160 results on '"Mongkolsapaya J"'
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2. The acquired immune response in dengue virus infection.
- Author
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Screaton, G. R., primary and Mongkolsapaya, J., additional
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- 2014
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3. Cryo-EM structure of mature Spondweni virus
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Renner, M., primary, Dejnirattisai, W., additional, Carrique, L., additional, Serna Martin, I., additional, Karia, D., additional, Ilca, S.L., additional, Ho, S.F., additional, Kotecha, A., additional, Keown, J.R., additional, Mongkolsapaya, J., additional, Screaton, G.R., additional, and Grimes, J.M., additional
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- 2021
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4. Cryo-EM structure of immature Spondweni virus
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Renner, M., primary, Dejnirattisai, W., additional, Carrique, L., additional, Serna Martin, I., additional, Karia, D., additional, Ilca, S.L., additional, Ho, S.F., additional, Kotecha, A., additional, Keown, J.R., additional, Mongkolsapaya, J., additional, Screaton, G.R., additional, and Grimes, J.M., additional
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- 2021
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5. Cryo-EM structure of trimeric prME spike of Spondweni virus
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Renner, M., primary, Dejnirattisai, W., additional, Carrique, L., additional, Serna Martin, I., additional, Karia, D., additional, Ilca, S.L., additional, Ho, S.F., additional, Kotecha, A., additional, Keown, J.R., additional, Mongkolsapaya, J., additional, Screaton, G.R., additional, and Grimes, J.M., additional
- Published
- 2021
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6. Cryo-EM structure of Spondweni virus prME
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Renner, M., primary, Dejnirattisai, W., additional, Carrique, L., additional, Serna Martin, I., additional, Karia, D., additional, Ilca, S.L., additional, Ho, S.F., additional, Kotecha, A., additional, Keown, J.R., additional, Mongkolsapaya, J., additional, Screaton, G.R., additional, and Grimes, J.M., additional
- Published
- 2021
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- View/download PDF
7. Cryo-EM structure of mature Dengue virus 2 at 3.1 angstrom resolution
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Renner, M., primary, Dejnirattisai, W., additional, Carrique, L., additional, Serna Martin, I., additional, Karia, D., additional, Ilca, S.L., additional, Ho, S.F., additional, Kotecha, A., additional, Keown, J.R., additional, Mongkolsapaya, J., additional, Screaton, G.R., additional, and Grimes, J.M., additional
- Published
- 2021
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8. Complement alternative pathway genetic variation and Dengue infection in the Thai population
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Kraivong, R., Vasanawathana, S., Limpitikul, W., Malasit, P., Tangthawornchaikul, N., Botto, M., Screaton, G. R., Mongkolsapaya, J., and Pickering, M. C.
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- 2013
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9. Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors
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López-Camacho, C, Abbink, P, Larocca, R, Dejnirattisai, W, Boyd, M, Badamchi-Zadeh, A, Wallace, Z, Doig, J, Velazquez, R, Neto, R, Coelho, D, Kim, Y, Donald, C, Owsianka, A, De Lorenzo, G, Kohl, A, Gilbert, S, Dorrell, L, Mongkolsapaya, J, Patel, A, Screaton, G, Barouch, D, Hill, A, Reyes-Sandoval, A, Medical Research Council (MRC), and Wellcome Trust
- Subjects
Pan troglodytes ,Science ,Genetic Vectors ,Article ,Adenoviridae ,Mice ,Immunogenicity, Vaccine ,Protein Domains ,Viral Envelope Proteins ,MD Multidisciplinary ,Animals ,Humans ,lcsh:Science ,Antigens, Viral ,Mice, Inbred BALB C ,Mice, Inbred ICR ,Zika Virus Infection ,Viral Vaccines ,Zika Virus ,Dengue Virus ,Antibody-Dependent Enhancement ,Disease Models, Animal ,Drug Design ,Female ,lcsh:Q - Abstract
Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments., Zika virus (ZIKV) is an emerging global health issue, but currently no licensed vaccine achieves lasting protective immunity. Here the authors show that a ZIKV vaccine containing the envelop protein without the transmembrane domain and the precursor membrane protein can provide effective protection in mouse models.
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- 2018
10. Death receptors and their role in immune function
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Screaton, G R., Mongkolsapaya, J., Xu, X., Simon, K., and Dasgupta, R.
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- 1999
11. Longitudinal analysis of antibody cross-neutralization following zika virus and dengue virus infection in Asia and the Americas
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Screaton, G., De Silva, A.D., Schildhauer, S., Balmaseda, A., Puerta-Guardo, H., Harris, E., Tissera, H., Jadi, R., Mongkolsapaya, J., Supasa, P., Malasit, P., Katzelnick, L.C., Montoya, M., Vasanawathana, S., De Silva, A.M., Dejnirattisai, W., and Collins, M.
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viruses ,virus diseases ,biochemical phenomena, metabolism, and nutrition - Abstract
Background The 4 dengue virus serotypes (DENV1-4) and Zika virus (ZIKV) are related mosquito-borne flaviviruses of major importance globally. While monoclonal antibodies and plasma from DENV-immune donors can neutralize or enhance ZIKV in vitro and in small-animal models, and vice versa, the extent, duration, and significance of cross-reactivity in humans remains unknown, particularly in flavivirus-endemic regions. Methods We studied neutralizing antibodies to ZIKV and DENV1-4 in longitudinal serologic specimens collected through 3 years after infection from people in Latin America and Asia with laboratory-confirmed DENV infections. We also evaluated neutralizing antibodies to ZIKV and DENV1-4 in patients with Zika through 6 months after infection. Results In patients with Zika, the highest neutralizing antibody titers were to ZIKV, with low-level cross-reactivity to DENV1-4 that was greater in DENV-immune individuals. We found that, in primary and secondary DENV infections, neutralizing antibody titers to ZIKV were markedly lower than to the infecting DENV and heterologous DENV serotypes. Cross-neutralization was greatest in early convalescence, then ZIKV neutralization decreased, remaining at low levels over time. Conclusions Patterns of antibody cross-neutralization suggest that ZIKV lies outside the DENV serocomplex. Neutralizing antibody titers can distinguish ZIKV from DENV infections when all viruses are analyzed simultaneously. These findings have implications for understanding natural immunity and vaccines.
