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

Author

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

Published
2024
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3. A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Author

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

Published
2024
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4. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

Author

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

Published
2023
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5. 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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6. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author

Conlon, Christopher, Deeks, Alexandra, Frater, John, Frending, Lisa, Gardiner, Siobhan, Jämsén, Anni, Jeffery, Katie, Malone, Tom, Phillips, Eloise, Rothwell, Lucy, Stafford, Lizzie, Tuekprakhon, Aekkachai, 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, 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., Huo, Jiandong, Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2022
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10. Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

Author

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

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

Author

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

Abstract

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

Published
2023

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

Author

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

Abstract

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

Published
2023

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

Author

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

Published
2023
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17. Isolation of a pair of potent broadly neutralizing mAb binding to RBD and SD1 domains of SARS-CoV-2

Author

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

Published
2023
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18. 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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19. 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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20. 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

22. A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques

Author

Jones, Andrew T., primary, Chamcha, Venkateswarlu, additional, Kesavardhana, Sannula, additional, Shen, Xiaoying, additional, Beaumont, David, additional, Das, Raksha, additional, Wyatt, Linda S., additional, LaBranche, Celia C., additional, Stanfield-Oakley, Sherry, additional, Ferrari, Guido, additional, Montefiori, David C., additional, Moss, Bernard, additional, Tomaras, Georgia D., additional, Varadarajan, Raghavan, additional, and Amara, Rama Rao, additional

Published
2018
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23. Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library

Author

Khan, Lubina, primary, Kumar, Rajesh, additional, Thiruvengadam, Ramachandran, additional, Parray, Hilal Ahmad, additional, Makhdoomi, Muzamil Ashraf, additional, Kumar, Sanjeev, additional, Aggarwal, Heena, additional, Mohata, Madhav, additional, Hussain, Abdul Wahid, additional, Das, Raksha, additional, Varadarajan, Raghavan, additional, Bhattacharya, Jayanta, additional, Vajpayee, Madhu, additional, Murugavel, K. G., additional, Solomon, Suniti, additional, Sinha, Subrata, additional, and Luthra, Kalpana, additional

Published
2017
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24. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75

Author

Huo, Jiandong, Dijokaite-Guraliuc, Aiste, Liu, Chang, Das, Raksha, Supasa, Piyada, Selvaraj, Muneeswaran, Nutalai, Rungtiwa, Zhou, Daming, 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.

Abstract

Variants of 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 the 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 to 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 BA.2.75 is now the dominant variant. ACE2 affinity appears to be prioritised over greater escape.

Published
2022
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