Search

Your search keyword '"di Iulio, Julia' showing total 12 results
Start Over Author "di Iulio, Julia Database OAIster
12 results on '"di Iulio, Julia'

1. Predicting the mutational drivers of future SARS-CoV-2 variants of concern

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Mathematics, Maher, M Cyrus, Bartha, Istvan, Weaver, Steven, di Iulio, Julia, Ferri, Elena, Soriaga, Leah, Lempp, Florian A, Hie, Brian L, Bryson, Bryan, Berger, Bonnie, Robertson, David L, Snell, Gyorgy, Corti, Davide, Virgin, Herbert W, Kosakovsky Pond, Sergei L, Telenti, Amalio, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Mathematics, Maher, M Cyrus, Bartha, Istvan, Weaver, Steven, di Iulio, Julia, Ferri, Elena, Soriaga, Leah, Lempp, Florian A, Hie, Brian L, Bryson, Bryan, Berger, Bonnie, Robertson, David L, Snell, Gyorgy, Corti, Davide, Virgin, Herbert W, Kosakovsky Pond, Sergei L, and Telenti, Amalio

Abstract

SARS-CoV-2 evolution threatens vaccine- and natural infection–derived immunity and the efficacy of therapeutic antibodies. To improve public health preparedness, we sought to predict which existing amino acid mutations in SARS-CoV-2 might contribute to future variants of concern. We tested the predictive value of features comprising epidemiology, evolution, immunology, and neural network–based protein sequence modeling and identified primary biological drivers of SARS-CoV-2 intrapandemic evolution. We found evidence that ACE2-mediated transmissibility and resistance to population-level host immunity has waxed and waned as a primary driver of SARS-CoV-2 evolution over time. We retroactively identified with high accuracy (area under the receiver operator characteristic curve = 0.92 to 0.97) mutations that will spread, at up to 4 months in advance, across different phases of the pandemic. The behavior of the model was consistent with a plausible causal structure where epidemiological covariates combine the effects of diverse and shifting drivers of viral fitness. We applied our model to forecast mutations that will spread in the future and characterize how these mutations affect the binding of therapeutic antibodies. These findings demonstrate that it is possible to forecast the driver mutations that could appear in emerging SARS-CoV-2 variants of concern. We validated this result against Omicron, showing elevated predictive scores for its component mutations before emergence and rapid score increase across daily forecasts during emergence. This modeling approach may be applied to any rapidly evolving pathogens with sufficiently dense genomic surveillance data, such as influenza, and unknown future pandemic viruses.

Published
2022

2. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author

Park, Young-Jun, Pinto, Dora, Walls, Alexandra C, Liu, Zhuoming, De Marco, Anna, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R, Addetia, Amin, Bowen, John E, Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A, Franko, Nicholas M, Logue, Jennifer K, Dang, Ha V, Hauser, Kevin, di Iulio, Julia, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi, Farhat, Nisar, Kaiser, Hannah, Montiel-Ruiz, Martin, Noack, Julia, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, De Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, Corti, Davide; https://orcid.org/0000-0002-5797-1364, Park, Young-Jun, Pinto, Dora, Walls, Alexandra C, Liu, Zhuoming, De Marco, Anna, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R, Addetia, Amin, Bowen, John E, Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A, Franko, Nicholas M, Logue, Jennifer K, Dang, Ha V, Hauser, Kevin, di Iulio, Julia, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi, Farhat, Nisar, Kaiser, Hannah, Montiel-Ruiz, Martin, Noack, Julia, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, De Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, and Corti, Davide; https://orcid.org/0000-0002-5797-1364