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- 2018
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12. DIFFERENTATION AND ACTIVATION ANTIGENS ON CD8 T CELLS: TC-4-06
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Mongkolsapaya, J, Callan, M F C, and McMichael, A J
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- 1996
13. Differentiation and activation antigens on CD8 T cells
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Mongkolsapaya, J, Callan, MFC, and Mcmichael, AJ
- Published
- 2016
14. An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection (vol 85, pg 410, 2011)
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Midgley, CM, Bajwa-Joseph, M, Vasanawathana, S, Limpitikul, W, Wills, B, Flanagan, A, Waiyaiya, E, Tran, HB, Cowper, AE, Chotiyarnwong, P, Grimes, JM, Yoksan, S, Malasit, P, Simmons, CP, Mongkolsapaya, J, and Screaton, GR
- Published
- 2016
15. Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation
- Author
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Mongkolsapaya, J, Grimes, JM, Chen, N, Xu, XN, Stuart, DI, Jones, EY, and Screaton, GR
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TRAIL, an apoptosis inducing ligand, has at least four cell surface receptors including the death receptor DR5. Here we report the crystal structure at 2.2 A resolution of a complex between TRAIL and the extracellular region of DR5. TRAIL forms a central homotrimer around which three DR5 molecules bind. Radical differences in the surface charge of the ligand, together with variation in the alignment of the two receptor domains confer specificity between members of these ligand and receptor families. The existence of a switch mechanism allowing variation in receptor domain alignment may mean that it is possible to engineer receptors with multiple specificities by exploiting contact positions unique to individual receptor-ligand pairs.
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- 2016
16. MAIT cells are activated during human viral infections
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Van Wilgenburg, B, Klenerman, P, Willberg, C, Kurioka, A, Ramamurthy, N, Leng, T, De Lara, C, Scherwitzl, I, Hutchinson, EC, Kuclike, C, Cole, S, Vasanawathana, S, Limpitikul, Malasit, P, Young, D, Denney, L, Moore, MD, Fabris, P, Giordani, MT, Oo, YH, Laidlaw, SM, Dustin, LB, Ho, LP, Thompson, FM, Mongkolsapaya, J, and Screaton, GR
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Adult ,Male ,Virus Diseases ,Leukocytes, Mononuclear ,Cytokines ,Humans ,Female ,Lymphocyte Activation ,Cells, Cultured ,Coculture Techniques ,Mucosal-Associated Invariant T Cells ,Article - Abstract
Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation—driving cytokine release and Granzyme B upregulation—is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology., Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.
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- 2015
17. Complement alternative pathway genetic variation and Dengue infection in the Thai population
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Kraivong, R, Vasanawathana, S, Limpitikul, W, Malasit, P, Tangthawornchaikul, N, Botto, M, Screaton, GR, Mongkolsapaya, J, and Pickering, MC
- Published
- 2013
18. Structural flexibility and ligand-binding characteristics of the macrophage dengue virus receptor CLEC5A
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Watson, A, Lebedev, A, Hall, B, Fenton-May, A, Vagin, A, Dejnirattisai, W, Felce, J, Mongkolsapaya, J, Palma, A, Liu, Y, Feizi, T, Screaton, G, Murshudov, G, and O'Callaghan, C
- Published
- 2011
19. Structural Flexibility of the Macrophage Dengue Virus Receptor CLEC5A: IMPLICATIONS FOR LIGAND BINDING AND SIGNALING*
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Watson, AA, Lebedev, AA, Hall, BA, Fenton-May, AE, Vagin, AA, Dejnirattisai, W, Felce, J, Mongkolsapaya, J, Palma, AS, Liu, Y, Feizi, T, Screaton, GR, Murshudov, GN, and O'Callaghan, CA
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Macrophages ,Membrane Proteins ,Receptors, Cell Surface ,Dengue Virus ,Crystallography, X-Ray ,Protein Structure, Secondary ,Dengue ,Structure-Activity Relationship ,HEK293 Cells ,Protein Structure and Folding ,Humans ,Lectins, C-Type ,Protein Multimerization ,Protein Structure, Quaternary ,Adaptor Proteins, Signal Transducing - Abstract
The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. The binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule DAP12, stimulating proinflammatory cytokine release. We have crystallized an informative ensemble of CLEC5A structural conformers at 1.9-Å resolution and demonstrate how an on-off extension to a β-sheet acts as a binary switch regulating the flexibility of the molecule. This structural information together with molecular dynamics simulations suggests a mechanism whereby extracellular events may be transmitted through the membrane and influence DAP12 signaling. We demonstrate that CLEC5A is homodimeric at the cell surface and binds to dengue virus serotypes 1-4. We used blotting experiments, surface analyses, glycan microarray, and docking studies to investigate the ligand binding potential of CLEC5A with particular respect to dengue virus. This study provides a rational foundation for understanding the dengue virus-macrophage interaction and the role of CLEC5A in dengue virus-induced lethal disease.
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- 2011
20. Complement alternative pathway genetic variation and D engue infection in the T hai population
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Kraivong, R., primary, Vasanawathana, S., additional, Limpitikul, W., additional, Malasit, P., additional, Tangthawornchaikul, N., additional, Botto, M., additional, Screaton, G. R., additional, Mongkolsapaya, J., additional, and Pickering, M. C., additional
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- 2013
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21. Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL
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Mongkolsapaya J, Ae, Cowper, Xn, Xu, Morris G, Aj, Mcmichael, Ji, Bell, and Gavin Screaton
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Membrane Glycoproteins ,Sequence Homology, Amino Acid ,Tumor Necrosis Factor-alpha ,Molecular Sequence Data ,Membrane Proteins ,Apoptosis ,TNF-Related Apoptosis-Inducing Ligand ,Humans ,Tissue Distribution ,Amino Acid Sequence ,Receptors, Immunologic ,Apoptosis Regulatory Proteins ,Sequence Alignment ,Repetitive Sequences, Nucleic Acid - Abstract
Apoptosis can be triggered by the engagement of cell surface receptors by their ligands. A growing number of receptors belonging to the TNF receptor family have been identified that contain a conserved cytoplasmic death domain. These include Fas, TNF-R1, lymphocyte-associated receptor of death (LARD), DR4, and TNF-related apoptosis-inducing ligand receptor inducer of cell killing-2 (TRICK2). The latter two are receptors for the cytotoxic ligand TNF-related apoptosis-inducing ligand (TRAIL), and one of the paradoxes raised by the cloning of these molecules was why do most cells not die upon contact with the widely expressed TRAIL molecule? This is a particular problem for lymphocytes that express DR4 and TRICK2 and are in constant circulation through TRAIL-expressing tissues. We have cloned LIT (lymphocyte inhibitor of TRAIL), which lacks a death domain. LIT is expressed predominantly on PBL, where it can competitively inhibit TRAIL-induced apoptosis through DR4/TRICK2, and may function to modulate lymphocyte sensitivity to TRAIL.
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- 1998
22. Structure of Dengue virus DIII in complex with Fab 2H12
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Midgley, C.M., primary, Flanagan, A., additional, Mongkolsapaya, J., additional, Grimes, J.M., additional, and Screaton, G.R., additional
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- 2012
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23. Structure of Dengue virus strain 4 DIII in complex with Fab 2H12
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Midgley, C.M., primary, Flanagan, A., additional, Mongkolsapaya, J., additional, Grimes, J.M., additional, and Screaton, G.R., additional
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- 2012
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24. Crystal structure of trail-DR5 complex
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Mongkolsapaya, J., primary, Grimes, J.M., additional, Stuart, D.I., additional, Jones, E.Y., additional, and Screaton, G.R., additional
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- 1999
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25. [Untitled]
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Siridechadilok, B, Gomutsukhavadee, M, Sawaengpol, T, Sangiambut, S, Puttikhunt, C, Chin-inmanu, K, Suriyaphol, P, Malasit, P, Screaton, G, and Mongkolsapaya, J
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viruses ,Immunology ,Mutant ,Computational biology ,Biology ,Microbiology ,Virus ,03 medical and health sciences ,Viral genetics ,Virology ,RNA Viruses ,Genomic library ,Throughput (business) ,Gene Library ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,RNA ,RNA virus ,biology.organism_classification ,Phenotype ,Genome Replication and Regulation of Viral Gene Expression ,Insect Science ,RNA, Viral ,Genetic Engineering - Abstract
Here we present an approach that advances the throughput of a genetic analysis of a positive-sense RNA virus by simplifying virus construction. It enabled comprehensive dissection of a complex, multigene phenotype through rapid derivation of a large number of chimeric viruses and construction of a mutant library directly from a virus pool. The versatility of the approach described here expands the applicability of diverse genetic approaches to study these viruses.
26. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites.
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Malasit, P, primary, Warrell, D A, additional, Chanthavanich, P, additional, Viravan, C, additional, Mongkolsapaya, J, additional, Singhthong, B, additional, and Supich, C, additional
- Published
- 1986
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27. Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike.
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Duyvesteyn HME, Dijokaite-Guraliuc A, Liu C, Supasa P, Kronsteiner B, Jeffery K, Stafford L, Klenerman P, Dunachie SJ, Mongkolsapaya J, Fry EE, Ren J, Stuart DI, and Screaton GR
- Abstract
BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an "all-down" conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. D.I.S. consults for AstraZeneca. Oxford University holds intellectual property related to SARS-CoV-2 mAbs discovered in G.R.S.’s laboratory. S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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28. Immunogenicity of Abdala COVID-19 vaccine in Vietnamese people after primary and booster vaccinations: A prospective observational study in Vietnam.
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Thanh TT, Tu NTK, Nguyet LA, Thuy CT, Thuan NLT, Ny NTH, Nhu LNT, Thanh LK, Hong NTT, Anh NT, Truong NT, Chau NVV, Yen LM, Van E P, Thuong NP, Van Truc N, Trung PH, Yap WC, Pandey R, Yee S, Weng R, Mongkolsapaya J, Dejnirattisai W, Hamers RL, Chantratita N, Screaton G, Dunachie SJ, Jones EY, Stuart DI, Dung NT, Thwaites G, Wang LF, Tan CW, and Tan LV
- Abstract
Objectives: We studied the immunogenicity after primary and booster vaccinations of the Abdala COVID-19 vaccine, a receptor-binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants and SARS-CoV-1., Methods: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks after the booster dose. We measured anti-nucleocapsid, anti-spike, and neutralizing antibodies against SARS-CoV-2 and assessed the cross-neutralization against 14 SARS-CoV-2 variants and SARS-CoV-1. Complementary antibody data came from Vietnamese health care workers fully vaccinated with ChAdOx1-S., Results: After primary vaccination, anti-spike antibody and neutralizing antibodies were detectable in 98.4% and 87% of 251 study participants, respectively, with neutralizing antibody titers similar to that induced by ChAdOx1-S vaccine. Antibody responses after a homologous (Abdala COVID-19) or heterologous (messenger RNA BNT162b2) booster could neutralize 14 SARS-CoV-2 variants (including Omicron) and SARS-CoV-1., Conclusions: Abdala COVID-19 vaccine is immunogenic in Vietnamese people. Enhanced antibody response after a booster dose could cross-neutralize 14 SARS-CoV-2 variants and SARS-CoV-1. Our results have added to the growing body of knowledge about the contribution of protein subunit vaccine platforms to pandemic control., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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29. The alteration of NK cells phenotypes related to the functions and dengue disease outcomes.
