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1. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality

Author

Gygi, Jeremy P, Maguire, Cole, Patel, Ravi K, Shinde, Pramod, Konstorum, Anna, Shannon, Casey P, Xu, Leqi, Hoch, Annmarie, Jayavelu, Naresh Doni, Haddad, Elias K, Network, IMPACC, Reed, Elaine F, Kraft, Monica, McComsey, Grace A, Metcalf, Jordan P, Ozonoff, Al, Esserman, Denise, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey B, van Bakel, Harm, Wilson, Michael, Eckalbar, Walter L, Maecker, Holden T, Langelier, Charles R, Steen, Hanno, Altman, Matthew C, Montgomery, Ruth R, Levy, Ofer, Melamed, Esther, Pulendran, Bali, Diray-Arce, Joann, Smolen, Kinga K, Fragiadakis, Gabriela K, Becker, Patrice M, Sekaly, Rafick P, Ehrlich, Lauren IR, Fourati, Slim, Peters, Bjoern, Kleinstein, Steven H, and Guan, Leying

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, COVID-19, Male, Longitudinal Studies, SARS-CoV-2, Female, Middle Aged, Severity of Illness Index, Aged, Adult, Cytokines, Multiomics, IMPACC Network, Adaptive immunity, Innate immunity, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Published
2024

3. IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Author

Ozonoff, Al, Ehrlich, Lauren IR, Melamed, Esther, Sesma, Ana Fernandez, Simon, Viviana, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, McCoey, Grace A, Sekaly, Rafick, Baden, Lindsey R, Levy, Ofer, Schaenman, Joanna, Reed, Elaine F, Shaw, Albert C, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Becker, Patrice M, Augustine, Alison D, Calfee, Carolyn S, Erle, David J, DeBakey, Michael E, Corry, David B, Kheradmand, Farrah, Atkinson, Mark A, Brakenridge, Scott C, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Hough, Catherine L, Messer, William B, Kraft, Monica, Bime, Chris, Peters, Bjoern, Milliren, Carly E, Syphurs, Caitlin, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Liu, Shanshan, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Hayati, Arash Nemati, Bryant, Robert, Abraham, James, Jayavelu, Naresh Doni, Presnell, Scott, Jancsyk, Tomasz, Maguire, Cole, Qi, Jingjing, Lee, Brian, Fourati, Slim, Esserman, Denise A, Guan, Leying, Gygi, Jeremy, Pawar, Shrikant, Brito, Anderson, Fragiadakis, Gabriela K, Patel, Ravi, Overton, James A, Vita, Randi, Westendorf, Kerstin, Shannon, Casey P, Tebbutt, Scott J, Thyagarajan, Rama V, Rousseau, Justin F, Wylie, Dennis, Triplett, Todd A, Kojic, Erna, Chinthrajah, Sharon, Ahuja, Neera, Rogers, Angela J, Artandi, Maja, Geng, Linda, Yendewa, George, Powell, Debra L, Kim, James N, Simmons, Brent, Goonewardene, I Michael, Smith, Cecilia M, Martens, Mark, Sherman, Amy C, Walsh, Stephen R, Issa, Nicolas C, Salehi-Rad, Ramin, Dela Cruz, Charles, Farhadian, Shelli, Iwasaki, Akiko, Ko, Albert I, Anderson, Evan J, Mehta, Aneesh K, and Sevransky, Jonathan E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Coronaviruses, Lung, Emerging Infectious Diseases, Inflammatory and immune system, Good Health and Well Being, Humans, COVID-19, Glycosylation, SARS-CoV-2, Glycosyltransferases, Complement System Proteins, Immunoglobulin M, IMPACC Network
Abstract

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Published
2024

4. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Author

Ozonoff, Al, Jayavelu, Naresh Doni, Liu, Shanshan, Melamed, Esther, Milliren, Carly E., Qi, Jingjing, Geng, Linda N., McComsey, Grace A., Cairns, Charles B., Baden, Lindsey R., Schaenman, Joanna, Shaw, Albert C., Samaha, Hady, Seyfert-Margolis, Vicki, Krammer, Florian, Rosen, Lindsey B., Steen, Hanno, Syphurs, Caitlin, Dandekar, Ravi, Shannon, Casey P., Sekaly, Rafick P., Ehrlich, Lauren I. R., Corry, David B., Kheradmand, Farrah, Atkinson, Mark A., Brakenridge, Scott C., Higuita, Nelson I. Agudelo, Metcalf, Jordan P., Hough, Catherine L., Messer, William B., Pulendran, Bali, Nadeau, Kari C., Davis, Mark M., Sesma, Ana Fernandez, Simon, Viviana, van Bakel, Harm, Kim-Schulze, Seunghee, Hafler, David A., Levy, Ofer, Kraft, Monica, Bime, Chris, Haddad, Elias K., Calfee, Carolyn S., Erle, David J., Langelier, Charles R., Eckalbar, Walter, Bosinger, Steven E., Peters, Bjoern, Kleinstein, Steven H., Reed, Elaine F., Augustine, Alison D., Diray-Arce, Joann, Maecker, Holden T., Altman, Matthew C., Montgomery, Ruth R., Becker, Patrice M., and Rouphael, Nadine

Published
2024
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5. A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

Author

Yin, Qian, Luo, Wei, Mallajosyula, Vamsee, Bo, Yang, Guo, Jing, Xie, Jinghang, Sun, Meng, Verma, Rohit, Li, Chunfeng, Constantz, Christian M, Wagar, Lisa E, Li, Jing, Sola, Elsa, Gupta, Neha, Wang, Chunlin, Kask, Oliver, Chen, Xin, Yuan, Xue, Wu, Nicholas C, Rao, Jianghong, Chien, Yueh-hsiu, Cheng, Jianjun, Pulendran, Bali, and Davis, Mark M