Abstract

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

Published
2022

3. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author

Park, Young-Jun; https://orcid.org/0000-0003-2901-6949, Pinto, Dora, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Liu, Zhuoming; https://orcid.org/0000-0001-8198-0976, De Marco, Anna; https://orcid.org/0000-0001-9641-4838, Benigni, Fabio; https://orcid.org/0000-0002-1974-5606, Zatta, Fabrizia; https://orcid.org/0000-0003-4945-8058, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Sprouse, Kaitlin R; https://orcid.org/0000-0003-0007-2226, Addetia, Amin; https://orcid.org/0000-0001-6703-3841, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Stewart, Cameron; https://orcid.org/0000-0002-2786-6256, Giurdanella, Martina, Saliba, Christian; https://orcid.org/0000-0003-0100-6976, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Schmid, Michael A; https://orcid.org/0000-0002-1137-9322, Franko, Nicholas M; https://orcid.org/0000-0001-8165-6332, Logue, Jennifer K; https://orcid.org/0000-0002-7889-8960, Dang, Ha V; https://orcid.org/0000-0003-1173-9241, Hauser, Kevin, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi; https://orcid.org/0000-0002-4231-3422, Farhat, Nisar; https://orcid.org/0000-0003-0905-7479, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Montiel-Ruiz, Martin; https://orcid.org/0000-0001-6200-9578, Noack, Julia; https://orcid.org/0000-0002-9113-8181, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, de Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, Corti, Davide; https://orcid.org/0000-0002-5797-1364, Park, Young-Jun; https://orcid.org/0000-0003-2901-6949, Pinto, Dora, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Liu, Zhuoming; https://orcid.org/0000-0001-8198-0976, De Marco, Anna; https://orcid.org/0000-0001-9641-4838, Benigni, Fabio; https://orcid.org/0000-0002-1974-5606, Zatta, Fabrizia; https://orcid.org/0000-0003-4945-8058, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Sprouse, Kaitlin R; https://orcid.org/0000-0003-0007-2226, Addetia, Amin; https://orcid.org/0000-0001-6703-3841, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Stewart, Cameron; https://orcid.org/0000-0002-2786-6256, Giurdanella, Martina, Saliba, Christian; https://orcid.org/0000-0003-0100-6976, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Schmid, Michael A; https://orcid.org/0000-0002-1137-9322, Franko, Nicholas M; https://orcid.org/0000-0001-8165-6332, Logue, Jennifer K; https://orcid.org/0000-0002-7889-8960, Dang, Ha V; https://orcid.org/0000-0003-1173-9241, Hauser, Kevin, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi; https://orcid.org/0000-0002-4231-3422, Farhat, Nisar; https://orcid.org/0000-0003-0905-7479, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Montiel-Ruiz, Martin; https://orcid.org/0000-0001-6200-9578, Noack, Julia; https://orcid.org/0000-0002-9113-8181, et al, Ferrari, Paolo, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Giannini, Olivier, de Melo, Guilherme Dias, Lanzavecchia, Antonio, Piccoli, Luca, Pizzuto, Matteo Samuele, and Corti, Davide; https://orcid.org/0000-0002-5797-1364

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development.

Published
2022

4. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

Author

Thomson, Emma C, Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O'Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, Snell, Gyorgy, Thomson, Emma C, Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O'Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, and Snell, Gyorgy

Abstract

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Published
2021

5. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.