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Taechasan N, Scherwitzl I, Supasa P, Dejnirattisai W, Sriruksa K, Limpitikul W, Malasit P, Screaton GR, Mongkolsapaya J, and Duangchinda T
- Subjects
- Humans, Child, Male, Female, Interleukin-15 immunology, Lymphocyte Activation, Interleukin-18 immunology, Natural Cytotoxicity Triggering Receptor 3 immunology, Child, Preschool, Dengue immunology, Dengue virology, Severe Dengue immunology, Severe Dengue virology, Adolescent, CD56 Antigen immunology, Interferon Type I immunology, Killer Cells, Natural immunology, Interleukin-12 immunology, Phenotype, Dendritic Cells immunology, Dengue Virus immunology, Interferon-gamma immunology
- Abstract
Natural killer cells (NK cells) are the front line of immune cells to combat pathogens and able to influence the subsequent adaptive immune responses. One of the factors contributing to pathogenesis in dengue hemorrhagic fever (DHF) disease is aberrant immune activation during early phase of infection. This study explored the profile of NK cells in dengue infected pediatric patients with different degrees of disease severity. DHF patients contained higher frequency of activated NK cells but lower ratio of CD56
dim :CD56bright NK subsets. Activated NK cells exhibited alterations in several NK receptors. Interestingly, the frequencies of NKp30 expressing activated NK cells were more pronounced in dengue fever (DF) than in DHF pediatric patients. In vitro functional analysis indicated that degranulation of NK cells in responding to dengue infected dendritic cells (DCs) required cell-cell contact and type I IFNs. Meanwhile, Interferon gamma (IFN-γ) production initially required cell-cell contact and type I IFNs followed by Interleukin-12 (IL-12), Interleukin-15 (IL-15) and Interleukin-18 (IL-18) resulting in the amplification of IFN-γ producing NK cells over time. This study highlighted the complexity and the factors influencing NK cells responses to dengue virus. Degree of activation, phenotypes of activated cells and the crosstalk between NK cells and other immune cells, could modulate the outcome of NK cells function in the dengue disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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30. AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults.
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Cai Y, Diallo S, Rosenthal K, Ren K, Flores DJ, Dippel A, Oganesyan V, van Dyk N, Chen X, Cantu E, Choudhary R, Sulikowski M, Adissu H, Chawla B, Kar S, Liu C, Dijokaite-Guraliuc A, Mongkolsapaya J, Rajan S, Loo YM, Beavon R, Webber C, Chang LJ, Thomas S, Clegg L, Zhang H, Screaton GR, Philbin N, Harre M, Selim A, Martinez-Alier N, Uriel A, Cohen TS, Perez JL, Esser MT, Blair W, and Francica JR
- Subjects
- Animals, Humans, Cricetinae, COVID-19 Drug Treatment, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacokinetics, Mesocricetus, Female, Male, Adult, Antibodies, Viral immunology, Mutation genetics, Antibodies, Monoclonal, Angiotensin-Converting Enzyme 2 metabolism, Viral Load drug effects, SARS-CoV-2 drug effects, COVID-19 virology, Antibodies, Neutralizing immunology, Spike Glycoprotein, Coronavirus metabolism
- Abstract
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2-neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds to the back left shoulder of the SARS-CoV-2 spike protein receptor binding domain and prevents interaction with the human angiotensin-converting enzyme 2 receptor. AZD3152 potently neutralized a broad panel of pseudovirus variants, including the currently dominant Omicron variant JN.1 but has reduced potency against XBB subvariants containing F456L. In vitro studies confirmed F456L resistance and additionally identified T415I and K458E as escape mutations. In a Syrian hamster challenge model, prophylactic administration of AZD3152 protected hamsters from weight loss and inflammation-related lung pathologies and reduced lung viral load. In the phase 1 sentinel safety cohort of the ongoing SUPERNOVA study (ClinicalTrials.gov: NCT05648110), a single 600-mg intramuscular injection of AZD5156 (containing 300 mg each of AZD3152 and cilgavimab) was well tolerated in adults through day 91. Observed serum concentrations of AZD3152 through day 91 were similar to those observed with cilgavimab and consistent with predictions for AZD7442, a SARS-CoV-2-neutralizing antibody combination of cilgavimab and tixagevimab, in a population pharmacokinetic model. On the basis of its pharmacokinetic characteristics, AZD3152 is predicted to provide durable protection against symptomatic coronavirus disease 2019 caused by susceptible SARS-CoV-2 variants, such as JN.1, in humans.
- Published
- 2024
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31. A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity.
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Liu C, Zhou D, Dijokaite-Guraliuc A, Supasa P, Duyvesteyn HME, Ginn HM, Selvaraj M, Mentzer AJ, Das R, de Silva TI, Ritter TG, Plowright M, Newman TAH, Stafford L, Kronsteiner B, Temperton N, Lui Y, Fellermeyer M, Goulder P, Klenerman P, Dunachie SJ, Barton MI, Kutuzov MA, Dushek O, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
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- Humans, Structure-Activity Relationship, Antibodies, Monoclonal immunology, Mutation genetics, Antibodies, Neutralizing immunology, Antibody Affinity, SARS-CoV-2 immunology, SARS-CoV-2 metabolism, SARS-CoV-2 genetics, Angiotensin-Converting Enzyme 2 metabolism, Angiotensin-Converting Enzyme 2 chemistry, COVID-19 immunology, COVID-19 virology, Antibodies, Viral immunology, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus metabolism, Immune Evasion
- Abstract
BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founder member of RQ Biotechnology. D.I.S. consults for AstraZeneca. Oxford University holds intellectual property related to SARS-CoV-2 mAbs discovered in G.R.S.’s laboratory. S.J.D. is a scientific advisor to the Scottish Parliament on COVID-19., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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32. Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays.
