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2. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

Author

Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B. H., Lau, Jillian S. Y., Copertino, Jr, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, and Søgaard, Ole S.

Published
2023
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3. Epigenetic landscape in the kick-and-kill therapeutic vaccine BCN02 clinical trial is associated with antiretroviral treatment interruption (ATI) outcome

Author

Oriol-Tordera, Bruna, Esteve-Codina, Anna, Berdasco, María, Rosás-Umbert, Míriam, Gonçalves, Elena, Duran-Castells, Clara, Català-Moll, Francesc, Llano, Anuska, Cedeño, Samandhy, Puertas, Maria C, Tolstrup, Martin, Søgaard, Ole S, Clotet, Bonaventura, Martínez-Picado, Javier, Hanke, Tomáš, Combadiere, Behazine, Paredes, Roger, Hartigan-O'Connor, Dennis, Esteller, Manel, Meulbroek, Michael, Calle, María Luz, Sanchez-Pla, Alex, Moltó, José, Mothe, Beatriz, Brander, Christian, and Ruiz-Riol, Marta

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Human Genome, Genetics, Vaccine Related, HIV/AIDS, Sexually Transmitted Infections, Immunization, Infection, Good Health and Well Being, Anti-Retroviral Agents, CD4-Positive T-Lymphocytes, Chromatin, Epigenesis, Genetic, HIV Infections, Humans, Leukocytes, Mononuclear, Proviruses, Vaccines, Viral Load, HIV-1 vaccine, Epigenetics, DNA methylation, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundThe BCN02-trial combined therapeutic vaccination with a viral latency reversing agent (romidepsin, RMD) in HIV-1-infected individuals and included a monitored antiretroviral pause (MAP) as an efficacy read-out identifying individuals with an early or late (< or > 4weeks) viral-rebound. Integrated -omics analyses were applied prior treatment interruption to identify markers of virus control during MAP.MethodsPBMC, whole-genome DNA methylation and transcriptomics were assessed in 14 BCN02 participants, including 8 Early and 4 Late viral-rebound individuals. Chromatin state, histone marks and integration analysis (histone-3 acetylation (H3Ac), viral load, proviral levels and HIV-specific T cells responses) were included. REDUC-trial samples (n = 5) were included as a control group for RMD administration alone.FindingsDNA methylation imprints after receiving the complete intervention discriminated Early versus Late viral-rebound individuals before MAP. Also, differential chromatin accessibility and histone marks at DNA methylation level were detected. Importantly, the differential DNA methylation positions (DMPs) between Early and Late rebounders before MAP were strongly associated with viral load, proviral levels as well as the HIV-specific T-cell responses. Most of these DMPs were already present prior to the intervention and accentuated after RMD infusion.InterpretationThis study identifies host DNA methylation profiles and epigenetic cascades that are predictive of subsequent virus control in a kick-and-kill HIV cure strategy.FundingEuropean Union Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement N°681137-EAVI2020 and N°847943-MISTRAL, the Ministerio de Ciencia e Innovación (SAF2017_89726_R), and the National Institutes of Health-National Institute of Allergy and Infectious Diseases Program Grant P01-AI131568.

Published
2022

6. SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection

Author

Lundgren, J., Østergaard, L., Benfield, T., Krohn-Dehli, L., Petersen, D.K., Fogh, K., Højmark, E., Iversen, K.K., Bek, P., Klastrup, V., Larsen, F., Rasmussen, S.H., Schleimann, M.H., Schieber, S., Stærke, N.B., Søndergaard, A., Tarp, B., Tousgaard, M., Yehdego, Y., Bodilsen, J., Nielsen, H., Petersen, K.T., Ruwald, M., Thisted, R.K., Caspersen, S.F., Iversen, M., Knudsen, L.S., Meyerhoff, J.L., Sander, L.G., Wiese, L., Abildgaard, C., Holden, I.K., Johansen, N.E., Johansen, I.S., Larsen, L., Lindvig, S.O., Madsen, L.W., Øvrehus, A., Kruse, N.A., Lomholdt, H., Krause, T.G., Valentiner-Branth, P., Søborg, B., Fischer, T.K., Erikstrup, C., Ostrowski, S.R., Tolstrup, M., Søgaard, O.S., Raben, D., Jylling, E., Hougaard, D., Andersen, S.D., Lykkegaard, K., Andreasen, S.R., Baerends, E., Dietz, L.L., Hvidt, A.K., Juhl, A.K., Olesen, R., Andersen, K.K., Bannister, W., Bjernved, C., Elsing, T.W., Esmann, F.V., Ghafari, M.A., Gravholdt, E., Jakobsen, S.F., Jakobsen, M.L., Jensen, C.M., Jensen, T.Ø., Kristensen, D., Kumar, L.R., Matthews, C., Normand, N., Olsson, C., Reekie, J., Traytel, A., Weide, T., Hvas, A.M., Støvring, H., Baerends, Eva A.M., Hvidt, Astrid K., Reekie, Joanne, Søgaard, Ole S., Stærke, Nina B., Raben, Dorthe, Nielsen, Henrik, Petersen, Kristine T., Juhl, Maria R., Johansen, Isik S., Lindvig, Susan O., Madsen, Lone W., Wiese, Lothar, Knudsen, Lene S., Iversen, Mette B., Benfield, Thomas, Iversen, Kasper K., Andersen, Sidsel D., Juhl, Anna K., Dietz, Lisa L., Andreasen, Signe R., Fischer, Thea K., Erikstrup, Christian, Valentiner-Branth, Palle, Lundgren, Jens, Østergaard, Lars, and Tolstrup, Martin

Published
2023
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8. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial

Author

Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I-Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D. Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, and Søgaard, Ole S.

Published
2022
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9. Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption

Author

Vibholm, Line K, Lorenzi, Julio CC, Pai, Joy A, Cohen, Yehuda Z, Oliveira, Thiago Y, Barton, John P, Noceda, Marco Garcia, Lu, Ching-Lan, Ablanedo-Terrazas, Yuria, Del Rio Estrada, Perla M, Reyes-Teran, Gustavo, Tolstrup, Martin, Denton, Paul W, Damsgaard, Tine, Søgaard, Ole S, and Nussenzweig, Michel C

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Adult, Anti-Retroviral Agents, CD4-Positive T-Lymphocytes, DNA, Viral, Female, HIV Infections, HIV-1, Humans, Lymph Nodes, Male, Middle Aged, Proviruses, Toll-Like Receptor 9, ATI, infectious diseases, recombination, lymph node, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination.

Published
2019

10. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting

Author

Julg, Boris, Dee, Lynda, Ananworanich, Jintanat, Barouch, Dan H, Bar, Katharine, Caskey, Marina, Colby, Donn J, Dawson, Liza, