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1. 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 BA.1 dominated the initial wave but has been replaced by BA.2 in many countries.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

2. 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

3. 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

4. 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

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

Author

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

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.

Published
2021

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

Author

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

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.

Published
2021

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

Author

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

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.

Published
2021

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

Author

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

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.

Published
2021

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