Subjects
Lung, Infectious Diseases, Emerging Infectious Diseases, Pneumonia, Vaccine Related, Biotechnology, Bioengineering, Immunization, Pneumonia & Influenza, Prevention, Biodefense, Influenza, Nanotechnology, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Inflammatory and immune system, Good Health and Well Being, Animals, Mice, Humans, Influenza, Human, Toll-Like Receptor 7, SARS-CoV-2, COVID-19, Influenza Vaccines, Adjuvants, Immunologic, Immunity, Nanoparticles, Vaccines, Subunit, Nanoscience & Nanotechnology
Abstract

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

Published
2023

6. BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance

Author

Lee, Audrey, Floyd, Katharine, Wu, Shengyang, Fang, Zhuoqing, Tan, Tze Kai, Froggatt, Heather M., Powers, John M., Leist, Sarah R., Gully, Kendra L., Hubbard, Miranda L., Li, Chunfeng, Hui, Harold, Scoville, David, Ruggiero, Alistaire D., Liang, Yan, Pavenko, Anna, Lujan, Victor, Baric, Ralph S., Nolan, Garry P., Arunachalam, Prabhu S., Suthar, Mehul S., and Pulendran, Bali

Published
2024
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7. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Ozonoff, Al, Schaenman, Joanna, Jayavelu, Naresh Doni, Milliren, Carly E, Calfee, Carolyn S, Cairns, Charles B, Kraft, Monica, Baden, Lindsey R, Shaw, Albert C, Krammer, Florian, van Bakel, Harm, Esserman, Denise A, Liu, Shanshan, Sesma, Ana Fernandez, Simon, Viviana, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Levy, Ofer, Bime, Christian, Haddad, Elias K, Erle, David J, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, Hough, Catherine L, Messer, William B, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Atkinson, Mark A, Brakenridge, Scott C, Corry, David, Kheradmand, Farrah, Ehrlich, Lauren IR, Melamed, Esther, McComsey, Grace A, Sekaly, Rafick, Diray-Arce, Joann, Peters, Bjoern, Augustine, Alison D, Reed, Elaine F, Altman, Matthew C, Becker, Patrice M, Rouphael, Nadine, Bime, Chris, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Presnell, Scott, and Fragiadakis, Gabriela K

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Emerging Infectious Diseases, Lung, Genetics, Clinical Research, Coronaviruses, Prevention, Good Health and Well Being, COVID-19, Creatinine, Female, Hospitalization, Humans, Male, Phenotype, Prospective Studies, RNA, Viral, SARS-CoV-2, Severity of Illness Index, Troponin, Post-Acute COVID-19 Syndrome, Viral load, Antibody, IMPACC study group members, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.FundingNIH.

Published
2022

8. Acute and persistent responses after H5N1 vaccination in humans

Author

Apps, Richard, Biancotto, Angélique, Candia, Julián, Kotliarov, Yuri, Perl, Shira, Cheung, Foo, Farmer, Rohit, Mulè, Matthew P., Rachmaninoff, Nicholas, Chen, Jinguo, Martins, Andrew J., Shi, Rongye, Zhou, Huizhi, Bansal, Neha, Schum, Paula, Olnes, Matthew J., Milanez-Almeida, Pedro, Han, Kyu Lee, Sellers, Brian, Cortese, Mario, Hagan, Thomas, Rouphael, Nadine, Pulendran, Bali, King, Lisa, Manischewitz, Jody, Khurana, Surender, Golding, Hana, van der Most, Robbert G., Dickler, Howard B., Germain, Ronald N., Schwartzberg, Pamela L., and Tsang, John S.

Published
2024
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10. Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques

Author

Bollimpelli, Venkata S., Reddy, Pradeep B. J, Gangadhara, Sailaja, Charles, Tysheena P., Burton, Samantha L., Tharp, Gregory K., Styles, Tiffany M., Labranche, Celia C., Smith, Justin C., Upadhyay, Amit A., Sahoo, Anusmita, Legere, Traci, Shiferaw, Ayalnesh, Velu, Vijayakumar, Yu, Tianwei, Tomai, Mark, Vasilakos, John, Kasturi, Sudhir P., Shaw, George M., Montefiori, David, Bosinger, Steven E., Kozlowski, Pamela A., Pulendran, Bali, Derdeyn, Cynthia A., Hunter, Eric, and Amara, Rama R.

Published
2023
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11. Author Correction: A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Author

Weidenbacher, Payton A.-B., Sanyal, Mrinmoy, Friedland, Natalia, Tang, Shaogeng, Arunachalam, Prabhu S., Hu, Mengyun, Kumru, Ozan S., Morris, Mary Kate, Fontenot, Jane, Shirreff, Lisa, Do, Jonathan, Cheng, Ya-Chen, Vasudevan, Gayathri, Feinberg, Mark B., Villinger, Francois J., Hanson, Carl, Joshi, Sangeeta B., Volkin, David B., Pulendran, Bali, and Kim, Peter S.

Published
2023
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13. A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Author

Weidenbacher, Payton A.-B., Sanyal, Mrinmoy, Friedland, Natalia, Tang, Shaogeng, Arunachalam, Prabhu S., Hu, Mengyun, Kumru, Ozan S., Morris, Mary Kate, Fontenot, Jane, Shirreff, Lisa, Do, Jonathan, Cheng, Ya-Chen, Vasudevan, Gayathri, Feinberg, Mark B., Villinger, Francois J., Hanson, Carl, Joshi, Sangeeta B., Volkin, David B., Pulendran, Bali, and Kim, Peter S.

Published
2023
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14. Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Author

Chakraborty, Saborni, Gonzalez, Joseph C, Sievers, Benjamin L, Mallajosyula, Vamsee, Chakraborty, Srijoni, Dubey, Megha, Ashraf, Usama, Cheng, Bowie Yik-Ling, Kathale, Nimish, Tran, Kim Quyen Thi, Scallan, Courtney, Sinnott, Aanika, Cassidy, Arianna, Chen, Steven T, Gelbart, Terri, Gao, Fei, Golan, Yarden, Ji, Xuhuai, Kim-Schulze, Seunghee, Prahl, Mary, Gaw, Stephanie L, Gnjatic, Sacha, Marron, Thomas U, Merad, Miriam, Arunachalam, Prabhu S, Boyd, Scott D, Davis, Mark M, Holubar, Marisa, Khosla, Chaitan, Maecker, Holden T, Maldonado, Yvonne, Mellins, Elizabeth D, Nadeau, Kari C, Pulendran, Bali, Singh, Upinder, Subramanian, Aruna, Utz, Paul J, Sherwood, Robert, Zhang, Sheng, Jagannathan, Prasanna, Tan, Gene S, and Wang, Taia T

Subjects
Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Pneumonia & Influenza, Lung, Vaccine Related, Pneumonia, Prevention, Biotechnology, Immunization, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Respiratory, Good Health and Well Being, Antibodies, Neutralizing, Antibodies, Viral, Antibody Formation, COVID-19, COVID-19 Vaccines, Humans, Prospective Studies, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

Published
2022

15. Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

Author

Sievers, Benjamin L, Chakraborty, Saborni, Xue, Yong, Gelbart, Terri, Gonzalez, Joseph C, Cassidy, Arianna G, Golan, Yarden, Prahl, Mary, Gaw, Stephanie L, Arunachalam, Prabhu S, Blish, Catherine A, Boyd, Scott D, Davis, Mark M, Jagannathan, Prasanna, Nadeau, Kari C, Pulendran, Bali, Singh, Upinder, Scheuermann, Richard H, Frieman, Matthew B, Vashee, Sanjay, Wang, Taia T, and Tan, Gene S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Pneumonia, Emerging Infectious Diseases, Biodefense, Pneumonia & Influenza, Prevention, Biotechnology, Vaccine Related, Lung, Clinical Research, Infectious Diseases, Immunization, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adult, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Female, Humans, Pregnancy, Pregnancy Complications, Infectious, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vaccines, Synthetic, mRNA Vaccines, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Published
2022

16. Early immune markers of clinical, virological, and immunological outcomes in patients with COVID-19: a multi-omics study

Author

Hu, Zicheng, van der Ploeg, Kattria, Chakraborty, Saborni, Arunachalam, Prabhu S, Mori, Diego AM, Jacobson, Karen B, Bonilla, Hector, Parsonnet, Julie, Andrews, Jason R, Holubar, Marisa, Subramanian, Aruna, Khosla, Chaitan, Maldonado, Yvonne, Hedlin, Haley, de la Parte, Lauren, Press, Kathleen, Ty, Maureen, Tan, Gene S, Blish, Catherine, Takahashi, Saki, Rodriguez-Barraquer, Isabel, Greenhouse, Bryan, Butte, Atul J, Singh, Upinder, Pulendran, Bali, Wang, Taia T, and Jagannathan, Prasanna

Subjects
Biomedical and Clinical Sciences, Immunology, Immunization, Infectious Diseases, Clinical Research, Emerging Infectious Diseases, Precision Medicine, Machine Learning and Artificial Intelligence, Coronaviruses, Biotechnology, Prevention, Vaccine Related, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Infection, Inflammatory and immune system, Good Health and Well Being, Humans, Antibodies, Viral, Biomarkers, BNT162 Vaccine, COVID-19, Cytokines, Disease Progression, RNA, Messenger, SARS-CoV-2, Clinical Trials as Topic, systems immunology, predictive modeling, Viruses, immunology, inflammation, medicine, viruses, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe great majority of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunological outcomes in SARS-CoV-2-infected patients.MethodsLeveraging longitudinal samples and data from a clinical trial (N=108) in SARS-CoV-2-infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients. We characterized the association between early immune markers and subsequent disease progression, control of viral shedding, and SARS-CoV-2-specific T cell and antibody responses measured up to 7 months after enrollment. We further compared associations between early immune markers and subsequent T cell and antibody responses following natural infection with those following mRNA vaccination. We developed machine-learning models to predict patient outcomes and validated the predictive model using data from 54 individuals enrolled in an independent clinical trial.ResultsWe identify early immune signatures, including plasma RIG-I levels, early IFN signaling, and related cytokines (CXCL10, MCP1, MCP-2, and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2-specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine-learning models using 2-7 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.ConclusionsEarly immune signatures following infection can accurately predict clinical and immunological outcomes in outpatients with COVID-19 using validated machine-learning models.FundingSupport for the study was provided from National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) (U01 AI150741-01S1 and T32-AI052073), the Stanford's Innovative Medicines Accelerator, National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA) DP1DA046089, and anonymous donors to Stanford University. Peginterferon lambda provided by Eiger BioPharmaceuticals.