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Mühlemann B, Wilks SH, Baracco L, Bekliz M, Carreño JM, Corman VM, Davis-Gardner ME, Dejnirattisai W, Diamond MS, Douek DC, Drosten C, Eckerle I, Edara VV, Ellis M, Fouchier RAM, Frieman M, Godbole S, Haagmans B, Halfmann PJ, Henry AR, Jones TC, Katzelnick LC, Kawaoka Y, Kimpel J, Krammer F, Lai L, Liu C, Lusvarghi S, Meyer B, Mongkolsapaya J, Montefiori DC, Mykytyn A, Netzl A, Pollett S, Rössler A, Screaton GR, Shen X, Sigal A, Simon V, Subramanian R, Supasa P, Suthar MS, Türeli S, Wang W, Weiss CD, and Smith DJ
- Subjects
- Animals, Humans, Mice, Cricetinae, Disease Models, Animal, SARS-CoV-2 immunology, COVID-19 immunology, COVID-19 blood, COVID-19 virology, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Neutralization Tests, Antibodies, Viral blood, Antibodies, Viral immunology
- Abstract
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models.
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- 2024
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33. Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.
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Hunt M, Hinrichs AS, Anderson D, Karim L, Dearlove BL, Knaggs J, Constantinides B, Fowler PW, Rodger G, Street T, Lumley S, Webster H, Sanderson T, Ruis C, de Maio N, Amenga-Etego LN, Amuzu DSY, Avaro M, Awandare GA, Ayivor-Djanie R, Bashton M, Batty EM, Bediako Y, De Belder D, Benedetti E, Bergthaler A, Boers SA, Campos J, Carr RAA, Cuba F, Dattero ME, Dejnirattisai W, Dilthey A, Duedu KO, Endler L, Engelmann I, Francisco NM, Fuchs J, Gnimpieba EZ, Groc S, Gyamfi J, Heemskerk D, Houwaart T, Hsiao NY, Huska M, Hölzer M, Iranzadeh A, Jarva H, Jeewandara C, Jolly B, Joseph R, Kant R, Ki KKK, Kurkela S, Lappalainen M, Lataretu M, Liu C, Malavige GN, Mashe T, Mongkolsapaya J, Montes B, Molina Mora JA, Morang'a CM, Mvula B, Nagarajan N, Nelson A, Ngoi JM, da Paixão JP, Panning M, Poklepovich T, Quashie PK, Ranasinghe D, Russo M, San JE, Sanderson ND, Scaria V, Screaton G, Sironen T, Sisay A, Smith D, Smura T, Supasa P, Suphavilai C, Swann J, Tegally H, Tegomoh B, Vapalahti O, Walker A, Wilkinson RJ, Williamson C, de Oliveira T, Peto TE, Crook D, Corbett-Detig R, and Iqbal Z
- Abstract
The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers., Competing Interests: Conflict of Interest Gavin Screaton sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founding member of RQ Biotechnology.
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- 2024
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34. Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection.
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Liu C, Das R, Dijokaite-Guraliuc A, Zhou D, Mentzer AJ, Supasa P, Selvaraj M, Duyvesteyn HME, Ritter TG, Temperton N, Klenerman P, Dunachie SJ, Paterson NG, Williams MA, Hall DR, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
- Subjects
- Humans, Mutation, SARS-CoV-2 genetics, Antibodies, Neutralizing, Antibodies, Viral, Antibodies, Monoclonal, Postoperative Complications
- Abstract
The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called 'FLip' mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86., (© 2024. The Author(s).)
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- 2024
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35. Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS) consortium.
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Nhu LNT, Chambers M, Chantratita N, Cheah PY, Day NPJ, Dejnirattisai W, Dunachie SJ, Grifoni A, Hamers RL, Hill J, Jones EY, Klenerman P, Mongkolsapaya J, Screaton G, Sette A, Stuart DI, Tan CW, Thwaites G, Thanh VD, Wang LF, and Tan LV
- Abstract
A strong and effective COVID-19 and future pandemic responses rely on global efforts to carry out surveillance of infections and emerging SARS-CoV-2 variants and to act accordingly in real time. Many countries in Southeast Asia lack capacity to determine the potential threat of new variants, or other emerging infections. Funded by Wellcome, the Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS) consortium aims to develop and apply a multidisciplinary research platform in Southeast Asia (SEA) for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby informing coordinated local, regional and global responses to the COVID-19 pandemic. Our proposal is delivered by the Vietnam and Thailand Wellcome Africa Asia Programmes, bringing together a multidisciplinary team in Indonesia, Thailand and Vietnam with partners in Singapore, the UK and the USA. Herein we outline five work packages to deliver strengthened regional scientific capacity that can be rapidly deployed for future outbreak responses., Competing Interests: Competing interests: L.V.T. received a consulting fee from MIMS Pte. Ltd. G.R.S. is in the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca and is a founder member of RQ Biotechnology. No other competing interests were disclosed., (Copyright: © 2024 Nhu LNT et al.)
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- 2024
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36. The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.
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Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
- Subjects
- Humans, SARS-CoV-2 genetics, Antibodies, Monoclonal, Epitopes, Spike Glycoprotein, Coronavirus genetics, Antibodies, Viral, Antibodies, Neutralizing, COVID-19, Syndactyly
- Abstract
Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response., (© 2024. The Author(s).)
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- 2024
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37. Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3-4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination.