Author

Starr, Tyler N, Starr, Tyler N, Czudnochowski, Nadine, Liu, Zhuoming, Zatta, Fabrizia, Park, Young-Jun, Addetia, Amin, Pinto, Dora, Beltramello, Martina, Hernandez, Patrick, Greaney, Allison J, Marzi, Roberta, Glass, William G, Zhang, Ivy, Dingens, Adam S, Bowen, John E, Tortorici, M Alejandra, Walls, Alexandra C, Wojcechowskyj, Jason A, De Marco, Anna, Rosen, Laura E, Zhou, Jiayi, Montiel-Ruiz, Martin, Kaiser, Hannah, Dillen, Josh R, Tucker, Heather, Bassi, Jessica, Silacci-Fregni, Chiara, Housley, Michael P, di Iulio, Julia, Lombardo, Gloria, Agostini, Maria, Sprugasci, Nicole, Culap, Katja, Jaconi, Stefano, Meury, Marcel, Dellota, Exequiel, Abdelnabi, Rana, Foo, Shi-Yan Caroline, Cameroni, Elisabetta, Stumpf, Spencer, Croll, Tristan I, Nix, Jay C, Havenar-Daughton, Colin, Piccoli, Luca, Benigni, Fabio, Neyts, Johan, Telenti, Amalio, Lempp, Florian A, Pizzuto, Matteo S, Chodera, John D, Hebner, Christy M, Virgin, Herbert W, Whelan, Sean PJ, Veesler, David, Corti, Davide, Bloom, Jesse D, Snell, Gyorgy, Starr, Tyler N, Starr, Tyler N, Czudnochowski, Nadine, Liu, Zhuoming, Zatta, Fabrizia, Park, Young-Jun, Addetia, Amin, Pinto, Dora, Beltramello, Martina, Hernandez, Patrick, Greaney, Allison J, Marzi, Roberta, Glass, William G, Zhang, Ivy, Dingens, Adam S, Bowen, John E, Tortorici, M Alejandra, Walls, Alexandra C, Wojcechowskyj, Jason A, De Marco, Anna, Rosen, Laura E, Zhou, Jiayi, Montiel-Ruiz, Martin, Kaiser, Hannah, Dillen, Josh R, Tucker, Heather, Bassi, Jessica, Silacci-Fregni, Chiara, Housley, Michael P, di Iulio, Julia, Lombardo, Gloria, Agostini, Maria, Sprugasci, Nicole, Culap, Katja, Jaconi, Stefano, Meury, Marcel, Dellota, Exequiel, Abdelnabi, Rana, Foo, Shi-Yan Caroline, Cameroni, Elisabetta, Stumpf, Spencer, Croll, Tristan I, Nix, Jay C, Havenar-Daughton, Colin, Piccoli, Luca, Benigni, Fabio, Neyts, Johan, Telenti, Amalio, Lempp, Florian A, Pizzuto, Matteo S, Chodera, John D, Hebner, Christy M, Virgin, Herbert W, Whelan, Sean PJ, Veesler, David, Corti, Davide, Bloom, Jesse D, and Snell, Gyorgy

Abstract

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse sarbecoviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

Published
2021

6. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.

Author

Starr, Tyler N, Starr, Tyler N, Czudnochowski, Nadine, Liu, Zhuoming, Zatta, Fabrizia, Park, Young-Jun, Addetia, Amin, Pinto, Dora, Beltramello, Martina, Hernandez, Patrick, Greaney, Allison J, Marzi, Roberta, Glass, William G, Zhang, Ivy, Dingens, Adam S, Bowen, John E, Tortorici, M Alejandra, Walls, Alexandra C, Wojcechowskyj, Jason A, De Marco, Anna, Rosen, Laura E, Zhou, Jiayi, Montiel-Ruiz, Martin, Kaiser, Hannah, Dillen, Josh R, Tucker, Heather, Bassi, Jessica, Silacci-Fregni, Chiara, Housley, Michael P, di Iulio, Julia, Lombardo, Gloria, Agostini, Maria, Sprugasci, Nicole, Culap, Katja, Jaconi, Stefano, Meury, Marcel, Dellota, Exequiel, Abdelnabi, Rana, Foo, Shi-Yan Caroline, Cameroni, Elisabetta, Stumpf, Spencer, Croll, Tristan I, Nix, Jay C, Havenar-Daughton, Colin, Piccoli, Luca, Benigni, Fabio, Neyts, Johan, Telenti, Amalio, Lempp, Florian A, Pizzuto, Matteo S, Chodera, John D, Hebner, Christy M, Virgin, Herbert W, Whelan, Sean PJ, Veesler, David, Corti, Davide, Bloom, Jesse D, Snell, Gyorgy, Starr, Tyler N, Starr, Tyler N, Czudnochowski, Nadine, Liu, Zhuoming, Zatta, Fabrizia, Park, Young-Jun, Addetia, Amin, Pinto, Dora, Beltramello, Martina, Hernandez, Patrick, Greaney, Allison J, Marzi, Roberta, Glass, William G, Zhang, Ivy, Dingens, Adam S, Bowen, John E, Tortorici, M Alejandra, Walls, Alexandra C, Wojcechowskyj, Jason A, De Marco, Anna, Rosen, Laura E, Zhou, Jiayi, Montiel-Ruiz, Martin, Kaiser, Hannah, Dillen, Josh R, Tucker, Heather, Bassi, Jessica, Silacci-Fregni, Chiara, Housley, Michael P, di Iulio, Julia, Lombardo, Gloria, Agostini, Maria, Sprugasci, Nicole, Culap, Katja, Jaconi, Stefano, Meury, Marcel, Dellota, Exequiel, Abdelnabi, Rana, Foo, Shi-Yan Caroline, Cameroni, Elisabetta, Stumpf, Spencer, Croll, Tristan I, Nix, Jay C, Havenar-Daughton, Colin, Piccoli, Luca, Benigni, Fabio, Neyts, Johan, Telenti, Amalio, Lempp, Florian A, Pizzuto, Matteo S, Chodera, John D, Hebner, Christy M, Virgin, Herbert W, Whelan, Sean PJ, Veesler, David, Corti, Davide, Bloom, Jesse D, and Snell, Gyorgy