Published
2022

18. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study

Author

Rouphael, Nadine, Maecker, Holden, Montgomery, Ruth R, Diray-Arce, Joann, Kleinstein, Steven H, Altman, Matthew C, Bosinger, Steven E, Eckalbar, Walter, Guan, Leying, Hough, Catherine L, Krammer, Florian, Langelier, Charles, Levy, Ofer, McEnaney, Kerry, Peters, Bjoern, Rahman, Adeeb, Rajan, Jayant V, Sigelman, Steven, Steen, Hanno, van Bakel, Harm, Ward, Alyssa, Wilson, Michael R, Woodruff, Prescott, Zamecnik, Colin R, Augustine, Alison D, Ozonoff, Al, Reed, Elaine F, Becker, Patrice M, Higuita, Nelson Agudelo, Atkinson, Mark A, Baden, Lindsey R, Bime, Christian, Brakenridge, Scott C, Calfee, Carolyn S, Cairns, Charles B, Corry, David, Davis, Mark M, Ehrlich, Lauren IR, Haddad, Elias K, Erle, David J, Fernandez-Sesma, Ana, Hafler, David A, Kheradmand, Farrah, Kraft, Monica, McComsey, Grace A, Melamed, Esther, Messer, William, Metcalf, Jordan, Nadeau, Kari C, Pulendran, Bali, Sarwal, Minnie, Schaenman, Joanna, Sekaly, Rafick, Shaw, Albert C, and Simon, Viviana

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Biomarkers, COVID-19, Computational Biology, Data Analysis, Gene Expression Profiling, Hospitalization, Humans, Immunophenotyping, Longitudinal Studies, Molecular Diagnostic Techniques, Prospective Studies, Proteomics, SARS-CoV-2, United States, IMPACC Manuscript Writing Team, IMPACC Network Steering Committee, Clinical sciences, Immunology
Abstract

The IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective longitudinal study designed to enroll 1000 hospitalized patients with COVID-19 (NCT04378777). IMPACC collects detailed clinical, laboratory and radiographic data along with longitudinal biologic sampling of blood and respiratory secretions for in depth testing. Clinical and lab data are integrated to identify immunologic, virologic, proteomic, metabolomic and genomic features of COVID-19-related susceptibility, severity and disease progression. The goals of IMPACC are to better understand the contributions of pathogen dynamics and host immune responses to the severity and course of COVID-19 and to generate hypotheses for identification of biomarkers and effective therapeutics, including optimal timing of such interventions. In this report we summarize the IMPACC study design and protocols including clinical criteria and recruitment, multi-site standardized sample collection and processing, virologic and immunologic assays, harmonization of assay protocols, high-level analyses and the data sharing plans.

Published
2021

19. Systems view of Bordetella pertussis booster vaccination in adults primed with whole-cell vs. acellular vaccine

Author

da Silva Antunes, Ricardo, Soldevila, Ferran, Pomaznoy, Mikhail, Babor, Mariana, Bennett, Jason, Tian, Yuan, Khalil, Natalie N, Qian, Yu, Mandava, Aishwarya, Scheuermann, Richard H, Cortese, Mario, Pulendran, Bali, Petro, Christopher D, Gilkes, Adrienne P, Purcell, Lisa A, Sette, Alessandro, and Peters, Bjoern

Subjects
Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Vaccine Related, Immunization, Biodefense, Prevention, Emerging Infectious Diseases, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Inflammatory and immune system, Good Health and Well Being, Antibodies, Bacterial, Bordetella pertussis, Chemokine CCL3, Cytokines, Gene Expression, Humans, Immunity, Humoral, Immunization, Secondary, Intercellular Adhesion Molecule-1, NF-KappaB Inhibitor alpha, Neutrophils, Pertussis Vaccine, Vaccines, Acellular, Bacterial vaccines, Imprinting, Vaccines, Biomedical and clinical sciences, Health sciences
Abstract

The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show that, while broad immune response patterns to Tdap boost overlap between aP- and wP-primed individuals, a subset of aP-primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

Published
2021

20. Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth

Author

Wimmers, Florian, Burrell, Allison R., Feng, Yupeng, Zheng, Hong, Arunachalam, Prabhu S., Hu, Mengyun, Spranger, Sara, Nyhoff, Lindsay E., Joshi, Devyani, Trisal, Meera, Awasthi, Mayanka, Bellusci, Lorenza, Ashraf, Usama, Kowli, Sangeeta, Konvinse, Katherine C., Yang, Emily, Blanco, Michael, Pellegrini, Kathryn, Tharp, Gregory, Hagan, Thomas, Chinthrajah, R. Sharon, Nguyen, Tran T., Grifoni, Alba, Sette, Alessandro, Nadeau, Kari C., Haslam, David B., Bosinger, Steven E., Wrammert, Jens, Maecker, Holden T., Utz, Paul J., Wang, Taia T., Khurana, Surender, Khatri, Purvesh, Staat, Mary A., and Pulendran, Bali

Published
2023
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21. SREBP signaling is essential for effective B cell responses

Author

Luo, Wei, Adamska, Julia Z., Li, Chunfeng, Verma, Rohit, Liu, Qing, Hagan, Thomas, Wimmers, Florian, Gupta, Shakti, Feng, Yupeng, Jiang, Wenxia, Zhou, Jiehao, Valore, Erika, Wang, Yanli, Trisal, Meera, Subramaniam, Shankar, Osborne, Timothy F., and Pulendran, Bali

Published
2023
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22. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses

Author

Hagan, Thomas, Gerritsen, Bram, Tomalin, Lewis E., Fourati, Slim, Mulè, Matthew P., Chawla, Daniel G., Rychkov, Dmitri, Henrich, Evan, Miller, Helen E. R., Diray-Arce, Joann, Dunn, Patrick, Lee, Audrey, Levy, Ofer, Gottardo, Raphael, Sarwal, Minne M., Tsang, John S., Suárez-Fariñas, Mayte, Sékaly, Rafick-Pierre, Kleinstein, Steven H., and Pulendran, Bali

Published
2022
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23. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination

Author

Fourati, Slim, Tomalin, Lewis E., Mulè, Matthew P., Chawla, Daniel G., Gerritsen, Bram, Rychkov, Dmitry, Henrich, Evan, Miller, Helen E. R., Hagan, Thomas, Diray-Arce, Joann, Dunn, Patrick, Levy, Ofer, Gottardo, Raphael, Sarwal, Minnie M., Tsang, John S., Suárez-Fariñas, Mayte, Pulendran, Bali, Kleinstein, Steven H., and Sékaly, Rafick-Pierre

