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2. Cancer tissue of origin constrains the growth and metabolism of metastases

Author

Sivanand, Sharanya, Gultekin, Yetis, Winter, Peter S., Vermeulen, Sidney Y., Tchourine, Konstantine M., Abbott, Keene L., Danai, Laura V., Gourgue, Florian, Do, Brian T., Crowder, Kayla, Kunchok, Tenzin, Lau, Allison N., Darnell, Alicia M., Jefferson, Alexandria, Morita, Satoru, Duda, Dan G., Aguirre, Andrew J., Wolpin, Brian M., Henning, Nicole, Spanoudaki, Virginia, Maiorino, Laura, Irvine, Darrell J., Yilmaz, Omer H., Lewis, Caroline A., Vitkup, Dennis, Shalek, Alex K., and Vander Heiden, Matthew G.

Published
2024
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4. Priming antibody responses to the fusion peptide in rhesus macaques

Author

Cottrell, Christopher A., Pratap, Payal P., Cirelli, Kimberly M., Carnathan, Diane G., Enemuo, Chiamaka A., Antanasijevic, Aleksandar, Ozorowski, Gabriel, Sewall, Leigh M., Gao, Hongmei, Allen, Joel D., Nogal, Bartek, Silva, Murillo, Bhiman, Jinal, Pauthner, Matthias, Irvine, Darrell J., Montefiori, David, Crispin, Max, Burton, Dennis R., Silvestri, Guido, Crotty, Shane, and Ward, Andrew B.

Published
2024
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8. Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques

Author

He, Wan-Ting, Yuan, Meng, Callaghan, Sean, Musharrafieh, Rami, Song, Ge, Silva, Murillo, Beutler, Nathan, Lee, Wen-Hsin, Yong, Peter, Torres, Jonathan L, Melo, Mariane, Zhou, Panpan, Zhao, Fangzhu, Zhu, Xueyong, Peng, Linghang, Huang, Deli, Anzanello, Fabio, Ricketts, James, Parren, Mara, Garcia, Elijah, Ferguson, Melissa, Rinaldi, William, Rawlings, Stephen A, Nemazee, David, Smith, Davey M, Briney, Bryan, Safonova, Yana, Rogers, Thomas F, Dan, Jennifer M, Zhang, Zeli, Weiskopf, Daniela, Sette, Alessandro, Crotty, Shane, Irvine, Darrell J, Ward, Andrew B, Wilson, Ian A, Burton, Dennis R, and Andrabi, Raiees

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related, Pneumonia & Influenza, Emerging Infectious Diseases, Biotechnology, Biodefense, Prevention, Immunization, Vaccine Related (AIDS), Pneumonia, Lung, Infectious Diseases, Infection, Good Health and Well Being, Animals, Antibodies, Neutralizing, Antibodies, Viral, Broadly Neutralizing Antibodies, COVID-19, Epitopes, Humans, Macaca mulatta, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.

Published
2022

10. A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates

Author

Phung, Ivy, Rodrigues, Kristen A., Marina-Zárate, Ester, Maiorino, Laura, Pahar, Bapi, Lee, Wen-Hsin, Melo, Mariane, Kaur, Amitinder, Allers, Carolina, Fahlberg, Marissa, Grasperge, Brooke F., Dufour, Jason P., Schiro, Faith, Aye, Pyone P., Lopez, Paul G., Torres, Jonathan L., Ozorowski, Gabriel, Eskandarzadeh, Saman, Kubitz, Michael, Georgeson, Erik, Groschel, Bettina, Nedellec, Rebecca, Bick, Michael, Kaczmarek Michaels, Katarzyna, Gao, Hongmei, Shen, Xiaoying, Carnathan, Diane G., Silvestri, Guido, Montefiori, David C., Ward, Andrew B., Hangartner, Lars, Veazey, Ronald S., Burton, Dennis R., Schief, William R., Irvine, Darrell J., and Crotty, Shane

Published
2023
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12. ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer

Author

Mota, Ines, Patrucco, Enrico, Mastini, Cristina, Mahadevan, Navin R., Thai, Tran C., Bergaggio, Elisa, Cheong, Taek-Chin, Leonardi, Giulia, Karaca-Atabay, Elif, Campisi, Marco, Poggio, Teresa, Menotti, Matteo, Ambrogio, Chiara, Longo, Dario L., Klaeger, Susan, Keshishian, Hasmik, Sztupinszki, Zsófia M., Szallasi, Zoltan, Keskin, Derin B., Duke-Cohan, Jonathan S., Reinhold, Bruce, Carr, Steven A., Wu, Catherine J., Moynihan, Kelly D., Irvine, Darrell J., Barbie, David A., Reinherz, Ellis L., Voena, Claudia, Awad, Mark M., Blasco, Rafael B., and Chiarle, Roberto

