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1. Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

Author

Sebastian Emmanuel Willyanto, Yohanes Audric Alimsjah, Krisanto Tanjaya, Aekkachai Tuekprakhon, and Aulia Rahmi Pawestri

Subjects
CAR T-cell therapy, immunotherapy, acute lymphoblastic leukaemia, targeted therapy, oncoimmunology, Medicine
Abstract

AbstractBackground Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.Methods The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).Results Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.Conclusion Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.

Published
2024
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2. Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Author

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

Subjects
Science
Abstract

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.

Published
2023
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3. Genotypic and phenotypic profiles of EYS gene-related retinitis pigmentosa: a retrospective study

Author

Ragkit Suvannaboon, Aulia Rahmi Pawestri, Worapoj Jinda, Aekkachai Tuekprakhon, Adisak Trinavarat, and La-ongsri Atchaneeyasakul

Subjects
Medicine, Science
Abstract

Abstract Retinitis pigmentosa (RP) affects 1:5000 individuals worldwide. Interestingly, variations in 271 RP-related genes are indicated to vary among populations. We aimed to evaluate the genetic prevalence and phenotypic profiles of Thai patients with RP. The clinical and whole exome sequencing data of 125 patients suggestive of inherited retinal diseases (IRD), particularly non-syndromic RP, were assessed. We found a total of 258 variants (63% of which remained unavailable in the ClinVar database) in 91 IRD-associated genes. Among the detected genes, the eyes shut homolog (EYS) gene showed the highest prevalence. We also provide insights into the genotypic, baseline, and follow-up clinical presentations of seven patients with disease-causing EYS variations. This study could provide comprehension of the prevalence of RP-related genes involved in the Asian population. It might also provide information to establish advanced and personalised therapy for RP in the Thai population.

Published
2022
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4. 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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5. A cell-based, SARS-CoV-2 spike protein interaction assay to inform the neutralising capacity of recombinant and patient sera antibodies

Author

Neale Harrison, Lauren Richardson, Chiara Pallini, Ines Morano, Elizabeth Jinks, Jamie Cowley, Hujo Chan, Harriet J. Hill, Aekkachai Tuekprakhon, Zhi Li, Cristina Matas de las Heras, Ana Teodosio, Andrea S. Lavado, Robert Moring, Ayesha Ashraf, Timothy R. Dafforn, Dimitris K. Grammatopoulos, John Gordon, Catherine A. Brady, Lawrence S. Young, Nicholas M. Barnes, Zania Stamataki, and Omar S. Qureshi

Subjects
SARS-CoV-2, ACE2, spike protein, antibody discovery, virology, variant, Microbiology, QR1-502
Abstract

IntroductionThe engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells, and, therefore, blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine elicited serum antibodies. The emergence of SARS-CoV-2 variants has necessitated the development of adaptable assays that can be applied to assess the effectiveness of antibody-based therapeutics.MethodsThrough the testing of a range of recombinant spike proteins, we have developed a cell-based, ACE2/spike protein interaction assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell-bound spike protein fluorescence.ResultsUsing spike proteins from the original “Wuhan” SARS-CoV-2 strain and the Delta and Omicron variants, we identified differential blocking activity of three monoclonal antibodies directed against the spike receptor-binding domain. Importantly, biological activity in the spike interaction assay translated to efficacy in a SARS-CoV-2 infection assay.DiscussionThe spike protein interaction assay can be used to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable for quantification of the impact of antibodies against new and emerging SARS-CoV-2 variants.

Published
2023
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8. Autoantibody profiles and clinical association in Thai patients with autoimmune retinopathy

Author

Aulia Rahmi Pawestri, Niracha Arjkongharn, Ragkit Suvannaboon, Aekkachai Tuekprakhon, Vichien Srimuninnimit, Suthipol Udompunthurak, La-ongsri Atchaneeyasakul, Ajchara Koolvisoot, and Adisak Trinavarat

Subjects
Medicine, Science
Abstract

Abstract Autoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to be involved in the pathogenesis. This retrospective cohort study assessed the antiretinal autoantibody profiles and their association with clinical outcomes of AIR patients in Thailand. We included 44 patients, 75% were females, with the overall median age of onset of 48 (17–74, IQR 40–55.5) years. Common clinical presentations were nyctalopia (65.9%), blurred vision (52.3%), constricted visual field (43.2%), and nonrecordable electroretinography (65.9%). Underlying malignancy and autoimmune diseases were found in 2 and 12 female patients, respectively. We found 41 autoantibodies, with anti-α-enolase (65.9%) showing the highest prevalence, followed by anti-CAII (43.2%), anti-aldolase (40.9%), and anti-GAPDH (36.4%). Anti-aldolase was associated with male gender (P = 0.012, OR 7.11, 95% CI 1.54–32.91). Anti-CAII showed significant association with age of onset (P = 0.025, 95% CI − 17.28 to − 1.24), while anti-α-enolase (P = 0.002, OR 4.37, 95% CI 1.83–10.37) and anti-GAPDH (P = 0.001, OR 1.87, 95% CI 1.32–2.64) were significantly associated with nonrecordable electroretinography. Association between the antibody profiles and clinical outcomes may be used to direct and adjust the treatment plans and provide insights in the pathogenesis of AIR.