Abstract

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse sarbecoviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

Published
2021

7. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

Author

Thomson, Emma C, Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O'Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, Snell, Gyorgy, Thomson, Emma C, Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O'Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, and Snell, Gyorgy

Abstract

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Published
2021

8. Bioinformatics and HIV Latency

Author

Ciuffi, Angela, Mohammadi, Pejman, Golumbeanu, Monica, di Iulio, Julia, Telenti, Amalio, Ciuffi, Angela, Mohammadi, Pejman, Golumbeanu, Monica, di Iulio, Julia, and Telenti, Amalio

Abstract

Despite effective treatment, HIV is not completely eliminated from the infected organism because of the existence of viral reservoirs. A major reservoir consists of infected resting CD4+ T cells, mostly of memory type, that persist over time due to the stable proviral insertion and a longcellular lifespan. Resting cells do not produce viral particles and are protected from viral-induced cytotoxicity or immune killing. However, these latently infected cells can be reactivated by stochastic events or by external stimuli. The present review focuses on novel genome-wide technologies applied to the study of integration, transcriptome, and proteome characteristics and their recent contribution to the understanding of HIV latency.

Published
2021

9. Broad betacoronavirus neutralization by a stem helix–specific human antibody

Author

Pinto, Dora, Sauer, Maximilian M; https://orcid.org/0000-0003-0908-0775, Czudnochowski, Nadine; https://orcid.org/0000-0002-3146-4110, Low, Jun Siong; https://orcid.org/0000-0002-1775-0778, Tortorici, M Alejandra; https://orcid.org/0000-0002-2260-2577, Housley, Michael P, Noack, Julia; https://orcid.org/0000-0002-9113-8181, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Rosen, Laura E; https://orcid.org/0000-0002-8030-0219, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Jerak, Josipa; https://orcid.org/0000-0001-5358-5055, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Islam, Saiful, Jaconi, Stefano, Sprugasci, Nicole; https://orcid.org/0000-0003-3258-5552, Culap, Katja; https://orcid.org/0000-0002-0956-0018, Abdelnabi, Rana; https://orcid.org/0000-0001-9771-7312, Foo, Caroline; https://orcid.org/0000-0002-6380-4917, Coelmont, Lotte; https://orcid.org/0000-0002-7888-4534, Bartha, Istvan; https://orcid.org/0000-0003-3360-1999, Bianchi, Siro; https://orcid.org/0000-0002-5100-8905, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Marzi, Roberta; https://orcid.org/0000-0001-6025-6735, Vetti, Eneida, Cassotta, Antonino; https://orcid.org/0000-0001-8674-4294, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Ferrari, Paolo; https://orcid.org/0000-0002-9619-3104, et al, Pinto, Dora, Sauer, Maximilian M; https://orcid.org/0000-0003-0908-0775, Czudnochowski, Nadine; https://orcid.org/0000-0002-3146-4110, Low, Jun Siong; https://orcid.org/0000-0002-1775-0778, Tortorici, M Alejandra; https://orcid.org/0000-0002-2260-2577, Housley, Michael P, Noack, Julia; https://orcid.org/0000-0002-9113-8181, Walls, Alexandra C; https://orcid.org/0000-0002-9636-8330, Bowen, John E; https://orcid.org/0000-0003-3590-9727, Guarino, Barbara; https://orcid.org/0000-0003-3759-3252, Rosen, Laura E; https://orcid.org/0000-0002-8030-0219, di Iulio, Julia; https://orcid.org/0000-0001-9343-127X, Jerak, Josipa; https://orcid.org/0000-0001-5358-5055, Kaiser, Hannah; https://orcid.org/0000-0002-3991-7401, Islam, Saiful, Jaconi, Stefano, Sprugasci, Nicole; https://orcid.org/0000-0003-3258-5552, Culap, Katja; https://orcid.org/0000-0002-0956-0018, Abdelnabi, Rana; https://orcid.org/0000-0001-9771-7312, Foo, Caroline; https://orcid.org/0000-0002-6380-4917, Coelmont, Lotte; https://orcid.org/0000-0002-7888-4534, Bartha, Istvan; https://orcid.org/0000-0003-3360-1999, Bianchi, Siro; https://orcid.org/0000-0002-5100-8905, Silacci-Fregni, Chiara, Bassi, Jessica; https://orcid.org/0000-0002-4723-6892, Marzi, Roberta; https://orcid.org/0000-0001-6025-6735, Vetti, Eneida, Cassotta, Antonino; https://orcid.org/0000-0001-8674-4294, Ceschi, Alessandro; https://orcid.org/0000-0002-4308-0405, Ferrari, Paolo; https://orcid.org/0000-0002-9619-3104, and et al