Published
2023
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18. Long-primed germinal centres with enduring affinity maturation and clonal migration

Author

Lee, Jeong Hyun, Sutton, Henry J., Cottrell, Christopher A., Phung, Ivy, Ozorowski, Gabriel, Sewall, Leigh M., Nedellec, Rebecca, Nakao, Catherine, Silva, Murillo, Richey, Sara T., Torre, Jonathan L., Lee, Wen-Hsin, Georgeson, Erik, Kubitz, Michael, Hodges, Sam, Mullen, Tina-Marie, Adachi, Yumiko, Cirelli, Kimberly M., Kaur, Amitinder, Allers, Carolina, Fahlberg, Marissa, Grasperge, Brooke F., Dufour, Jason P., Schiro, Faith, Aye, Pyone P., Kalyuzhniy, Oleksandr, Liguori, Alessia, Carnathan, Diane G., Silvestri, Guido, Shen, Xiaoying, Montefiori, David C., Veazey, Ronald S., Ward, Andrew B., Hangartner, Lars, Burton, Dennis R., Irvine, Darrell J., Schief, William R., and Crotty, Shane

Published
2022
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20. Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

Author

Dalvie, Neil C., Rodriguez-Aponte, Sergio A., Hartwell, Brittany L., Tostanoski, Lisa H., Biedermann, Andrew M., Crowell, Laura E., Kaur, Kawaljit, Kumru, Ozan S., Carter, Lauren, Yu, Jingyou, Chang, Aiquan, McMahan, Katherine, Courant, Thomas, Lebas, Celia, Lemnios, Ashley A., Rodrigues, Kristen A., Silva, Murillo, Johnston, Ryan S., Naranjo, Christopher A., Tracey, Mary Kate, Brady, Joseph R., Whittaker, Charles A., Yun, Dongsoo, Brunette, Natalie, Wang, Jing Yang, Walkey, Carl, Fiala, Brooke, Kar, Swagata, Porto, Maciel, Lok, Megan, Andersen, Hanne, Lewis, Mark G., Love, Kerry R., Camp, Danielle L., Silverman, Judith Maxwell, Kleanthous, Harry, Joshi, Sangeeta B., Volkin, David B., Dubois, Patrice M., Collin, Nicolas, King, Neil P., Barouch, Dan H., Irvine, Darrell J., and Love, J. Christopher

Published
2021

23. Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques

Author

Escolano, Amelia, Gristick, Harry B, Abernathy, Morgan E, Merkenschlager, Julia, Gautam, Rajeev, Oliveira, Thiago Y, Pai, Joy, West, Anthony P, Barnes, Christopher O, Cohen, Alexander A, Wang, Haoqing, Golijanin, Jovana, Yost, Daniel, Keeffe, Jennifer R, Wang, Zijun, Zhao, Peng, Yao, Kai-Hui, Bauer, Jens, Nogueira, Lilian, Gao, Han, Voll, Alisa V, Montefiori, David C, Seaman, Michael S, Gazumyan, Anna, Silva, Murillo, McGuire, Andrew T, Stamatatos, Leonidas, Irvine, Darrell J, Wells, Lance, Martin, Malcolm A, Bjorkman, Pamela J, and Nussenzweig, Michel C

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Immunization, Vaccine Related (AIDS), Prevention, Biotechnology, HIV/AIDS, Vaccine Related, Infectious Diseases, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, AIDS Vaccines, Amino Acid Sequence, Animals, Antibodies, Neutralizing, Antibody Affinity, Antibody Specificity, Antigen-Antibody Complex, B-Lymphocytes, Cell Proliferation, Clone Cells, Cloning, Molecular, Cross-Priming, Cryoelectron Microscopy, Female, HIV Antibodies, HIV-1, Immunodominant Epitopes, Lymphocyte Activation, Macaca mulatta, Male, Mice, Models, Molecular, Polysaccharides, Rabbits, Somatic Hypermutation, Immunoglobulin, Vaccination, General Science & Technology
Abstract

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.

Published
2019

27. Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response.

Author

Bhagchandani, Sachin H., Yang, Leerang, Lam, Jonathan H., Maiorino, Laura, Ben-Akiva, Elana, Rodrigues, Kristen A., Romanov, Anna, Suh, Heikyung, Aung, Aereas, Wu, Shengwei, Wadhera, Anika, Chakraborty, Arup K., and Irvine, Darrell J.