Published
2022
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25. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano, Luz Torres, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Christian, Boddapati, Arun Kumar, Booth, J. Leland, Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño, Juan Manuel, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, Bermúdez González, Maria Carolina, Goonewardene, I. Michael, Guerrero, Estella Sanchez, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati, Arash Nemati, Hendrickson, Carolyn M., Agudelo Higuita, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele A., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning, Brittany Roth, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid, Ahmad Sadeed, Raskin, Ariel, Reed, Elaine F., Ribeiro, Susan Pereira, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Published
2023
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26. Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection

Author

Gao, Fei, Mallajoysula, Vamsee, Arunachalam, Prabhu S., van der Ploeg, Kattria, Manohar, Monali, Röltgen, Katharina, Yang, Fan, Wirz, Oliver, Hoh, Ramona, Haraguchi, Emily, Lee, Ji-Yeun, Willis, Richard, Ramachandiran, Vasanthi, Li, Jiefu, Kathuria, Karan Raj, Li, Chunfeng, Lee, Alexandra S., Shah, Mihir M., Sindher, Sayantani B., Gonzalez, Joseph, Altman, John D., Wang, Taia T., Boyd, Scott D., Pulendran, Bali, Jagannathan, Prasanna, Nadeau, Kari C., and Davis, Mark.M.

Published
2023
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28. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine

Author

Li, Chunfeng, Lee, Audrey, Grigoryan, Lilit, Arunachalam, Prabhu S., Scott, Madeleine K. D., Trisal, Meera, Wimmers, Florian, Sanyal, Mrinmoy, Weidenbacher, Payton A., Feng, Yupeng, Adamska, Julia Z., Valore, Erika, Wang, Yanli, Verma, Rohit, Reis, Noah, Dunham, Diane, O’Hara, Ruth, Park, Helen, Luo, Wei, Gitlin, Alexander D., Kim, Peter, Khatri, Purvesh, Nadeau, Kari C., and Pulendran, Bali

Published
2022
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30. The Immune Signatures data resource, a compendium of systems vaccinology datasets

Author

Diray-Arce, Joann, Miller, Helen E. R., Henrich, Evan, Gerritsen, Bram, Mulè, Matthew P., Fourati, Slim, Gygi, Jeremy, Hagan, Thomas, Tomalin, Lewis, Rychkov, Dmitry, Kazmin, Dmitri, Chawla, Daniel G., Meng, Hailong, Dunn, Patrick, Campbell, John, Sarwal, Minnie, Tsang, John S., Levy, Ofer, Pulendran, Bali, Sekaly, Rafick, Floratos, Aris, Gottardo, Raphael, Kleinstein, Steven H., and Suárez-Fariñas, Mayte

Published
2022
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32. Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice

Author

Grigoryan, Lilit, Lee, Audrey, Walls, Alexandra C., Lai, Lilin, Franco, Benjamin, Arunachalam, Prabhu S., Feng, Yupeng, Luo, Wei, Vanderheiden, Abigail, Floyd, Katharine, Wrenn, Samuel, Pettie, Deleah, Miranda, Marcos C., Kepl, Elizabeth, Ravichandran, Rashmi, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, Coffman, Robert L., Novack, David, Kleanthous, Harry, O’Hagan, Derek T., van der Most, Robbert, McLellan, Jason S., Suthar, Mehul, Veesler, David, King, Neil P., and Pulendran, Bali

Published
2022
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33. Elucidating allergic reaction mechanisms in response to SARS‐CoV‐2 mRNA vaccination in adults.

Author

Shah, Mihir M., Layhadi, Janice A., Hourcade, Dennis E., Fulton, William T., Tan, Tiak Ju, Dunham, Diane, Chang, Iris, Vel, Monica S., Fernandes, Andrea, Lee, Alexandra S., Liu, James, Arunachalam, Prabhu S., Galli, Stephen J., Boyd, Scott D., Pulendran, Bali, Davis, Mark M., O'Hara, Ruth, Park, Helen, Mitchell, Lynne M., and Akk, Antonina

Subjects
MACROPHAGES, VACCINE hesitancy, COMPLEMENT activation, POLYETHYLENE glycol, ALLERGIES
Abstract

Background: During the COVID‐19 pandemic, novel nanoparticle‐based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. Methods: To understand COVID‐19 vaccine‐mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. Results: Vaccine‐mediated complement activation correlated with anti‐polyethelyne glycol (PEG) IgG (but not IgM) levels while anti‐PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine‐mediated basophil activation. Single‐cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll‐like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL‐13 and IL‐1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. Conclusion: These findings provide insights into the mechanisms underlying allergic reactions to COVID‐19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Author Correction: Systems vaccinology of the BNT162b2 mRNA vaccine in humans

Author

Arunachalam, Prabhu S., Scott, Madeleine K. D., Hagan, Thomas, Li, Chunfeng, Feng, Yupeng, Wimmers, Florian, Grigoryan, Lilit, Trisal, Meera, Edara, Venkata Viswanadh, Lai, Lilin, Chang, Sarah Esther, Feng, Allan, Dhingra, Shaurya, Shah, Mihir, Lee, Alexandra S., Chinthrajah, Sharon, Sindher, Sayantani B., Mallajosyula, Vamsee, Gao, Fei, Sigal, Natalia, Kowli, Sangeeta, Gupta, Sheena, Pellegrini, Kathryn, Tharp, Gregory, Maysel-Auslender, Sofia, Hamilton, Sydney, Aoued, Hadj, Hrusovsky, Kevin, Roskey, Mark, Bosinger, Steven E., Maecker, Holden T., Boyd, Scott D., Davis, Mark M., Utz, Paul J., Suthar, Mehul S., Khatri, Purvesh, Nadeau, Kari C., and Pulendran, Bali

Published
2023
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36. Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates

Author

Pillet, Stéphane, Arunachalam, Prabhu S., Andreani, Guadalupe, Golden, Nadia, Fontenot, Jane, Aye, Pyone Pyone, Röltgen, Katharina, Lehmicke, Gabrielle, Gobeil, Philipe, Dubé, Charlotte, Trépanier, Sonia, Charland, Nathalie, D’Aoust, Marc-André, Russell-Lodrigue, Kasi, Monjure, Christopher, Blair, Robert V., Boyd, Scott D., Bohm, Rudolf P., Rappaport, Jay, Villinger, François, Landry, Nathalie, Pulendran, Bali, and Ward, Brian J.