Published
2021
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9. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa

Author

Aekkachai Tuekprakhon, Siripakorn Sangkitporn, Adisak Trinavarat, Aulia Rahmi Pawestri, Visit Vamvanij, Monchai Ruangchainikom, Panya Luksanapruksa, Phitchapa Pongpaksupasin, Areerat Khorchai, Acharaporn Dambua, Patcharaporn Boonchu, Chonlada Yodtup, Mongkol Uiprasertkul, Somchai Sangkitporn, and La-ongsri Atchaneeyasakul

Subjects
Retinitis pigmentosa (RP), Inherited retinal diseases, Mesenchymal stem cell, Stem cell therapy, Phase I clinical trial, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract

Abstract Background Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. Methods This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. Results During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. Conclusion Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. Trial registration ClinicalTrials.gov, NCT01531348 . Registered on February 10, 2012

Published
2021
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11. Promising application of monoclonal antibody against chikungunya virus E1-antigen across genotypes in immunochromatographic rapid diagnostic tests

Author

Keita Suzuki, Ralph Huits, Juthamas Phadungsombat, Aekkachai Tuekprakhon, Emi E. Nakayama, Riemsdijk van den Berg, Barbara Barbé, Lieselotte Cnops, Rummana Rahim, Abu Hasan, Hisahiko Iwamoto, Pornsawan Leaungwutiwong, Marjan van Esbroeck, Mizanur Rahman, and Tatsuo Shioda

Subjects
Chikungunya virus, E1 protein, Rapid immunochromatographic RDT, Monoclonal antibody, ECSA, Asian genotype, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Central/South African (ECSA), West African (WA), and Asian. Previously, a rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity for certain ECSA-genotype viruses, but this test showed poor performance against the Asian-genotype virus that is spreading in the American continents. We found that the reactivity of one monoclonal antibody (MAb) used in the IC rapid diagnostic test (RDT) is affected by a single amino acid substitution in E1. Therefore, we developed new MAbs that exhibited specific recognition of all three genotypes of CHIKV. Methods Using a combination of the newly generated MAbs, we developed a novel version of the IC RDT with improved sensitivity to Asian-genotype CHIKV. To evaluate the sensitivity, specificity, and cross-reactivity of the new version of the IC RDT, we first used CHIKV isolates and E1-pseudotyped lentiviral vectors. We then used clinical specimens obtained in Aruba in 2015 and in Bangladesh in 2017 for further evaluation of RDT sensitivity and specificity. Another alphavirus, sindbis virus (SINV), was used to test RDT cross-reactivity. Results The new version of the RDT detected Asian-genotype CHIKV at titers as low as 10^4 plaque-forming units per mL, a concentration that was below the limit of detection of the old version. The new RDT had sensitivity to the ECSA genotype that was comparable with that of the old version, yielding 92% (92 out of 100) sensitivity (95% confidence interval 85.0–95.9) and 100% (100 out of 100) specificity against a panel of 100 CHIKV-positive and 100 CHIKV-negative patient sera obtained in the 2017 outbreak in Bangladesh. Conclusions Our newly developed CHIKV antigen-detecting RDT demonstrated high levels of sensitivity and lacked cross-reactivity against SINV. These results suggested that our new version of the CHIKV E1-antigen RDT is promising for use in areas in which the Asian and ECSA genotypes of CHIKV circulate. Further validation with large numbers of CHIKV-positive and -negative clinical samples is warranted. (323 words).

Published
2020
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13. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa

Author

Tuekprakhon, Aekkachai, Sangkitporn, Siripakorn, Trinavarat, Adisak, Pawestri, Aulia Rahmi, Vamvanij, Visit, Ruangchainikom, Monchai, Luksanapruksa, Panya, Pongpaksupasin, Phitchapa, Khorchai, Areerat, Dambua, Acharaporn, Boonchu, Patcharaporn, Yodtup, Chonlada, Uiprasertkul, Mongkol, Sangkitporn, Somchai, and Atchaneeyasakul, La-ongsri

Published
2021
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14. Rare Co-Occurrence of Visual Snow in a Female Carrier With RPGRORF15-Associated Retinal Disorder

Author

Aekkachai Tuekprakhon, Aulia Rahmi Pawestri, Ragkit Suvannaboon, Ketwarin Thongyou, Adisak Trinavarat, and La-Ongsri Atchaneeyasakul

Subjects
x-linked retinitis pigmentosa, visual snow, retinitis pigmentosa GTPase regulator gene, random X-chromosome inactivation, case report, inherited retinal disease, Genetics, QH426-470
Abstract

X-linked retinitis pigmentosa (XLRP), a rare form of retinitis pigmentosa (RP), is predominantly caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. Affected males often present with severe phenotypes and early disease onset. In contrast, female carriers are usually asymptomatic or show stationary phenotypes. Herein, we reported an 8-year-old female carrier, a daughter of a confirmed RP father with RPGR mutation, with an early onset of progressive cone-rod pattern retinal dystrophy. Additionally, the carrier experienced visual snow-like symptom as long as she recalled. Ophthalmological examination showed the reduction of visual acuity and attenuation of photoreceptor functions since the age of 5 years. Further analysis revealed a heterozygous pathogenic variant of the RPGR gene and a random X-inactivation pattern. Although she harboured an identical RPGR variant as the father, there were phenotypic intrafamilial variations. The information on the variety of genotypic and phenotypic presentations in XLRP carriers is essential for further diagnosis, management, and monitoring of these cases, including the design of future gene therapy trials.