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Assawakosri S, Kanokudom S, Suntronwong N, Chansaenroj J, Auphimai C, Nilyanimit P, Vichaiwattana P, Thongmee T, Duangchinda T, Chantima W, Pakchotanon P, Srimuan D, Thatsanathorn T, Klinfueng S, Sudhinaraset N, Wanlapakorn N, Mongkolsapaya J, Honsawek S, and Poovorawan Y
- Abstract
Background: Several countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine-induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming., Methods: A total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90-120 after booster., Results: A waning of total RBD immunoglobulin (Ig) levels, anti -RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90-120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50 % to 75 % among all booster vaccine., Conclusions: The antibody response substantially waned after 90-120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
- Published
- 2023
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38. Heterologous prime-boost immunization induces protection against dengue virus infection in cynomolgus macaques.
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Keelapang P, Ketloy C, Puttikhunt C, Sriburi R, Prompetchara E, Sae-Lim M, Siridechadilok B, Duangchinda T, Noisakran S, Charoensri N, Suriyaphol P, Suparattanagool P, Utaipat U, Masrinoul P, Avirutnan P, Mongkolsapaya J, Screaton G, Auewarakul P, Malaivijitnond S, Yoksan S, Malasit P, Ruxrungtham K, Pulmanausahakul R, and Sittisombut N
- Subjects
- Animals, Humans, Antibodies, Viral, Macaca fascicularis, Immunization, Secondary, Dengue, Dengue Vaccines administration & dosage, Dengue Virus, Vaccines, Virus-Like Particle administration & dosage
- Abstract
Importance: Currently licensed dengue vaccines do not induce long-term protection in children without previous exposure to dengue viruses in nature. These vaccines are based on selected attenuated strains of the four dengue serotypes and employed in combination for two or three consecutive doses. In our search for a better dengue vaccine candidate, live attenuated strains were followed by non-infectious virus-like particles or the plasmids that generate these particles upon injection into the body. This heterologous prime-boost immunization induced elevated levels of virus-specific antibodies and helped to prevent dengue virus infection in a high proportion of vaccinated macaques. In macaques that remained susceptible to dengue virus, distinct mechanisms were found to account for the immunization failures, providing a better understanding of vaccine actions. Additional studies in humans in the future may help to establish whether this combination approach represents a more effective means of preventing dengue by vaccination., Competing Interests: N.S., P.K., N.C., and M.S.-L. were listed as inventors in patents and patent applications involving the mature virus-like particles of flaviviruses. Other authors declare that they do not have conflicts of interest.
- Published
- 2023
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39. Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera.
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Mühlemann B, Wilks SH, Baracco L, Bekliz M, Carreño JM, Corman VM, Davis-Gardner ME, Dejnirattisai W, Diamond MS, Douek DC, Drosten C, Eckerle I, Edara VV, Ellis M, Fouchier RAM, Frieman M, Godbole S, Haagmans B, Halfmann PJ, Henry AR, Jones TC, Katzelnick LC, Kawaoka Y, Kimpel J, Krammer F, Lai L, Liu C, Lusvarghi S, Meyer B, Mongkolsapaya J, Montefiori DC, Mykytyn A, Netzl A, Pollett S, Rössler A, Screaton GR, Shen X, Sigal A, Simon V, Subramanian R, Supasa P, Suthar M, Türeli S, Wang W, Weiss CD, and Smith DJ
- Abstract
The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera., Competing Interests: VMC: Named on patents regarding SARS-CoV-2 serological testing and monoclonal antibodies. MSD: Consultant for Inbios, Vir Biotechnology, Ocugen, Topspin Therapeutics, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Generate Biomedicines, and Emergent BioSolutions. YK: Received unrelated funding support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., Shionogi & Co. LTD, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation, and Fuji Rebio. IE: Research grant and speakers fees from Moderna. BMe: Research grant from Moderna. GRS: Is on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. MS: Serves in an advisory role for Ocugen, Inc. SP: Reports that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the U.S. Government COVID-19 response. Neither is related to the work presented here.
- Published
- 2023
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40. Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.
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Hornsby H, Nicols AR, Longet S, Liu C, Tomic A, Angyal A, Kronsteiner B, Tyerman JK, Tipton T, Zhang P, Gallis M, Supasa P, Selvaraj M, Abraham P, Neale I, Ali M, Barratt NA, Nell JM, Gustafsson L, Strickland S, Grouneva I, Rostron T, Moore SC, Hering LM, Dobson SL, Bibi S, Mongkolsapaya J, Lambe T, Wootton D, Hall V, Hopkins S, Dong T, Barnes E, Screaton G, Richter A, Turtle L, Rowland-Jones SL, Carroll M, Duncan CJA, Klenerman P, Dunachie SJ, Payne RP, and de Silva TI
- Subjects
- Humans, Immunity, Antibodies, Viral immunology, Antibodies, Neutralizing, Immunoglobulin A, T-Lymphocytes immunology, Immunity, Mucosal, Male, Female, Adult, COVID-19 immunology, COVID-19 virology, SARS-CoV-2 classification, COVID-19 Vaccines administration & dosage
- Abstract
Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3
rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants., (© 2023. Springer Nature Limited.)- Published
- 2023
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41. Blockade-of-Binding Activities toward Envelope-Associated, Type-Specific Epitopes as a Correlative Marker for Dengue Virus-Neutralizing Antibody.