Published
2022
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38. Cell type discovery and representation in the era of high-content single cell phenotyping

Author

Bakken, Trygve, Cowell, Lindsay, Aevermann, Brian D, Novotny, Mark, Hodge, Rebecca, Miller, Jeremy A, Lee, Alexandra, Chang, Ivan, McCorrison, Jamison, Pulendran, Bali, Qian, Yu, Schork, Nicholas J, Lasken, Roger S, Lein, Ed S, and Scheuermann, Richard H

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Networking and Information Technology R&D (NITRD), Genetics, Biotechnology, Biological Ontologies, Biomarkers, Cells, Computational Biology, Humans, Sequence Analysis, RNA, Single-Cell Analysis, Cell ontology, Single cell transcriptomics, Cell phenotype, Peripheral blood mononuclear cells, Neuron, Next generation sequencing, Cytometry, Open biomedical ontologies, Marker genes, Mathematical Sciences, Information and Computing Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

BackgroundA fundamental characteristic of multicellular organisms is the specialization of functional cell types through the process of differentiation. These specialized cell types not only characterize the normal functioning of different organs and tissues, they can also be used as cellular biomarkers of a variety of different disease states and therapeutic/vaccine responses. In order to serve as a reference for cell type representation, the Cell Ontology has been developed to provide a standard nomenclature of defined cell types for comparative analysis and biomarker discovery. Historically, these cell types have been defined based on unique cellular shapes and structures, anatomic locations, and marker protein expression. However, we are now experiencing a revolution in cellular characterization resulting from the application of new high-throughput, high-content cytometry and sequencing technologies. The resulting explosion in the number of distinct cell types being identified is challenging the current paradigm for cell type definition in the Cell Ontology.ResultsIn this paper, we provide examples of state-of-the-art cellular biomarker characterization using high-content cytometry and single cell RNA sequencing, and present strategies for standardized cell type representations based on the data outputs from these cutting-edge technologies, including "context annotations" in the form of standardized experiment metadata about the specimen source analyzed and marker genes that serve as the most useful features in machine learning-based cell type classification models. We also propose a statistical strategy for comparing new experiment data to these standardized cell type representations.ConclusionThe advent of high-throughput/high-content single cell technologies is leading to an explosion in the number of distinct cell types being identified. It will be critical for the bioinformatics community to develop and adopt data standard conventions that will be compatible with these new technologies and support the data representation needs of the research community. The proposals enumerated here will serve as a useful starting point to address these challenges.

Published
2017

39. Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

Author

Sarin, Kavita Y., primary, Zheng, Hong, additional, Chaichian, Yashaar, additional, Arunachalam, Prabhu S., additional, Swaminathan, Gayathri, additional, Eschholz, Alec, additional, Gao, Fei, additional, Wirz, Oliver F., additional, Lam, Brandon, additional, Yang, Emily, additional, Lee, Lori W., additional, Feng, Allan, additional, Lewis, Matthew A., additional, Lin, Janice, additional, Maecker, Holden T., additional, Boyd, Scott D., additional, Davis, Mark M., additional, Nadeau, Kari C., additional, Pulendran, Bali, additional, Khatri, Purvesh, additional, Utz, Paul J., additional, and Zaba, Lisa C., additional

Published
2024
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40. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines

Author

Walls, Alexandra C., Miranda, Marcos C., Schäfer, Alexandra, Pham, Minh N., Greaney, Allison, Arunachalam, Prabhu S., Navarro, Mary-Jane, Tortorici, M. Alejandra, Rogers, Kenneth, O’Connor, Megan A., Shirreff, Lisa, Ferrell, Douglas E., Bowen, John, Brunette, Natalie, Kepl, Elizabeth, Zepeda, Samantha K., Starr, Tyler, Hsieh, Ching-Lin, Fiala, Brooke, Wrenn, Samuel, Pettie, Deleah, Sydeman, Claire, Sprouse, Kaitlin R., Johnson, Max, Blackstone, Alyssa, Ravichandran, Rashmi, Ogohara, Cassandra, Carter, Lauren, Tilles, Sasha W., Rappuoli, Rino, Leist, Sarah R., Martinez, David R., Clark, Matthew, Tisch, Roland, O’Hagan, Derek T., Van Der Most, Robbert, Van Voorhis, Wesley C., Corti, Davide, McLellan, Jason S., Kleanthous, Harry, Sheahan, Timothy P., Smith, Kelly D., Fuller, Deborah H., Villinger, Francois, Bloom, Jesse, Pulendran, Bali, Baric, Ralph S., King, Neil P., and Veesler, David

Published
2021
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41. Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans

Author

Ellebedy, Ali H., Nachbagauer, Raffael, Jackson, Katherine J. L., Dai, Ya-Nan, Han, Julianna, Alsoussi, Wafaa B., Davis, Carl W., Stadlbauer, Daniel, Rouphael, Nadine, Chromikova, Veronika, McCausland, Megan, Chang, Cathy Y., Cortese, Mario, Bower, Mary, Chennareddy, Chakravarthy, Schmitz, Aaron J., Zarnitsyna, Veronika I., Lai, Lilin, Rajabhathor, Arvind, Kazemian, Cheyann, Antia, Rustom, Mulligan, Mark J., Ward, Andrew B., Fremont, Daved H., Boyd, Scott D., Pulendran, Bali, Krammer, Florian, and Ahmed, Rafi

Published
2020

42. Durability of immune responses to mRNA booster vaccination against COVID-19

Author

Arunachalam, Prabhu S., Lai, Lilin, Samaha, Hady, Feng, Yupeng, Hu, Mengyun, Hui, Harold Sai-yin, Wali, Bushra, Ellis, Madison, Davis-Gardner, Meredith E., Huerta, Christopher, Bechnak, Kareem, Bechnak, Sarah, Lee, Matthew, Litvack, Matthew B., Losada, Cecilia, Grifoni, Alba, Sette, Alessandro, Zarnitsyna, Veronika I., Rouphael, Nadine, Suthar, Mehul S., and Pulendran, Bali

Subjects
Immune response -- Health aspects -- Physiological aspects, Health care industry, Comirnaty (Vaccine) -- Physiological aspects -- Comparative analysis, Spikevax (Vaccine) -- Comparative analysis -- Physiological aspects
Abstract

BACKGROUND. Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown. METHODS. We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses. RESULTS. The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. CONCLUSION. The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines., Introduction Recent studies have shown the declining efficacy of the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273) mRNA vaccines after primary and booster vaccinations (1, 2). Although the booster vaccination (third dose) [...]

Published
2023
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43. The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination

Author

Wimmers, Florian, Donato, Michele, Kuo, Alex, Ashuach, Tal, Gupta, Shakti, Li, Chunfeng, Dvorak, Mai, Foecke, Mariko Hinton, Chang, Sarah E., Hagan, Thomas, De Jong, Sanne E., Maecker, Holden T., van der Most, Robbert, Cheung, Peggie, Cortese, Mario, Bosinger, Steven E., Davis, Mark, Rouphael, Nadine, Subramaniam, Shankar, Yosef, Nir, Utz, Paul J., Khatri, Purvesh, and Pulendran, Bali

Published
2021
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44. Systems vaccinology of the BNT162b2 mRNA vaccine in humans

Author

Arunachalam, Prabhu S., Scott, Madeleine K. D., Hagan, Thomas, Li, Chunfeng, Feng, Yupeng, Wimmers, Florian, Grigoryan, Lilit, Trisal, Meera, Edara, Venkata Viswanadh, Lai, Lilin, Chang, Sarah Esther, Feng, Allan, Dhingra, Shaurya, Shah, Mihir, Lee, Alexandra S., Chinthrajah, Sharon, Sindher, Sayantani B., Mallajosyula, Vamsee, Gao, Fei, Sigal, Natalia, Kowli, Sangeeta, Gupta, Sheena, Pellegrini, Kathryn, Tharp, Gregory, Maysel-Auslender, Sofia, Hamilton, Sydney, Aoued, Hadj, Hrusovsky, Kevin, Roskey, Mark, Bosinger, Steven E., Maecker, Holden T., Boyd, Scott D., Davis, Mark M., Utz, Paul J., Suthar, Mehul S., Khatri, Purvesh, Nadeau, Kari C., and Pulendran, Bali

Published
2021
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45. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Author

Arunachalam, Prabhu S., Walls, Alexandra C., Golden, Nadia, Atyeo, Caroline, Fischinger, Stephanie, Li, Chunfeng, Aye, Pyone, Navarro, Mary Jane, Lai, Lilin, Edara, Venkata Viswanadh, Röltgen, Katharina, Rogers, Kenneth, Shirreff, Lisa, Ferrell, Douglas E., Wrenn, Samuel, Pettie, Deleah, Kraft, John C., Miranda, Marcos C., Kepl, Elizabeth, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, White, Alexander G., Trisal, Meera, Hsieh, Ching-Lin, Russell-Lodrigue, Kasi, Monjure, Christopher, Dufour, Jason, Spencer, Skye, Doyle-Meyers, Lara, Bohm, Rudolph P., Maness, Nicholas J., Roy, Chad, Plante, Jessica A., Plante, Kenneth S., Zhu, Alex, Gorman, Matthew J., Shin, Sally, Shen, Xiaoying, Fontenot, Jane, Gupta, Shakti, O’Hagan, Derek T., Van Der Most, Robbert, Rappuoli, Rino, Coffman, Robert L., Novack, David, McLellan, Jason S., Subramaniam, Shankar, Montefiori, David, Boyd, Scott D., Flynn, JoAnne L., Alter, Galit, Villinger, Francois, Kleanthous, Harry, Rappaport, Jay, Suthar, Mehul S., King, Neil P., Veesler, David, and Pulendran, Bali

Published
2021
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47. Single cell multi-omic analysis identifies key genes differentially expressed in innate lymphoid cells from COVID-19 patients.

Author

Kaushik, Abhinav, Chang, Iris, Xiaorui Han, Ziyuan He, Komlosi, Zsolt I., Xuhuai Ji, Shu Cao, Akdis, Cezmi A., Boyd, Scott, Pulendran, Bali, Maecker, Holden T., Davis, Mark M., Chinthrajah, R. Sharon, DeKruyff, Rosemarie H., and Nadeau, Kari C.