Published
2021
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15. Porous Cellulose Thin Films as Sustainable and Effective Antimicrobial Surface Coatings

Author

Shaojun Qi, Ioannis Kiratzis, Pavan Adoni, Aekkachai Tuekprakhon, Harriet James Hill, Zania Stamataki, Aneesa Nabi, David Waugh, Javier Rodriguez Rodriguez, Stuart Matthew Clarke, Peter J. Fryer, Zhenyu J. Zhang, Clarke, Stuart Matthew [0000-0001-5224-2368], Fryer, Peter J [0000-0003-4767-7839], Zhang, Zhenyu J [0000-0003-0243-2109], and Apollo - University of Cambridge Repository

Subjects
Anti-Infective Agents, SARS-CoV-2, Surface Properties, antimicrobial, Humans, COVID-19, Water, General Materials Science, robustness, film, Cellulose, Porosity, evaporation
Abstract

In the present work, we developed an effective antimicrobial surface film based on sustainable microfibrillated cellulose. The resulting porous cellulose thin film is barely noticeable to human eyes due to its submicrometer thickness, of which the surface coverage, porosity, and microstructure can be modulated by the formulations and the coating process. Using goniometers and a quartz crystal microbalance, we observed a threefold reduction in water contact angles and accelerated water evaporation kinetics on the cellulose film (more than 50% faster than that on a flat glass surface). The porous cellulose film exhibits a rapid inactivation effect against SARS-CoV-2 in 5 min, following deposition of virus-loaded droplets, and an exceptional ability to reduce contact transfer of liquid, e.g., respiratory droplets, to surfaces such as an artificial skin by 90% less than that from a planar glass substrate. It also shows excellent antimicrobial performance in inhibiting the growth of both Gram-negative and Gram-positive bacteria (Escherichia coli and Staphylococcus epidermidis) due to the intrinsic porosity and hydrophilicity. Additionally, the cellulose film shows nearly 100% resistance to scraping in dry conditions due to its strong affinity to the supporting substrate but with good removability once wetted with water, suggesting its practical suitability for daily use. Importantly, the coating can be formed on solid substrates readily by spraying, which requires solely a simple formulation of a plant-based cellulose material with no chemical additives, rendering it a scalable, affordable, and green solution as antimicrobial surface coating. Implementing such cellulose films could thus play a significant role in controlling future pan- and epidemics, particularly during the initial phase when suitable medical intervention needs to be developed and deployed.

Published
2023

16. A cell-based, SARS-CoV-2 spike protein interaction assay to inform the neutralising capacity of recombinant and patient sera antibodies

Author

Harrison, Neale, primary, Richardson, Lauren, additional, Pallini, Chiara, additional, Morano, Ines, additional, Jinks, Elizabeth, additional, Cowley, Jamie, additional, Chan, Hujo, additional, Hill, Harriet J., additional, Tuekprakhon, Aekkachai, additional, Li, Zhi, additional, Matas de las Heras, Cristina, additional, Teodosio, Ana, additional, Lavado, Andrea S., additional, Moring, Robert, additional, Ashraf, Ayesha, additional, Dafforn, Timothy R., additional, Grammatopoulos, Dimitris K., additional, Gordon, John, additional, Brady, Catherine A., additional, Young, Lawrence S., additional, Barnes, Nicholas M., additional, Stamataki, Zania, additional, and Qureshi, Omar S., additional

Published
2023
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17. 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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19. Porous Cellulose Thin Films as Sustainable and Effective Antimicrobial Surface Coatings

Author

Qi, Shaojun, primary, Kiratzis, Ioannis, additional, Adoni, Pavan, additional, Tuekprakhon, Aekkachai, additional, Hill, Harriet James, additional, Stamataki, Zania, additional, Nabi, Aneesa, additional, Waugh, David, additional, Rodriguez, Javier Rodriguez, additional, Clarke, Stuart Matthew, additional, Fryer, Peter J., additional, and Zhang, Zhenyu J., additional

Published
2023
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20. Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Author

Moore, Shona C., primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra S., additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Reyes, Laura Silva, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Dobson, Susan L., additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K., additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas A.H., additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Zewdie, Martha, additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Daniel G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James E.D., additional, Screaton, Gavin, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Duncan, Christopher J.A., additional, Richter, Alex, additional, Carroll, Miles, additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, and Turtle, Lance, additional

Published
2023
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21. Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Author

Moore, Shona C, Kronsteiner, Barbara, Longet, Stephanie, Adele, Sandra, Deeks, Alexandra S, Liu, Chang, Dejnirattisai, Wanwisa, Reyes, Laura Silva, Meardon, Naomi, Faustini, Sian, Al-Taei, Saly, Tipton, Tom, Hering, Luisa M, Angyal, Adrienn, Brown, Rebecca, Nicols, Alexander R, Dobson, Susan L, Supasa, Piyada, Tuekprakhon, Aekkachai, Cross, Andrew, Tyerman, Jessica K, Hornsby, Hailey, Grouneva, Irina, Plowright, Megan, Zhang, Peijun, Newman, Thomas AH, Nell, Jeremy M, Abraham, Priyanka, Ali, Mohammad, Malone, Tom, Neale, Isabel, Phillips, Eloise, Wilson, Joseph D, Murray, Sam M, Zewdie, Martha, Shields, Adrian, Horner, Emily C, Booth, Lucy H, Stafford, Lizzie, Bibi, Sagida, Wootton, Daniel G, Mentzer, Alexander J, Conlon, Christopher P, Jeffery, Katie, Matthews, Philippa C, Pollard, Andrew J, Brown, Anthony, Rowland-Jones, Sarah L, Mongkolsapaya, Juthathip, Payne, Rebecca P, Dold, Christina, Lambe, Teresa, Thaventhiran, James ED, Screaton, Gavin, Barnes, Eleanor, Hopkins, Susan, Hall, Victoria, Duncan, Christopher JA, Richter, Alex, Carroll, Miles, De Silva, Thushan I, Klenerman, Paul, Dunachie, Susanna, Turtle, Lance, PITCH Consortium, Nicols, Alexander R [0000-0002-1813-3819], Matthews, Philippa C [0000-0002-4036-4269], Barnes, Eleanor [0000-0002-0860-0831], Dunachie, Susanna [0000-0001-5665-6293], and Apollo - University of Cambridge Repository

Subjects
Vaccines, COVID-19 Vaccines, SARS-CoV-2, Translation to population health, Health Personnel, T cells, COVID-19, COVID vaccine, immunity, Antibodies, Neutralizing, Immunity, Humoral, antibody, ChAdOx1 nCoV-19, Humans, Prospective Studies, BNT162 Vaccine
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.