Subjects
FOLLICULAR dendritic cells, PEPTIDE vaccines, T helper cells, HUMORAL immunity, B cells
Abstract

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased TFH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of TFH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines. Editor's summary: A key feature of effective vaccines is that the delivery strategy optimizes immune responses. Bhagchandani et al. sought to optimize immune responses using prolonged exposure to a protein subunit vaccine called escalating-dose immunization (EDI). They immunized mice with an adjuvanted HIV envelope protein subunit and tested different numbers of doses, dose ratios, and time intervals between doses. A two-dose regimen for which 20% of the vaccine was administered in the first dose and 80% was given in the second dose 7 days later induced effective follicular helper T cell and antigen-specific germinal center B cell responses that were also reflected in higher antibody titers. This response was linked to enhanced antigen capture and presentation by dendritic cells. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Published
2024
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29. Polymers at the Interface with Biology

Author

Deming, Timothy J, Klok, Harm-Anton, Armes, Steven P, Becker, Matthew L, Champion, Julie A, Chen, Eugene Y-X, Heilshorn, Sarah C, van Hest, Jan CM, Irvine, Darrell J, Johnson, Jeremiah A, Kiessling, Laura L, Maynard, Heather D, de la Cruz, Monica Olvera, Sullivan, Millicent O, Tirrell, Matthew V, Anseth, Kristi S, Lecommandoux, Sebastien, Percec, Simona, Zhong, Zhiyuan, and Albertsson, Ann-Christine

Subjects
Biocompatible Materials, Bioengineering, Nanoparticles, Chemical Sciences, Biological Sciences, Engineering, Polymers
Published
2018

30. Structure–Property Relationships of Amphiphilic Nanoparticles That Penetrate or Fuse Lipid Membranes

Author

Atukorale, Prabhani U, Guven, Zekiye P, Bekdemir, Ahmet, Carney, Randy P, Van Lehn, Reid C, Yun, Dong Soo, Silva, Paulo H Jacob, Demurtas, Davide, Yang, Yu-Sang, Alexander-Katz, Alfredo, Stellacci, Francesco, and Irvine, Darrell J

Subjects
Nanotechnology, Bioengineering, Boron Compounds, Hydrophobic and Hydrophilic Interactions, Ligands, Lipid Bilayers, Liposomes, Membrane Fusion, Nanoparticles, Particle Size, Permeability, Static Electricity, Structure-Activity Relationship, Medicinal and Biomolecular Chemistry, Organic Chemistry, Biochemistry and Cell Biology
Abstract

The development of synthetic nanomaterials that could embed within, penetrate, or induce fusion between membranes without permanent disruption would have great significance for biomedical applications. Here we describe structure-function relationships of highly water-soluble gold nanoparticles comprised of an ∼1.5-5 nm diameter metal core coated by an amphiphilic organic ligand shell, which exhibit membrane embedding and fusion activity mediated by the surface ligands. Using an environment-sensitive dye anchored within the ligand shell as a sensor of membrane embedding, we demonstrate that particles with core sizes of ∼2-3 nm are capable of embedding within and penetrating fluid bilayers. At the nanoscale, these particles also promote spontaneous fusion of liposomes or spontaneously embed within intact liposomal vesicles. These studies provide nanoparticle design and selection principles that could be used in drug delivery applications, as membrane stains, or for the creation of novel organic/inorganic nanomaterial self-assemblies.

Published
2018

32. Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons

Author

Truex, Nicholas L., primary, Mohapatra, Somesh, additional, Melo, Mariane, additional, Rodriguez, Jacob, additional, Li, Na, additional, Abraham, Wuhbet, additional, Sementa, Deborah, additional, Touti, Faycal, additional, Keskin, Derin B., additional, Wu, Catherine J., additional, Irvine, Darrell J., additional, Gómez-Bombarelli, Rafael, additional, and Pentelute, Bradley L., additional

Published
2024
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35. Nanoscience and Nanotechnology Cross Borders.

Author

Khademhosseini, Ali, Chan, Warren WC, Chhowalla, Manish, Glotzer, Sharon C, Gogotsi, Yury, Hafner, Jason H, Hammond, Paula T, Hersam, Mark C, Javey, Ali, Kagan, Cherie R, Kotov, Nicholas A, Lee, Shuit-Tong, Li, Yan, Möhwald, Helmuth, Mulvaney, Paul A, Nel, Andre E, Parak, Wolfgang J, Penner, Reginald M, Rogach, Andrey L, Schaak, Raymond E, Stevens, Molly M, Wee, Andrew TS, Brinker, Jeffrey, Chen, Xiaoyuan, Chi, Lifeng, Crommie, Michael, Dekker, Cees, Farokhzad, Omid, Gerber, Christoph, Ginger, David S, Irvine, Darrell J, Kiessling, Laura L, Kostarelos, Kostas, Landes, Christy, Lee, Takhee, Leggett, Graham J, Liang, Xing-Jie, Liz-Marzán, Luis, Millstone, Jill, Odom, Teri W, Ozcan, Aydogan, Prato, Maurizio, Rao, CNR, Sailor, Michael J, Weiss, Emily, and Weiss, Paul S

