, Frater, John, Frending, Lisa, Gardiner, Siobhan, Jämsén, Anni, Jeffery, Katie, Malone, Tom, Phillips, Eloise, Rothwell, Lucy, Stafford, Lizzie, Tuekprakhon, Aekkachai, Huo, Jiandong, Nutalai, Rungtiwa, Dijokaite-Guraliuc, Aiste, Zhou, Daming, Ginn, Helen M., Selvaraj, Muneeswaran, Liu, Chang, Mentzer, Alexander J., Supasa, Piyada, Duyvesteyn, Helen M.E., Das, Raksha, Skelly, Donal, Ritter, Thomas G., Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Constantinides, Bede, Webster, Hermione, Temperton, Nigel J., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Crook, Derrick, Pollard, Andrew J., Lambe, Teresa, Goulder, Philip, Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., Screaton, Gavin R., Conlon, Christopher, Deeks, Alexandra, Frater, John, Frending, Lisa, Gardiner, Siobhan, Jämsén, Anni, Jeffery, Katie, Malone, Tom, Phillips, Eloise, Rothwell, Lucy, and Stafford, Lizzie

Abstract

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

Published
2022

44. Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

Author

Nutalai, Rungtiwa, Zhou, Daming, Tuekprakhon, Aekkachai, Ginn, Helen M., Supasa, Piyada, Liu, Chang, Huo, Jiandong, Mentzer, Alexander J., Duyvesteyn, Helen M.E., Dijokaite-Guraliuc, Aiste, Skelly, Donal, Ritter, Thomas G., Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Constantinides, Bede, Webster, Hermione, Temperton, Nigel J., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Crook, Derrick, Pollard, Andrew J., Lambe, Teresa, Goulder, Philip, Paterson, Neil G., Williams, Mark A., Hall, David R., Mongkolsapaya, Juthathip, Fry, Elizabeth E., Dejnirattisai, Wanwisa, Ren, Jingshan, Stuart, David I., Screaton, Gavin R., Nutalai, Rungtiwa, Zhou, Daming, Tuekprakhon, Aekkachai, Ginn, Helen M., Supasa, Piyada, Liu, Chang, Huo, Jiandong, Mentzer, Alexander J., Duyvesteyn, Helen M.E., Dijokaite-Guraliuc, Aiste, Skelly, Donal, Ritter, Thomas G., Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Constantinides, Bede, Webster, Hermione, Temperton, Nigel J., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Crook, Derrick, Pollard, Andrew J., Lambe, Teresa, Goulder, Philip, Paterson, Neil G., Williams, Mark A., Hall, David R., Mongkolsapaya, Juthathip, Fry, Elizabeth E., Dejnirattisai, Wanwisa, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Abstract

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1 and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site, however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focussed in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains and many show broad reactivity with variants of concern.

Published
2022

45. Hepatitis A virus and the origins of picornaviruses

Author

Wang, Xiangxi, Ren, Jingshan, Gao, Qiang, Hu, Zhongyu, Sun, Yao, Li, Xuemei, Rowlands, David J., Yin, Weidong, Wang, Junzhi, Stuart, David I., Rao, Zihe, and Fry, Elizabeth E.

Subjects
Hepatitis A virus -- Structure, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually (1). It differs radically from other picornaviruses, existing in an enveloped form (2) and being unusually stable, both genetically and physically (3), but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site (4), while structure-based predictions (5) suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses (6,7), and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis (8,9)., HAV is unique among picornaviruses in targeting the liver and continues to be a source of mortality despite a successful vaccine (10). HAV isolates belong to a single serotype (11). [...]

Published
2015
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48. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Author