Published
2023

22. Broad-spectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development.

Author

Aekkachai Tuekprakhon, Orapim Puiprom, Tadahiro Sasaki, Johan Michiels, Koen Bartholomeeusen, Emi E Nakayama, Michael K Meno, Juthamas Phadungsombat, Ralph Huits, Kevin K Ariën, Natthanej Luplertlop, Tatsuo Shioda, and Pornsawan Leaungwutiwong

Subjects
Medicine, Science
Abstract

In response to the aggressive global spread of the mosquito-borne chikungunya virus (CHIKV), an accurate and accessible diagnostic tool is of high importance. CHIKV, an arthritogenic alphavirus, comprises three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. A previous rapid immunochromatographic (IC) test detecting CHIKV E1 protein showed promising performance for detection of the ECSA genotype. Unfortunately, this kit exhibited lower capacity for detection of the Asian genotype, currently in circulation in the Americas, reflecting the low avidity of one of the monoclonal antibodies (mAbs) in this IC kit for the E1 protein of the Asian-genotype because of a variant amino acid sequence. To address this shortcoming, we set out to generate a new panel of broad-spectrum mouse anti-CHIKV mAbs using hybridoma technology. We report here the successful generation of mouse anti-CHIKV mAbs targeting CHIKV E1 and capsid proteins. These mAbs possessed broad reactivity to all three CHIKV genotypes, while most of the mAbs lacked cross-reactivity towards Sindbis, dengue, and Zika viruses. Two of the mAbs also lacked cross-reactivity towards other alphaviruses, including O'nyong-nyong, Ross River, Mayaro, Western Equine Encephalitis, Eastern Equine Encephalitis, and Venezuelan Equine Encephalitis viruses. In addition, another two mAbs cross-reacted weakly only with most closely related O'nyong-nyong virus. Effective diagnosis is one of the keys to disease control but to date, no antibody-based rapid IC platform for CHIKV is commercially available. Thus, the application of the mAbs characterized here in the rapid diagnostic IC kit for CHIKV detection is expected to be of great value for clinical diagnosis and surveillance purposes.

Published
2018
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23. Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

Author

Shona C. Moore, Barbara Kronsteiner, Stephanie Longet, Sandra Adele, Alexandra S. Deeks, Chang Liu, Wanwisa Dejnirattisai, Laura Silva Reyes, Naomi Meardon, Sian Faustini, Saly Al-Taei, Tom Tipton, Luisa M Hering, Adrienn Angyal, Rebecca Brown, Alexander R Nicols, Susan L Dobson, Piyada Supasa, Aekkachai Tuekprakhon, Andrew Cross, Jessica K Tyerman, Hailey Hornsby, Irina Grouneva, Megan Plowright, Peijun Zhang, Thomas A.H. Newman, Jeremy M. Nell, Priyanka Abraham, Mohammad Ali, Tom Malone, Isabel Neale, Eloise Phillips, Joseph D. Wilson, Sam M. Murray, Martha Zewdie, Adrian Shields, Emily C. Horner, Lucy H. Booth, Lizzie Stafford, Sagida Bibi, Daniel G. Wootton, Alexander J. Mentzer, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Rebecca P. Payne, Christina Dold, Teresa Lambe, James E.D. Thaventhiran, Gavin Screaton, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christopher JA Duncan, Alex Richter, Miles Carroll, Thushan I. de Silva, Paul Klenerman, Susanna Dunachie, and Lance Turtle

Abstract

Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS-CoV-2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (Protective immunity from T cells in Healthcare workers (PITCH), within the larger SARS-CoV-2 immunity & reinfection evaluation (SIREN) study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. 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. We make three observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and memory B cell responses were maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels, broadened neutralising activity against variants of concern including omicron BA.1, BA.2 and BA.5, and boosted T cell responses above the 6 month level post dose 2. Thirdly, prior infection maintained its impact driving larger as well as broader T cell responses compared with never-infected people – a feature maintained until 6 months after the third dose. In conclusion, 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.

Published
2022

24. Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2

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, Sutton, J. Mark, 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
2022
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25. 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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26. Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

Author

Moore, Shona C., primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra S., additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Reyes, Laura Silva, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M, additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R, additional, Dobson, Susan L, additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K, additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas A.H., additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Zewdie, Martha, additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Daniel G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James E.D., additional, Screaton, Gavin, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Duncan, Christopher JA, additional, Richter, Alex, additional, Carroll, Miles, additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, and Turtle, Lance, additional

Published
2022
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27. 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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28. Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author

Susanna Dunachie, Gavin Screaton, David Stuart, Donal Skelly, Nigel Temperton, Eleanor Barnes, and Aekkachai Tuekprakhon

Abstract

SummaryThe 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

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

Author

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

Subjects
QR355, South Africa, Neutralization Tests, SARS-CoV-2, COVID-19, Humans, Viral Vaccines, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology
Abstract

The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. 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 sublineages, 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, they contain further mutations in the receptor-binding domain of their spikes. 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 the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the 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