Subjects
Nanoscience & Nanotechnology
Published
2017

37. Author Correction: Long-primed germinal centres with enduring affinity maturation and clonal migration

Author

Lee, Jeong Hyun, Sutton, Henry J., Cottrell, Christopher A., Phung, Ivy, Ozorowski, Gabriel, Sewall, Leigh M., Nedellec, Rebecca, Nakao, Catherine, Silva, Murillo, Richey, Sara T., Torres, Jonathan L., Lee, Wen-Hsin, Georgeson, Erik, Kubitz, Michael, Hodges, Sam, Mullen, Tina-Marie, Adachi, Yumiko, Cirelli, Kimberly M., Kaur, Amitinder, Allers, Carolina, Fahlberg, Marissa, Grasperge, Brooke F., Dufour, Jason P., Schiro, Faith, Aye, Pyone P., Kalyuzhniy, Oleksandr, Liguori, Alessia, Carnathan, Diane G., Silvestri, Guido, Shen, Xiaoying, Montefiori, David C., Veazey, Ronald S., Ward, Andrew B., Hangartner, Lars, Burton, Dennis R., Irvine, Darrell J., Schief, William R., and Crotty, Shane

Published
2023
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38. Glycan-costumed virus-like particles promote type 1 anti-tumor immunity

Author

Lensch, Valerie, primary, Gabba, Adele, additional, Hincapie, Robert, additional, Bhagchandani, Sachin H., additional, Basak, Ankit, additional, Alam, Mohammad Murshid, additional, Irvine, Darrell J., additional, Shalek, Alex K., additional, Johnson, Jeremiah A., additional, Finn, M. G., additional, and Kiessling, Laura L., additional

Published
2024
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40. Local delivery of cell surface-targeted immunocytokines programs systemic anti-tumor immunity

Author

Santollani, Luciano, primary, Zhang, Yiming J., additional, Maiorino, Laura, additional, Palmeri, Joseph R., additional, Stinson, Jordan A., additional, Duhamel, Lauren R., additional, Qureshi, Kashif, additional, Suggs, Jack R., additional, Porth, Owen T., additional, Pinney, William, additional, Msari, Riyam Al, additional, Dane Wittrup, K., additional, and Irvine, Darrell J., additional

Published
2024
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47. Engineered immunogen binding to alum adjuvant enhances humoral immunity

Author

Moyer, Tyson J., Kato, Yu, Abraham, Wuhbet, Chang, Jason Y. H., Kulp, Daniel W., Watson, Nicki, Turner, Hannah L., Menis, Sergey, Abbott, Robert K., Bhiman, Jinal N., Melo, Mariane B., Simon, Hayley A., Herrera-De la Mata, Sara, Liang, Shu, Seumois, Gregory, Agarwal, Yash, Li, Na, Burton, Dennis R., Ward, Andrew B., Schief, William R., Crotty, Shane, and Irvine, Darrell J.

Published
2020
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48. Influence of the glycocalyx and plasma membrane composition on amphiphilic gold nanoparticle association with erythrocytes

Author

Atukorale, Prabhani U, Yang, Yu-Sang, Bekdemir, Ahmet, Carney, Randy P, Silva, Paulo J, Watson, Nicki, Stellacci, Francesco, and Irvine, Darrell J

Subjects
Bioengineering, Nanotechnology, Underpinning research, 1.1 Normal biological development and functioning, Erythrocyte Membrane, Glycocalyx, Gold, Humans, Metal Nanoparticles, Physical Sciences, Chemical Sciences, Technology, Nanoscience & Nanotechnology
Abstract

Erythrocytes are attractive as potential cell-based drug carriers because of their abundance and long lifespan in vivo. Existing methods for loading drug cargos into erythrocytes include hypotonic treatments, electroporation, and covalent attachment onto the membrane, all of which require ex vivo manipulation. Here, we characterized the properties of amphiphilic gold nanoparticles (amph-AuNPs), comprised of a ∼2.3 nm gold core and an amphiphilic ligand shell, which are able to embed spontaneously within erythrocyte membranes and might provide a means to load drugs into red blood cells (RBCs) directly in vivo. Particle interaction with RBC membranes occurred rapidly at physiological temperature. We further show that amph-AuNP uptake by RBCs was limited by the glycocalyx and was particularly influenced by sialic acids on cell surface proteoglycans. Using a reductionist model membrane system with synthetic lipid vesicles, we confirmed the importance of membrane fluidity and the glycocalyx in regulating amph-AuNP/membrane interactions. These results thus provide evidence for the interaction of amph-AuNPs with erythrocyte membranes and identify key membrane components that govern this interaction, providing a framework for the development of amph-AuNP-carrying erythrocyte 'pharmacytes' in vivo.

Published
2015

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