Dejnirattisai, Wanwisa, primary, Huo, Jiandong, additional, Zhou, Daming, additional, Zahradník, Jiří, additional, Supasa, Piyada, additional, Liu, Chang, additional, Duyvesteyn, Helen M.E., additional, Ginn, Helen M., additional, Mentzer, Alexander J., additional, Tuekprakhon, Aekkachai, additional, Nutalai, Rungtiwa, additional, Wang, Beibei, additional, Dijokaite, Aiste, additional, Khan, Suman, additional, Avinoam, Ori, additional, Bahar, Mohammad, additional, Skelly, Donal, additional, Adele, Sandra, additional, Johnson, Sile Ann, additional, Amini, Ali, additional, Ritter, Thomas G., additional, Mason, Chris, additional, Dold, Christina, additional, Pan, Daniel, additional, Assadi, Sara, additional, Bellass, Adam, additional, Omo-Dare, Nicola, additional, Koeckerling, David, additional, Flaxman, Amy, additional, Jenkin, Daniel, additional, Aley, Parvinder K., additional, Voysey, Merryn, additional, Costa Clemens, Sue Ann, additional, Naveca, Felipe Gomes, additional, Nascimento, Valdinete, additional, Nascimento, Fernanda, additional, Fernandes da Costa, Cristiano, additional, Resende, Paola Cristina, additional, Pauvolid-Correa, Alex, additional, Siqueira, Marilda M., additional, Baillie, Vicky, additional, Serafin, Natali, additional, Kwatra, Gaurav, additional, Da Silva, Kelly, additional, Madhi, Shabir A., additional, Nunes, Marta C., additional, Malik, Tariq, additional, Openshaw, Peter J.M., additional, Baillie, J. Kenneth, additional, Semple, Malcolm G., additional, Townsend, Alain R., additional, Huang, Kuan-Ying A., additional, Tan, Tiong Kit, additional, Carroll, Miles W., additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Constantinides, Bede, additional, Webster, Hermione, additional, Crook, Derrick, additional, Pollard, Andrew J., additional, Lambe, Teresa, additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Fry, Elizabeth E., additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Schreiber, Gideon, additional, Stuart, David I., additional, Screaton, Gavin R., additional, Conlon, Christopher, additional, Deeks, Alexandra S., additional, Frater, John, additional, Frending, Lisa, additional, Gardiner, Siobhan, additional, Jämsén, Anni, additional, Jeffery, Katie, additional, Malone, Tom, additional, Phillips, Eloise, additional, Rothwell, Lucy, additional, Stafford, Lizzie, additional, Baillie, J Kenneth, additional, Openshaw, Peter JM., additional, Carson, Gail, additional, Alex, Beatrice, additional, Andrikopoulos, Petros, additional, Bach, Benjamin, additional, Barclay, Wendy S., additional, Bogaert, Debby, additional, Chand, Meera, additional, Chechi, Kanta, additional, Cooke, Graham S., additional, da Silva Filipe, Ana, additional, de Silva, Thushan, additional, Docherty, Annemarie B., additional, dos Santos Correia, Gonçalo, additional, Dumas, Marc-Emmanuel, additional, Dunning, Jake, additional, Fletcher, Tom, additional, Green, Christoper A., additional, Greenhalf, William, additional, Griffin, Julian L., additional, Gupta, Rishi K., additional, Harrison, Ewen M., additional, Hiscox, Julian A., additional, Wai Ho, Antonia Ying, additional, Horby, Peter W., additional, Ijaz, Samreen, additional, Khoo, Saye, additional, Law, Andrew, additional, Lewis, Matthew R., additional, Liggi, Sonia, additional, Lim, Wei Shen, additional, Maslen, Lynn, additional, Merson, Laura, additional, Meynert, Alison M., additional, Moore, Shona C., additional, Noursadeghi, Mahdad, additional, Olanipekun, Michael, additional, Osagie, Anthonia, additional, Palmarini, Massimo, additional, Palmieri, Carlo, additional, Paxton, William A., additional, Pollakis, Georgios, additional, Price, Nicholas, additional, Rambaut, Andrew, additional, Robertson, David L., additional, Russell, Clark D., additional, Sancho-Shimizu, Vanessa, additional, Sands, Caroline J., additional, Scott, Janet T., additional, Sigfrid, Louise, additional, Solomon, Tom, additional, Sriskandan, Shiranee, additional, Stuart, David, additional, Summers, Charlotte, additional, Swann, Olivia V., additional, Takats, Zoltan, additional, Takis, Panteleimon, additional, Tedder, Richard S., additional, Thompson, AA Roger, additional, Thomson, Emma C., additional, Thwaites, Ryan S., additional, Turtle, Lance CW., additional, Zambon, Maria, additional, Hardwick, Hayley, additional, Donohue, Chloe, additional, Griffiths, Fiona, additional, Oosthuyzen, Wilna, additional, Donegan, Cara, additional, Spencer, Rebecca