30. 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

31. 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

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

Author

Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiří Zahradník, Piyada Supasa, Chang Liu, Helen M.E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J.M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra S. Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, J Kenneth Baillie, Peter JM. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christoper A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Shona C. Moore, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L. Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, AA Roger Thompson, Emma C. Thomson, Ryan S. Thwaites, Lance CW. Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Lisa Norman, Riinu Pius, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Sarah McCafferty, Richard Clark, Angie Fawkes, Kirstie Morrice, Alan Maclean, Nicola Wrobel, Lorna Donnelly, Audrey Coutts, Katarzyna Hafezi, Louise MacGillivray, Tammy Gilchrist, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O’Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, UK Research and Innovation, UKRI MRC COVID-19 Rapid Response Call, University of Oxford, Northwestern Polytechnical University (NPU), Charles University [Prague] (CU), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, University of Dayton, Universiteit Gent = Ghent University (UGENT), Computational & Applied Vegetation Ecology (CAVElab), Nanjing University of Science and Technology (NJUST), Weizmann Institute of Science [Rehovot, Israël], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, and Apollo - University of Cambridge Repository

Subjects
variants, receptor interaction, Omicron, SARS-CoV-2, [SDV]Life Sciences [q-bio], OPTIC Consortium, Spike, vaccines, 06 Biological Sciences, Article, General Biochemistry, Genetics and Molecular Biology, RBD, ISARIC4C Consortium, 11 Medical and Health Sciences, immune evasion, Developmental Biology
Abstract

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 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., A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.

Published
2022

34. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75

Author

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

Subjects
General Biochemistry, Genetics and Molecular Biology
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.

Published
2023

35. 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

36. 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
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37. The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Author

Liu, Chang, primary, Zhou, Daming, additional, Nutalai, Rungtiwa, additional, Duyvesteyn, Helen M.E., additional, Tuekprakhon, Aekkachai, additional, Ginn, Helen M., additional, Dejnirattisai, Wanwisa, additional, Supasa, Piyada, additional, Mentzer, Alexander J., additional, Wang, Beibei, additional, Case, James Brett, additional, Zhao, Yuguang, additional, Skelly, Donal T., additional, Chen, Rita E., additional, Johnson, Sile Ann, additional, Ritter, Thomas G., additional, Mason, Chris, additional, Malik, Tariq, additional, Temperton, Nigel, additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Clare, Daniel K., additional, Howe, Andrew, additional, Goulder, Philip J.R., additional, Fry, Elizabeth E., additional, Diamond, Michael S., additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Stuart, David I., additional, and Screaton, Gavin R., additional

Published
2022
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38. Evolution of Long-Term Hybrid Immunity in Healthcare Workers after Different Covid-19 Vaccination Regimens: A Longitudinal Observational Cohort Study

Author

Moore, Shona, primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra, additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Silva Reyes, Laura, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Dobson, Sue L., additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K., additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas, additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Dan G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolspaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James, additional, Screaton, Gavin R., additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria Jane, additional, Duncan, Christopher JA, additional, Richter, Alex G., additional, Carroll, Miles W., additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Turtle, Lance, additional, and Consortium, PITCH, additional

Published
2022
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39. The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Author

Thomas G Ritter, Juthathip Mongkolsapaya, Beibei Wang, Alexander J. Mentzer, Daniel K. Clare, Neil G. Paterson, Donal T. Skelly, Elizabeth E. Fry, Andy G. Howe, Nigel Temperton, Jingshan Ren, Piyada Supasa, Helen M. Ginn, Helen M. E. Duyvesteyn, S A Johnson, David I. Stuart, Tariq Malik, Wanwisa Dejnirattisai, Aekkachai Tuekprakhon, D. Zhou, Michael S. Diamond, Gavin R. Screaton, David R. Hall, Philip J. R. Goulder, Rita E. Chen, R Nutalai, Chris Jb Mason, Mark A. Williams, James Brett Case, Yuguang Zhao, and Chang Liu

Subjects
Male, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Mice, Transgenic, Biology, Antibodies, Viral, Microbiology, Article, Antigenic distance, Mice, Antigen, Neutralization Tests, Immunity, Virology, Chlorocebus aethiops, Animals, Humans, Beta (finance), Vero Cells, Cells, Cultured, QR355, SARS-CoV-2, Antibodies, Monoclonal, COVID-19, Spike Protein, Antibodies, Neutralizing, Neutralizing epitope, HEK293 Cells, Antibody response, Antibody Formation, Spike Glycoprotein, Coronavirus, Female, Parasitology, Protein Binding
Abstract

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1 and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor binding domain (RBD). Two of these RBD-binding mAbs recognise a neutralizing epitope conserved between SARS-CoV-1 and -2, whilst 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses., Graphical Abstract, Liu et al. generated 674 antibodies from patients infected with the SARS-CoV-2 Beta variant. 18 out of 27 most potent neutralizing antibodies isolated target the 3 mutations present in the receptor binding domain of this variant. This underscores the poor neutralization by Beta serum of early pandemic and Delta viruses.

Published
2021

40. Antibody evasion by the P.1 strain of SARS-CoV-2

Author

Beibei Wang, D. Zhou, Elizabeth E. Fry, Julian C. Knight, Amy Flaxman, Valdinete Alves do Nascimento, Alexander J. Mentzer, E Barnes, Alex Pauvolid-Corrêa, Sarah C. Gilbert, M Bittaye, Mark A. Williams, Hulswit Rjg., Gavin R. Screaton, Sandra Belij-Rammerstorfer, Chang Liu, Andrew J. Pollard, David R. Hall, Tao Dong, David I. Stuart, Christina Dold, Felipe Gomes Naveca, Wanwisa Dejnirattisai, Elizabeth A. Clutterbuck, Paul Klenerman, Neil G. Paterson, Helen M. Ginn, C Fernandes da Costa, R Levin, Jingshan Ren, Duyvesteyn Hme., Thomas S. Walter, Aekkachai Tuekprakhon, Miles W. Carroll, Donal T. Skelly, R Nutalai, Yuguang Zhao, Thomas A. Bowden, D W Crook, S A Costa Clemens, Marilda M. Siqueira, P Supasa, Susanna Dunachie, S Bibi, Teresa Lambe, Paola Cristina Resende, Cesar Lopez-Camacho, J Slon-Campos, Juthathip Mongkolsapaya, and Fabrícia F. Nascimento