Subjects
INNATE lymphoid cells, COVID-19, COVID-19 pandemic, CELL analysis, GENE regulatory networks
Abstract

Introduction: Innate lymphoid cells (ILCs) are enriched at mucosal surfaces where they respond rapidly to environmental stimuli and contribute to both tissue inflammation and healing. Methods: To gain insight into the role of ILCs in the pathology and recovery from COVID-19 infection, we employed a multi-omics approach consisting of Abseq and targeted mRNA sequencing to respectively probe the surface marker expression, transcriptional profile and heterogeneity of ILCs in peripheral blood of patients with COVID-19 compared with healthy controls. Results: We found that the frequency of ILC1 and ILC2 cells was significantly increased in COVID-19 patients. Moreover, all ILC subsets displayed a significantly higher frequency of CD69-expressing cells, indicating a heightened state of activation. ILC2s from COVID-19 patients had the highest number of significantly differentially expressed (DE) genes. The most notable genes DE in COVID-19 vs healthy participants included a) genes associated with responses to virus infections and b) genes that support ILC self-proliferation, activation and homeostasis. In addition, differential gene regulatory network analysis revealed ILC-specific regulons and their interactions driving the differential gene expression in each ILC. Discussion: Overall, this study provides mechanistic insights into the characteristics of ILC subsets activated during COVID-19 infection. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques

Author

Iyer, Smita S, Gangadhara, Sailaja, Victor, Blandine, Shen, Xiaoying, Chen, Xuemin, Nabi, Rafiq, Kasturi, Sudhir P, Sabula, Michael J, Labranche, Celia C, Reddy, Pradeep BJ, Tomaras, Georgia D, Montefiori, David C, Moss, Bernard, Spearman, Paul, Pulendran, Bali, Kozlowski, Pamela A, and Amara, Rama Rao

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Immunization, Vaccine Related, Infectious Diseases, HIV/AIDS, Vaccine Related (AIDS), Prevention, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, Animals, Antibodies, Viral, Antibody Formation, Drug Carriers, Macaca mulatta, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Treatment Outcome, Vaccines, DNA, Vaccines, Synthetic, Vaccines, Virus-Like Particle, Vaccinia virus, Viral Envelope Proteins, Viremia, Simian immunodeficiency virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

UnlabelledThe encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immunity is critically determined by HIV envelope (Env) conformation, significant efforts are directed toward generating soluble trimeric Env immunogens that assume native structures. Using the simian immunodeficiency virus (SIV)-macaque model, we tested the immunogenicity and efficacy of sequential immunizations with DNA (D), modified vaccinia virus Ankara (MVA) (M), and protein immunogens, all expressing virus-like particles (VLPs) displaying membrane-anchored trimeric Env. A single VLP protein boost displaying trimeric gp160 adjuvanted with nanoparticle-encapsulated Toll-like receptor 4/7/8 (TLR4/7/8) agonists, administered 44 weeks after the second MVA immunization, induced up to a 3-fold increase in Env-specific IgG binding titers in serum and mucosa. Importantly, the VLP protein boost increased binding antibody against scaffolded V1V2, antibody-dependent phagocytic activity against VLP-coated beads, and antibody breadth and neutralizing antibody titers against homologous and heterologous tier 1 SIVs. Following 5 weekly intrarectal SIVmac251 challenges, two of seven DNA/MVA and VLP (DM+VLP)-vaccinated animals were completely protected compared to productive infection in all seven DM-vaccinated animals. Vaccinated animals demonstrated stronger acute viral pulldown than controls, but a trend for higher acute viremia was observed in the DM+VLP group, likely due to a slower recall of Gag-specific CD8 T cells. Our findings support immunization with VLPs containing trimeric Env as a strategy to augment protective antibody but underscore the need for optimal engagement of CD8 T cells to achieve robust early viral control.ImportanceThe development of an effective HIV vaccine remains a global necessity for preventing HIV infection and reducing the burden of AIDS. While this goal represents a formidable challenge, the modest efficacy of the RV144 trial indicates that multicomponent vaccination regimens that elicit both cellular and humoral immune responses can prevent HIV infection in humans. However, whether protein immunizations synergize with DNA prime-viral vector boosts to enhance cellular and humoral immune responses remains poorly understood. We addressed this question in a nonhuman primate model, and our findings show benefit for sequential protein immunization combined with a potent adjuvant in boosting antibody titers induced by a preceding DNA/MVA immunization. This promising strategy can be further developed to enhance neutralizing antibody responses and boost CD8 T cells to provide robust protection and viral control.

Published
2016

50. Corrigendum to “Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study” [eBioMedicine 83 (2022) 104208]

Author

Ozonoff, Al, primary, Schaenman, Joanna, additional, Jayavelu, Naresh Doni, additional, Milliren, Carly E., additional, Calfee, Carolyn S., additional, Cairns, Charles B., additional, Kraft, Monica, additional, Baden, Lindsey R., additional, Shaw, Albert C., additional, Krammer, Florian, additional, van Bakel, Harm, additional, Esserman, Denise A., additional, Liu, Shanshan, additional, Sesma, Ana Fernandez, additional, Simon, Viviana, additional, Hafler, David A., additional, Montgomery, Ruth R., additional, Kleinstein, Steven H., additional, Levy, Ofer, additional, Bime, Chris, additional, Haddad, Elias K., additional, Erle, David J., additional, Pulendran, Bali, additional, Nadeau, Kari C., additional, Davis, Mark M., additional, Hough, Catherine L., additional, Messer, William B., additional, Agudelo Higuita, Nelson I., additional, Metcalf, Jordan P., additional, Atkinson, Mark A., additional, Brakenridge, Scott C., additional, Corry, David, additional, Kheradmand, Farrah, additional, Ehrlich, Lauren I.R., additional, Melamed, Esther, additional, McComsey, Grace A., additional, Sekaly, Rafick, additional, Diray-Arce, Joann, additional, Peters, Bjoern, additional, Augustine, Alison D., additional, Reed, Elaine F., additional, Altman, Matthew C., additional, Becker, Patrice M., additional, and Rouphael, Nadine, additional

Published
2023
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