G., additional, Norman, Lisa, additional, Pius, Riinu, additional, Drake, Thomas M., additional, Fairfield, Cameron J., additional, Knight, Stephen R., additional, Mclean, Kenneth A., additional, Murphy, Derek, additional, Shaw, Catherine A., additional, Dalton, Jo, additional, Girvan, Michelle, additional, Saviciute, Egle, additional, Roberts, Stephanie, additional, Harrison, Janet, additional, Marsh, Laura, additional, Connor, Marie, additional, Halpin, Sophie, additional, Jackson, Clare, additional, Gamble, Carrol, additional, Plotkin, Daniel, additional, Lee, James, additional, Leeming, Gary, additional, Wham, Murray, additional, Clohisey, Sara, additional, Hendry, Ross, additional, Scott-Brown, James, additional, Shaw, Victoria, additional, McDonald, Sarah E., additional, Keating, Seán, additional, Ahmed, Katie A., additional, Armstrong, Jane A., additional, Ashworth, Milton, additional, Asiimwe, Innocent G., additional, Bakshi, Siddharth, additional, Barlow, Samantha L., additional, Booth, Laura, additional, Brennan, Benjamin, additional, Bullock, Katie, additional, Catterall, Benjamin WA., additional, Clark, Jordan J., additional, Clarke, Emily A., additional, Cole, Sarah, additional, Cooper, Louise, additional, Cox, Helen, additional, Davis, Christopher, additional, Dincarslan, Oslem, additional, Dunn, Chris, additional, Dyer, Philip, additional, Elliott, Angela, additional, Evans, Anthony, additional, Finch, Lorna, additional, Fisher, Lewis WS., additional, Foster, Terry, additional, Garcia-Dorival, Isabel, additional, Gunning, Philip, additional, Hartley, Catherine, additional, Jensen, Rebecca L., additional, Jones, Christopher B., additional, Jones, Trevor R., additional, Khandaker, Shadia, additional, King, Katharine, additional, Kiy, Robyn T., additional, Koukorava, Chrysa, additional, Lake, Annette, additional, Lant, Suzannah, additional, Latawiec, Diane, additional, Lavelle-Langham, Lara, additional, Lefteri, Daniella, additional, Lett, Lauren, additional, Livoti, Lucia A., additional, Mancini, Maria, additional, McDonald, Sarah, additional, McEvoy, Laurence, additional, McLauchlan, John, additional, Metelmann, Soeren, additional, Miah, Nahida S., additional, Middleton, Joanna, additional, Mitchell, Joyce, additional, Murphy, Ellen G., additional, Penrice-Randal, Rebekah, additional, Pilgrim, Jack, additional, Prince, Tessa, additional, Reynolds, Will, additional, Ridley, P. Matthew, additional, Sales, Debby, additional, Shaw, Victoria E., additional, Shears, Rebecca K., additional, Small, Benjamin, additional, Subramaniam, Krishanthi S., additional, Szemiel, Agnieska, additional, Taggart, Aislynn, additional, Tanianis-Hughes, Jolanta, additional, Thomas, Jordan, additional, Trochu, Erwan, additional, van Tonder, Libby, additional, Wilcock, Eve, additional, Zhang, J. Eunice, additional, Flaherty, Lisa, additional, Maziere, Nicole, additional, Cass, Emily, additional, Carracedo, Alejandra Doce, additional, Carlucci, Nicola, additional, Holmes, Anthony, additional, Massey, Hannah, additional, Murphy, Lee, additional, McCafferty, Sarah, additional, Clark, Richard, additional, Fawkes, Angie, additional, Morrice, Kirstie, additional, Maclean, Alan, additional, Wrobel, Nicola, additional, Donnelly, Lorna, additional, Coutts, Audrey, additional, Hafezi, Katarzyna, additional, MacGillivray, Louise, additional, Gilchrist, Tammy, additional, Adeniji, Kayode, additional, Agranoff, Daniel, additional, Agwuh, Ken, additional, Ail, Dhiraj, additional, Aldera, Erin L., additional, Alegria, Ana, additional, Allen, Sam, additional, Angus, Brian, additional, Ashish, Abdul, additional, Atkinson, Dougal, additional, Bari, Shahedal, additional, Barlow, Gavin, additional, Barnass, Stella, additional, Barrett, Nicholas, additional, Bassford, Christopher, additional, Basude, Sneha, additional, Baxter, David, additional, Beadsworth, Michael, additional, Bernatoniene, Jolanta, additional, Berridge, John, additional, Berry, Colin, additional, Best, Nicola, additional, Bothma, Pieter, additional, Chadwick, David, additional, Brittain-Long, Robin, additional, Bulteel, Naomi, additional, Burden, Tom, additional, Burtenshaw, Andrew, additional, Caruth, Vikki, additional, Chambler, Duncan, additional, Chee, Nigel, additional, Child, Jenny, additional, Chukkambotla, Srikanth, additional, Clark, Tom, additional, Collini, Paul