Subjects
medicine.drug_class, medicine.disease_cause, Monoclonal antibody, Immunoglobulin light chain, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Virus, Neutralization, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, medicine, Humans, Binding site, Neutralizing antibody, COVID-19 Serotherapy, 030304 developmental biology, Immune Evasion, Sequence Deletion, 0303 health sciences, Mutation, Vaccines, Binding Sites, biology, SARS-CoV-2, Vaccination, Immunization, Passive, Antibodies, Monoclonal, COVID-19, Virology, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus, biology.protein, Antibody, 030217 neurology & neurosurgery, Protein Binding
Abstract

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies., Structural and functional analysis of the P.1 variant of SARS-CoV-2 from Brazil reveals less resistance to antibodies generated from natural infection or vaccination compared to another similar variant, B.1.351. A monoclonal antibody mAb 222 is able to neutralize all three variants (P.1, B.1.351 and B.1.1.7), with its light chain able to restore neutralization potency to broad group of antibodies.

Published
2021

41. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Author

Christina Dold, Miles W. Carroll, C Mason, David Hall, Eleanor Barnes, Cesar Lopez-Camacho, F. Gomes Naveca, Jingshan Ren, M C Nunes, D. Zhou, David I. Stuart, P Goulder, Elizabeth E. Fry, Neil G. Paterson, Shabir A. Madhi, Juthathip Mongkolsapaya, Amy Flaxman, S A Johnson, Teresa Lambe, Valdinete Alves do Nascimento, Sandra Belij-Rammerstorfer, Alexander J. Mentzer, Helen M. Ginn, Tao Dong, Thomas S. Walter, Donal T. Skelly, Paul Klenerman, Z Ditse, Marilda M. Siqueira, Sarah C. Gilbert, Susanna Dunachie, James C. Knight, Alex Pauvolid-Corrêa, P Supasa, Mark A. Williams, Vicky L. Baillie, N Serafin, C Fernandes da Costa, Yuguang Zhao, Andrew J. Pollard, R Nutalai, S Bibi, T G Ritter, Fabrícia F. Nascimento, M Bittaye, Wanwisa Dejnirattisai, Beibei Wang, Chang Liu, Gavin R. Screaton, Elizabeth A. Clutterbuck, Aekkachai Tuekprakhon, Paola Cristina Resende, J Slon-Campos, S A Costa Clemens, Nigel J. Temperton, Duyvesteyn Hme., D W Crook, K Da Silva, and T Malik

Subjects
Antigen-Antibody Complex, COVID-19 Vaccines, medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Antibodies, Viral, Crystallography, X-Ray, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Neutralization, Article, Protein Domains, Antigen, Neutralization Tests, Chlorocebus aethiops, medicine, Animals, Humans, Vero Cells, COVID-19 Serotherapy, QR355, biology, SARS-CoV-2, Immunization, Passive, Antibodies, Monoclonal, COVID-19, Antibodies, Neutralizing, Virology, Immunization, Spike Glycoprotein, Coronavirus, biology.protein, Vero cell, Antibody
Abstract

SARS-CoV-2 has undergone progressive change with variants conferring advantage rapidly becoming dominant lineages e.g. B.1.617. With apparent increased transmissibility variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the UK. Here we study the ability of monoclonal antibodies, convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2 and complement this with structural analyses of Fab/RBD complexes and map the antigenic space of current variants. Neutralization of both viruses is reduced when compared with ancestral Wuhan related strains but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2 suggesting that individuals previously infected by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insight for immunisation policy with future variant vaccines in non-immune populations., The B.1.617 lineage of SARS-CoV-2, especially the delta strain that is B.1.617.2 has contributed to the wave of infection in the Indian subcontinent. Structural and serological analyses show no evidence of antibody escape but individuals previously infected with either the B.1.351 (beta) and P.1 (gamma) variants are likely more susceptible to reinfection by the delta strain. Vaccines based on B.1.1.7 (alpha) are likely to provide the broadest protection against current variants.

Published
2021

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

Author

Rungtiwa Nutalai, Daming Zhou, Aekkachai Tuekprakhon, Helen M. Ginn, Piyada Supasa, Chang Liu, Jiandong Huo, Alexander J. Mentzer, Helen M.E. Duyvesteyn, Aiste Dijokaite-Guraliuc, Donal Skelly, Thomas G. Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede Constantinides, Hermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, Neil G. Paterson, Mark A. Williams, David R. Hall, Juthathip Mongkolsapaya, Elizabeth E. Fry, Wanwisa Dejnirattisai, Jingshan Ren, David I. Stuart, Gavin R. Screaton, consortium, OPTIC, and consortium, ISARIC4C

Subjects
QR355, Epitopes, COVID-19 Vaccines, Neutralization Tests, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Antibodies, Monoclonal, COVID-19, Humans, Angiotensin-Converting Enzyme 2, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology
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 focused 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

44. Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2

Author

Aekkachai Tuekprakhon, Thomas S. Walter, Donal T. Skelly, Beibei Wang, Marilda M. Siqueira, Thomas A. Bowden, Miles W. Carroll, David Hall, Derrick W. Crook, Susanna Dunachie, Paola Cristina Resende, Julian C. Knight, David I. Stuart, Cesar Lopez-Camacho, Piyada Supasa, Rubin Hulswit, Tao Dong, Guido C. Paesen, J Slon-Campos, S Bibi, Amy Flaxman, Fernanda Nascimento, Neil G. Paterson, Chang Liu, Sarah C. Gilbert, Juthathip Mongkolsapaya, Mark A. Williams, Alex Pauvolid-Corrêa, Paul Klenerman, Sandra Belij-Rammerstorfer, Helen M. Ginn, Eleanor Barnes, Helen M. E. Duyvesteyn, D. Zhou, Teresa Lambe, Valdinete Alves do Nascimento, Elizabeth A. Clutterbuck, Cristiano Fernandes da Costa, Sue Ann Costa Clemens, M Bittaye, Felipe Gomes Naveca, R Levin, R Nutalai, Yuguang Zhao, Andrew J. Pollard, Elizabeth E. Fry, Wanwisa Dejnirattisai, Jingshan Ren, Alexander J. Mentzer, Gavin R. Screaton, and Christina Dold

Subjects
Vaccination, biology, medicine.drug_class, biology.protein, medicine, Antibody, Binding site, Monoclonal antibody, Immunoglobulin light chain, Neutralizing antibody, Virology, Neutralization, Virus
Abstract

SummaryTerminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Published
2021

45. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Author

Liu, Chang, primary, Ginn, Helen M., additional, Dejnirattisai, Wanwisa, additional, Supasa, Piyada, additional, Wang, Beibei, additional, Tuekprakhon, Aekkachai, additional, Nutalai, Rungtiwa, additional, Zhou, Daming, additional, Mentzer, Alexander J., additional, Zhao, Yuguang, additional, Duyvesteyn, Helen M.E., additional, López-Camacho, César, additional, Slon-Campos, Jose, additional, Walter, Thomas S., additional, Skelly, Donal, additional, Johnson, Sile Ann, additional, Ritter, Thomas G., additional, Mason, Chris, additional, Costa Clemens, Sue Ann, additional, Gomes Naveca, Felipe, additional, Nascimento, Valdinete, additional, Nascimento, Fernanda, additional, Fernandes da Costa, Cristiano, additional, Resende, Paola Cristina, additional, Pauvolid-Correa, Alex, additional, Siqueira, Marilda M., additional, Dold, Christina, additional, Temperton, Nigel, additional, Dong, Tao, additional, Pollard, Andrew J., additional, Knight, Julian C., additional, Crook, Derrick, additional, Lambe, Teresa, additional, Clutterbuck, Elizabeth, additional, Bibi, Sagida, additional, Flaxman, Amy, additional, Bittaye, Mustapha, additional, Belij-Rammerstorfer, Sandra, additional, Gilbert, Sarah C., additional, Malik, Tariq, additional, Carroll, Miles W., additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Baillie, Vicky, additional, Serafin, Natali, additional, Ditse, Zanele, additional, Da Silva, Kelly, additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Madhi, Shabir, additional, Nunes, Marta C., additional, Goulder, Philip, additional, Fry, Elizabeth E., additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Stuart, David I., additional, and Screaton, Gavin R., additional

Published
2021
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46. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Author

Derrick W. Crook, Eleanor Barnes, Naomi Coombes, D. Zhou, Jingshan Ren, Duyvesteyn Hme., Bassam Hallis, Alexander J. Mentzer, Christina Dold, Sheila F Lumley, Cesar Lopez-Camacho, Aekkachai Tuekprakhon, Elizabeth E. Fry, Guido C. Paesen, Thomas S. Walter, Donal T. Skelly, Beibei Wang, Helen M. Ginn, David I. Stuart, Chang Liu, Sandra Belij-Rammerstorfer, Julian C. Knight, Susanna Dunachie, Juthathip Mongkolsapaya, S Bibi, Teresa Lambe, Amy Flaxman, Sarah C. Gilbert, P Supasa, Wanwisa Dejnirattisai, Paul Klenerman, M Bittaye, Miles W. Carroll, Tao Dong, Sue Charlton, R Levin, R Nutalai, Yuguang Zhao, William James, Gavin R. Screaton, Kevin R. Bewley, Elizabeth A. Clutterbuck, J Slon-Campos, and Andrew J. Pollard

Subjects
Models, Molecular, COVID-19 Vaccines, medicine.drug_class, Plasma protein binding, Biology, Monoclonal antibody, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Neutralization, 03 medical and health sciences, 0302 clinical medicine, Neutralization Tests, Chlorocebus aethiops, medicine, Animals, Humans, Receptor, Vero Cells, COVID-19 Serotherapy, 030304 developmental biology, 0303 health sciences, Mutation, Clinical Trials as Topic, SARS-CoV-2, HEK 293 cells, Immunization, Passive, Antibodies, Monoclonal, COVID-19, Virology, HEK293 Cells, biology.protein, Vero cell, Antibody, 030217 neurology & neurosurgery, Protein Binding
Abstract

The race to produce vaccines against SARS-CoV-2 began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK–B.1.1.7, South Africa–B.1.351 and Brazil–P.1. These variants have multiple changes in the immunodominant spike protein which facilitates viral cell entry via the Angiotensin converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant., Structure-function analysis of the SARS-CoV-2 variant B.1.351 using serum samples from convalescent and vaccinated individuals reveals how mutations in the viral spike protein result in tighter binding to the receptor ACE2 and allow escape from monoclonal antibody neutralization.