Abstract

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

Published
2021

10. Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study

Author

Lubomirov, Rubin, Colombo, Sara, di Iulio, Julia, Ledergerber, Bruno, Martinez, Raquel, Cavassini, Matthias, Hirschel, Bernard, Bernasconi, Enos, Elzi, Luigia, Vernazza, Pietro, Furrer, Hansjakob, Günthard, Huldrych F., Telenti, Amalio, Lubomirov, Rubin, Colombo, Sara, di Iulio, Julia, Ledergerber, Bruno, Martinez, Raquel, Cavassini, Matthias, Hirschel, Bernard, Bernasconi, Enos, Elzi, Luigia, Vernazza, Pietro, Furrer, Hansjakob, Günthard, Huldrych F., and Telenti, Amalio

Abstract

Background. Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. Methods. A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. Results. During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). Conclusions. Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting

Published
2017

11. Bioinformatics and HIV Latency

Author

Ciuffi, Angela, Mohammadi, Pejman, Golumbeanu, Monica, di Iulio, Julia, Telenti, Amalio, Ciuffi, Angela, Mohammadi, Pejman, Golumbeanu, Monica, di Iulio, Julia, and Telenti, Amalio

Abstract

Despite effective treatment, HIV is not completely eliminated from the infected organism because of the existence of viral reservoirs. A major reservoir consists of infected resting CD4+ T cells, mostly of memory type, that persist over time due to the stable proviral insertion and a longcellular lifespan. Resting cells do not produce viral particles and are protected from viral-induced cytotoxicity or immune killing. However, these latently infected cells can be reactivated by stochastic events or by external stimuli. The present review focuses on novel genome-wide technologies applied to the study of integration, transcriptome, and proteome characteristics and their recent contribution to the understanding of HIV latency.

12. Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study

Author

Lubomirov, Rubin, Colombo, Sara, di Iulio, Julia, Ledergerber, Bruno, Martinez, Raquel, Cavassini, Matthias, Hirschel, Bernard, Bernasconi, Enos, Elzi, Luigia, Vernazza, Pietro, Furrer, Hansjakob, Günthard, Huldrych F., Telenti, Amalio, Lubomirov, Rubin, Colombo, Sara, di Iulio, Julia, Ledergerber, Bruno, Martinez, Raquel, Cavassini, Matthias, Hirschel, Bernard, Bernasconi, Enos, Elzi, Luigia, Vernazza, Pietro, Furrer, Hansjakob, Günthard, Huldrych F., and Telenti, Amalio

Abstract

Background. Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. Methods. A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. Results. During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). Conclusions. Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting

Catalog

Books, media, physical & digital resources
See catalog results