, additional, Cosgrove, Catherine, additional, Cupitt, Jason, additional, Cutino-Moguel, Maria-Teresa, additional, Dark, Paul, additional, Dawson, Chris, additional, Dervisevic, Samir, additional, Donnison, Phil, additional, Douthwaite, Sam, additional, Drummond, Andrew, additional, DuRand, Ingrid, additional, Dushianthan, Ahilanadan, additional, Dyer, Tristan, additional, Evans, Cariad, additional, Eziefula, Chi, additional, Fegan, Chrisopher, additional, Finn, Adam, additional, Fullerton, Duncan, additional, Garg, Sanjeev, additional, Garg, Atul, additional, Gkrania-Klotsas, Effrossyni, additional, Godden, Jo, additional, Goldsmith, Arthur, additional, Graham, Clive, additional, Hardy, Elaine, additional, Hartshorn, Stuart, additional, Harvey, Daniel, additional, Havalda, Peter, additional, Hawcutt, Daniel B., additional, Hobrok, Maria, additional, Hodgson, Luke, additional, Hormis, Anil, additional, Jacobs, Michael, additional, Jain, Susan, additional, Jennings, Paul, additional, Kaliappan, Agilan, additional, Kasipandian, Vidya, additional, Kegg, Stephen, additional, Kelsey, Michael, additional, Kendall, Jason, additional, Kerrison, Caroline, additional, Kerslake, Ian, additional, Koch, Oliver, additional, Koduri, Gouri, additional, Koshy, George, additional, Laha, Shondipon, additional, Laird, Steven, additional, Larkin, Susan, additional, Leiner, Tamas, additional, Lillie, Patrick, additional, Limb, James, additional, Linnett, Vanessa, additional, Little, Jeff, additional, Lyttle, Mark, additional, MacMahon, Michael, additional, MacNaughton, Emily, additional, Mankregod, Ravish, additional, Masson, Huw, additional, Matovu, Elijah, additional, McCullough, Katherine, additional, McEwen, Ruth, additional, Meda, Manjula, additional, Mills, Gary, additional, Minton, Jane, additional, Mirfenderesky, Mariyam, additional, Mohandas, Kavya, additional, Mok, Quen, additional, Moon, James, additional, Moore, Elinoor, additional, Morgan, Patrick, additional, Morris, Craig, additional, Mortimore, Katherine, additional, Moses, Samuel, additional, Mpenge, Mbiye, additional, Mulla, Rohinton, additional, Murphy, Michael, additional, Nagel, Megan, additional, Nagarajan, Thapas, additional, Nelson, Mark, additional, Norris, Lillian, additional, O’Shea, Matthew K., additional, Otahal, Igor, additional, Ostermann, Marlies, additional, Pais, Mark, additional, Panchatsharam, Selva, additional, Papakonstantinou, Danai, additional, Paraiso, Hassan, additional, Patel, Brij, additional, Pattison, Natalie, additional, Pepperell, Justin, additional, Peters, Mark, additional, Phull, Mandeep, additional, Pintus, Stefania, additional, Pooni, Jagtur Singh, additional, Planche, Tim, additional, Post, Frank, additional, Price, David, additional, Prout, Rachel, additional, Rae, Nikolas, additional, Reschreiter, Henrik, additional, Reynolds, Tim, additional, Richardson, Neil, additional, Roberts, Mark, additional, Roberts, Devender, additional, Rose, Alistair, additional, Rousseau, Guy, additional, Ruge, Bobby, additional, Ryan, Brendan, additional, Saluja, Taranprit, additional, Schmid, Matthias L., additional, Shah, Aarti, additional, Shanmuga, Prad, additional, Sharma, Anil, additional, Shawcross, Anna, additional, Sizer, Jeremy, additional, Shankar-Hari, Manu, additional, Smith, Richard, additional, Snelson, Catherine, additional, Spittle, Nick, additional, Staines, Nikki, additional, Stambach, Tom, additional, Stewart, Richard, additional, Subudhi, Pradeep, additional, Szakmany, Tamas, additional, Tatham, Kate, additional, Thomas, Jo, additional, Thompson, Chris, additional, Thompson, Robert, additional, Tridente, Ascanio, additional, Tupper-Carey, Darell, additional, Twagira, Mary, additional, Vallotton, Nick, additional, Vancheeswaran, Rama, additional, Vincent-Smith, Lisa, additional, Visuvanathan, Shico, additional, Vuylsteke, Alan, additional, Waddy, Sam, additional, Wake, Rachel, additional, Walden, Andrew, additional, Welters, Ingeborg, additional, Whitehouse, Tony, additional, Whittaker, Paul, additional, Whittington, Ashley, additional, Papineni, Padmasayee, additional, Wijesinghe, Meme, additional, Williams, Martin, additional, Wilson, Lawrence, additional, Winchester, Stephen, additional, Wiselka, Martin, additional, Wolverson, Adam, additional, Wootton, Daniel G., additional, Workman, Andrew, additional, Yates, Bryan, additional, and Young, Peter, additional