Published
2021

47. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Author

Aekkachai Tuekprakhon, Amy Flaxman, Sarah C. Gilbert, Mark A. Williams, Teresa Lambe, Guido C. Paesen, J Slon-Campos, Eleanor Barnes, William James, N Gent, Naomi Coombes, I Shaik, Sue Charlton, Andrew J. Pollard, Christina Dold, Sheila F Lumley, A Sienkiewicz, Bassam Hallis, Alexander J. Mentzer, D. Zhou, Elizabeth E. Fry, R Nutalai, Kerry J Godwin, Gavin R. Screaton, Cesar Lopez-Camacho, Kevin R. Bewley, Paul Klenerman, Elizabeth A. Clutterbuck, Miles W. Carroll, Wanwisa Dejnirattisai, S Bibi, Beibei Wang, Juthathip Mongkolsapaya, Susanna Dunachie, Sandra Belij-Rammerstorfer, Jingshan Ren, David R. Hall, R Levin, Thomas S. Walter, Donal T. Skelly, Natalie Baker, Helen M. Ginn, P Supasa, Tao Dong, Chang Liu, Neil G. Paterson, Yuguang Zhao, Julian C. Knight, Holly E. Humphries, M Bittaye, David I. Stuart, D W Crook, and Duyvesteyn Hme.

Subjects
medicine.drug_class, CHO Cells, Biology, Antibodies, Viral, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Neutralization, Virus, Article, Structure-Activity Relationship, 03 medical and health sciences, Cricetulus, 0302 clinical medicine, Chlorocebus aethiops, medicine, Animals, Humans, Pandemics, Vero Cells, 030304 developmental biology, Vaccines, 0303 health sciences, SARS-CoV-2, Transmission (medicine), Antibodies, Monoclonal, COVID-19, Antibodies, Neutralizing, Research Highlight, Virology, Vaccination, HEK293 Cells, Viral replication, Spike Glycoprotein, Coronavirus, Vero cell, biology.protein, Infectious diseases, Antibody, 030217 neurology & neurosurgery, Protein Binding
Abstract

SARS-CoV-2 has caused over 2M deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbours 9 amino-acid changes in the spike, including N501Y in the ACE2 interacting-surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterised monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed., The SARS-CoV-2 B.1.1.7 variant is not neutralized as easily as the original form of the virus. Some public antibodies cannot neutralize B.1.1.7, due to altered light chain contacts with residue 501. However, B.1.1.7 does not show widespread escape from monoclonal antibodies, natural antibody responses, or vaccines.

Published
2021

48. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa

Author

Acharaporn Dambua, Areerat Khorchai, Adisak Trinavarat, Aekkachai Tuekprakhon, Phitchapa Pongpaksupasin, Patcharaporn Boonchu, Mongkol Uiprasertkul, Chonlada Yodtup, Panya Luksanapruksa, La-ongsri Atchaneeyasakul, Monchai Ruangchainikom, Somchai Sangkitporn, Aulia Rahmi Pawestri, Visit Vamvanij, and Siripakorn Sangkitporn

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Retinitis pigmentosa (RP), Medicine (miscellaneous), Phases of clinical research, Disease, Mesenchymal Stem Cell Transplantation, Biochemistry, Genetics and Molecular Biology (miscellaneous), Transplantation, Autologous, Retina, lcsh:Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Inherited retinal diseases, Internal medicine, Retinitis pigmentosa, medicine, Humans, lcsh:QD415-436, Adverse effect, Mesenchymal stem cell, lcsh:R5-920, Stem cell therapy, business.industry, Research, Mesenchymal Stem Cells, Cell Biology, Stem-cell therapy, medicine.disease, Transplantation, 030104 developmental biology, Intravitreal Injections, 030221 ophthalmology & optometry, Phase I clinical trial, Molecular Medicine, Stem cell, business, lcsh:Medicine (General), Retinitis Pigmentosa
Abstract

Background Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. Methods This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. Results During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. Conclusion Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. Trial registration ClinicalTrials.gov, NCT01531348. Registered on February 10, 2012

Published
2021

49. Additional file 1 of Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa

Author

Aekkachai Tuekprakhon, Siripakorn Sangkitporn, Adisak Trinavarat, Aulia Rahmi Pawestri, Visit Vamvanij, Monchai Ruangchainikom, Panya Luksanapruksa, Phitchapa Pongpaksupasin, Areerat Khorchai, Acharaporn Dambua, Patcharaporn Boonchu, Chonlada Yodtup, Mongkol Uiprasertkul, Somchai Sangkitporn, and Atchaneeyasakul, La-Ongsri

Subjects
InformationSystems_MODELSANDPRINCIPLES, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

Additional file 1: S1 Table. Best corrected visual acuity (logMAR).

Published
2021
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50. Reduced Neutralization of SARS-CoV-2 B.1.1.7 Variant from Naturally Acquired and Vaccine Induced Antibody Immunity

Author

Piyada Supasa, Daming Zhou, Wanwisa Dejnirattisai, Chang Liu, Alexander J. Mentzer, Helen M. Ginn, Yuguang Zhao, Helen ME Duyvesteyn, Rungtiwa Nutalai, Aekkachai Tuekprakhon, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, Cesar Lopez-Camacho, Bassam Hallis, Naomi Coombes, Kevin Bewley, Sue Charlton, Thomas S. Walter, Eleanor Barnes, Susanna Dunachie, Donal Skelly, Sheila Lumley, Natalie Baker, Imam Shaik, Holly Humphries, Kerry Godwin, Nick Gent, Alex Sienkiewicz, Christina Dold, Robert Levin, Tao Dong, Andrew Pollard, Julian Knight, Paul Klenerman, Derrick W. Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-rammerstorfer, Sarah C. Gilbert, David R. Hall, Mark A. Williams, Neil G. Paterson, William James, Miles W. Carroll, Elizabeth E. Fry, Juthathip Mongkolspaya, Jingshan Ren, David I. Stuart, and Gavin R. Screaton

Published
2021

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