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Keelapang P, Kraivong R, Pulmanausahakul R, Sriburi R, Prompetchara E, Kaewmaneephong J, Charoensri N, Pakchotanon P, Duangchinda T, Suparattanagool P, Luangaram P, Masrinoul P, Mongkolsapaya J, Screaton G, Ruxrungtham K, Auewarakul P, Yoksan S, Malasit P, Puttikhunt C, Ketloy C, and Sittisombut N
- Subjects
- Humans, Epitopes, Antibodies, Viral, Antibodies, Neutralizing, Cross Reactions, Dengue Virus, Dengue diagnosis, Dengue prevention & control
- Abstract
Humans infected with dengue virus (DENV) acquire long-term protection against the infecting serotype, whereas cross-protection against other serotypes is short-lived. Long-term protection induced by low levels of type-specific neutralizing antibodies can be assessed using the virus-neutralizing antibody test. However, this test is laborious and time-consuming. In this study, a blockade-of-binding enzyme-linked immunoassay was developed to assess antibody activity by using a set of neutralizing anti-E monoclonal antibodies and blood samples from dengue virus-infected or -immunized macaques. Diluted blood samples were incubated with plate-bound dengue virus particles before the addition of an enzyme-conjugated antibody specific to the epitope of interest. Based on blocking reference curves constructed using autologous purified antibodies, sample blocking activity was determined as the relative concentration of unconjugated antibody that resulted in the same percent signal reduction. In separate DENV-1-, -2-, -3-, and -4-related sets of samples, moderate to strong correlations of the blocking activity with neutralizing antibody titers were found with the four type-specific antibodies 1F4, 3H5, 8A1, and 5H2, respectively. Significant correlations were observed for single samples taken 1 month after infection as well as samples drawn before and at various time points after infection/immunization. Similar testing using a cross-reactive EDE-1 antibody revealed a moderate correlation between the blocking activity and the neutralizing antibody titer only for the DENV-2-related set. The potential usefulness of the blockade-of-binding activity as a correlative marker of neutralizing antibodies against dengue viruses needs to be validated in humans. IMPORTANCE This study describes a blockade-of-binding assay for the determination of antibodies that recognize a selected set of serotype-specific or group-reactive epitopes in the envelope of dengue virus. By employing blood samples collected from dengue virus-infected or -immunized macaques, moderate to strong correlations of the epitope-blocking activities with the virus-neutralizing antibody titers were observed with serotype-specific blocking activities for each of the four dengue serotypes. This simple, rapid, and less laborious method should be useful for the evaluation of antibody responses to dengue virus infection and may serve as, or be a component of, an in vitro correlate of protection against dengue in the future., Competing Interests: The authors declare no conflict of interest.
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- 2023
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42. Corrigendum: Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.
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Thursz M, Sadiq F, Tree JA, Karayiannis P, Beasley DWC, Dejnirattisai W, Mongkolsapaya J, Screaton G, Wand M, Elmore MJ, Carroll MW, Matthews I, and Thomas H
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- 2023
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43. Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.
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Thursz M, Sadiq F, Tree JA, Karayiannis P, Beasley DWC, Dejnirattisai W, Mongkolsapaya J, Screaton G, Wand M, Elmore MJ, Carroll MW, Matthews I, and Thomas H
- Subjects
- Humans, Mice, Animals, Rats, Antiviral Agents pharmacology, SARS-CoV-2, Interferon-alpha, Encephalomyocarditis virus, Phosphoric Diester Hydrolases, COVID-19, RNA Viruses
- Abstract
The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in vitro . Cross reactivity of PDE12 inhibitors with other PDEs and in vivo toxicity were measured. In EMCV assays, CO-17 potentiated the effect of IFNα by 3 log
10 . The compounds were selective for PDE12 when tested against a panel of other PDEs and non-toxic at up to 42 mg kg-1 in rats in vivo . Thus, we have identified PDE12 inhibitors (CO-17 and CO-63), and established the principle that inhibitors of PDE12 have antiviral properties. Early studies suggest these PDE12 inhibitors are well tolerated at the therapeutic range, and reduce viral load in studies of DENV, HCV, WNV and SARS-CoV-2 in human cells and WNV in a mouse model.- Published
- 2023
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44. Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy.
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Ragonnet-Cronin M, Nutalai R, Huo J, Dijokaite-Guraliuc A, Das R, Tuekprakhon A, Supasa P, Liu C, Selvaraj M, Groves N, Hartman H, Ellaby N, Mark Sutton J, Bahar MW, Zhou D, Fry E, Ren J, Brown C, Klenerman P, Dunachie SJ, Mongkolsapaya J, Hopkins S, Chand M, Stuart DI, Screaton GR, and Rokadiya S
- Subjects
- Humans, Antibodies, Monoclonal therapeutic use, Immunotherapy, Mutation, Antibodies, Neutralizing, Antibodies, Viral, SARS-CoV-2 genetics, COVID-19
- Abstract
COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum., (© 2023. The Author(s).)
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- 2023
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45. Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination.
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Yin Z, Chen JL, Lu Y, Wang B, Godfrey L, Mentzer AJ, Yao X, Liu G, Wellington D, Zhao Y, Wing PAC, Dejnirattisa W, Supasa P, Liu C, Hublitz P, Beveridge R, Waugh C, Clark SA, Clark K, Sopp P, Rostron T, Mongkolsapaya J, Screaton GR, Ogg G, Ewer K, Pollard AJ, Gilbert S, Knight JC, Lambe T, Smith GL, Dong T, and Peng Y
- Subjects
- Humans, ChAdOx1 nCoV-19, Vaccination, Antibodies, Viral, SARS-CoV-2, COVID-19
- Abstract
Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations., Competing Interests: Declaration of interests A.J.P. is chair of the DHSC Joint Committee on Vaccination and Immunisation (JCVI) but does not take part in the JCVI COVID-19 committee. Oxford University has entered into a partnership with AstraZeneca for development of a COVID-19 vaccine. A.J.P. has provided advice to Shionogi & Co., Ltd., on the development of a COVID-19 vaccine., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)
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- 2023
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46. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.
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Dijokaite-Guraliuc A, Das R, Zhou D, Ginn HM, Liu C, Duyvesteyn HME, Huo J, Nutalai R, Supasa P, Selvaraj M, de Silva TI, Plowright M, Newman TAH, Hornsby H, Mentzer AJ, Skelly D, Ritter TG, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Roemer C, Peacock TP, Paterson NG, Williams MA, Hall DR, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
- Subjects
- Humans, SARS-CoV-2, Amino Acid Substitution, Antibodies, Monoclonal, Antibodies, Viral, Antibodies, Neutralizing, Antibody Formation, COVID-19
- 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (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 titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board, consults for AstraZeneca, and is a founding member of RQ Biotechnology. D.I.S. consults for AstraZeneca. Oxford University holds intellectual property related to SARS-CoV-2 mAbs discovered in G.R.S.’s laboratory. S.J.D. is a scientific advisor to the Scottish Parliament on COVID-19., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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47. Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens.