Published
2022
Full Text
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49. Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Author

Dejnirattisai, Wanwisa, Huo, Jiandong, Zhou, Daming, Zahradník, Jiří, Supasa, Piyada, Liu, Chang, Duyvesteyn, Helen M.E., Ginn, Helen M., Mentzer, Alexander J., Tuekprakhon, Aekkachai, Nutalai, Rungtiwa, Wang, Beibei, Dijokaite, Aiste, Khan, Suman, Avinoam, Ori, Bahar, Mohammad, Skelly, Donal, Adele, Sandra, Johnson, Sile Ann, Amini, Ali, Ritter, Thomas, Mason, Chris, Dold, Christina, Pan, Daniel, Assadi, Sara, Bellass, Adam, Omo-Dare, Nikki, Koeckerling, David, Flaxman, Amy, Jenkin, Daniel, Aley, Parvinder K, Voysey, Merryn, Clemens, Sue Ann Costa, Naveca, Felipe Gomes, Nascimento, Valdinete, Nascimento, Fernanda, Fernandes da Costa, Cristiano, Resende, Paola Cristina, Pauvolid-Correa, Alex, Siqueira, Marilda M., Baillie, Vicky, Serafin, Natali, Ditse, Zanele, Da Silva, Kelly, Madhi, Shabir, Nunes, Marta C, Malik, Tariq, Openshaw, Peter JM, Baillie, J Kenneth, Semple, Malcolm G, Townsend, Alain R, Huang, Kuan-Ying A., Tan, Tiong Kit, Carroll, Miles W., Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J., Constantinides, Bede, Webster, Hermione, Crook, Derrick, Pollard, Andrew J, Lambe, Teresa, Paterson, Neil G., Williams, Mark A., Hall, David R., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Schreiber, Gideon, Stuart, David I., and Screaton, Gavin R

Subjects
Article
Abstract

SummaryOn the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

Published
2021

50. Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2

Author

Huang, Kuan-Ying A., primary, Zhou, Daming, additional, Tan, Tiong Kit, additional, Chen, Charles, additional, Duyvesteyn, Helen M. E., additional, Zhao, Yuguang, additional, Ginn, Helen M., additional, Qin, Ling, additional, Rijal, Pramila, additional, Schimanski, Lisa, additional, Donat, Robert, additional, Harding, Adam, additional, Gilbert-Jaramillo, Javier, additional, James, William, additional, Tree, Julia A., additional, Buttigieg, Karen, additional, Carroll, Miles, additional, Charlton, Sue, additional, Lien, Chia-En, additional, Lin, Meei-Yun, additional, Chen, Cheng-Pin, additional, Cheng, Shu-Hsing, additional, Chen, Xiaorui, additional, Lin, Tzou-Yien, additional, Fry, Elizabeth E., additional, Ren, Jingshan, additional, Ma, Che, additional, Townsend, Alain R., additional, and Stuart, David I., additional

Published
2022
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