- Author
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Moore SC, Kronsteiner B, Longet S, Adele S, Deeks AS, Liu C, Dejnirattisai W, Reyes LS, Meardon N, Faustini S, Al-Taei S, Tipton T, Hering LM, Angyal A, Brown R, Nicols AR, Dobson SL, Supasa P, Tuekprakhon A, Cross A, Tyerman JK, Hornsby H, Grouneva I, Plowright M, Zhang P, Newman TAH, Nell JM, Abraham P, Ali M, Malone T, Neale I, Phillips E, Wilson JD, Murray SM, Zewdie M, Shields A, Horner EC, Booth LH, Stafford L, Bibi S, Wootton DG, Mentzer AJ, Conlon CP, Jeffery K, Matthews PC, Pollard AJ, Brown A, Rowland-Jones SL, Mongkolsapaya J, Payne RP, Dold C, Lambe T, Thaventhiran JED, Screaton G, Barnes E, Hopkins S, Hall V, Duncan CJA, Richter A, Carroll M, de Silva TI, Klenerman P, Dunachie S, and Turtle L
- Subjects
- Humans, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19, Prospective Studies, SARS-CoV-2, Antibodies, Neutralizing, Health Personnel, Immunity, Humoral, COVID-19, Vaccines
- Abstract
Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination., Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination., Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose., Conclusions: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease., Funding: Department for Health and Social Care, Medical Research Council., Competing Interests: Declaration of interests S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19, for which she receives a fee. A.J.P. is Chair of UK Department of Health and Social Care’s (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) but does not participate in policy decisions on COVID-19 vaccines. He was previously a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. A.J.P. is chief investigator on clinical trials of Oxford University’s COVID-19 vaccine funded by NIHR. Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca. G.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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48. Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.
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Emmenegger M, De Cecco E, Lamparter D, Jacquat RPB, Riou J, Menges D, Ballouz T, Ebner D, Schneider MM, Morales IC, Doğançay B, Guo J, Wiedmer A, Domange J, Imeri M, Moos R, Zografou C, Batkitar L, Madrigal L, Schneider D, Trevisan C, Gonzalez-Guerra A, Carrella A, Dubach IL, Xu CK, Meisl G, Kosmoliaptsis V, Malinauskas T, Burgess-Brown N, Owens R, Hatch S, Mongkolsapaya J, Screaton GR, Schubert K, Huck JD, Liu F, Pojer F, Lau K, Hacker D, Probst-Müller E, Cervia C, Nilsson J, Boyman O, Saleh L, Spanaus K, von Eckardstein A, Schaer DJ, Ban N, Tsai CJ, Marino J, Schertler GFX, Ebert N, Thiel V, Gottschalk J, Frey BM, Reimann RR, Hornemann S, Ring AM, Knowles TPJ, Puhan MA, Althaus CL, Xenarios I, Stuart DI, and Aguzzi A
- Abstract
Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae., Competing Interests: TPJK is a member of the board of directors of Fluidic Analytics. AA is a member of the board of directors of Mabylon AG which has funded antibody-related work in the Aguzzi lab in the past. All other authors declare no competing interests., (© 2023 The Authors.)
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- 2023
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49. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75.
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Huo J, Dijokaite-Guraliuc A, Liu C, Zhou D, Ginn HM, Das R, Supasa P, Selvaraj M, Nutalai R, Tuekprakhon A, Duyvesteyn HME, Mentzer AJ, Skelly D, Ritter TG, Amini A, Bibi S, Adele S, Johnson SA, Paterson NG, Williams MA, Hall DR, Plowright M, Newman TAH, Hornsby H, de Silva TI, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Pollard AJ, Lambe T, Goulder P, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
- Subjects
- Humans, Angiotensin-Converting Enzyme 2, SARS-CoV-2, Antibodies, COVID-19, Hepatitis D
- Abstract
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared with BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection, which may explain the rapid spread in India, where where there is a high background of Delta infection. ACE2 affinity appears to be prioritized over greater escape., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board, consults for Astra Zeneca, and is a founding member of RQ Biotechnology. Oxford University holds intellectual property related to the Oxford-Astra Zeneca vaccine and SARS-CoV-2 mAbs discovered in G.R.S.’s laboratory. A.J.P. is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee and is a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project whilst the study was conducted. S.J.D. is a scientific advisor to the Scottish Parliament on COVID-19., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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50. Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination.
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Suntronwong N, Kanokudom S, Auphimai C, Assawakosri S, Thongmee T, Vichaiwattana P, Duangchinda T, Chantima W, Pakchotanon P, Chansaenroj J, Puenpa J, Nilyanimit P, Srimuan D, Thatsanatorn T, Sudhinaraset N, Wanlapakorn N, Mongkolsapaya J, and Poovorawan Y
- Subjects
- Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, COVID-19 Vaccines, ChAdOx1 nCoV-19, Humans, Immunity, Interferon-gamma, RNA, Messenger genetics, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus genetics, Vaccination, COVID-19 prevention & control, Vaccines
- Abstract
The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination, because it harbors mutations. Here we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses. A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4-5 months were enrolled, to receive AZD1222, BNT162b2, or mRNA-1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of severe acute respiratory syndrome coronavirus 2-binding antibodies were measured using enzyme-linked immunosorbent assay. The NAb titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon-γ responses were measured to observe the T-cell activation. A substantial loss in neutralizing potency to omicron variant was found at 4-5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. In addition, individuals boosted with messenger RNA (mRNA) vaccines develop a T-cell response to spike protein, whereas those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events. Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T-cell response., (© 2022 Wiley Periodicals LLC.)
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- 2022
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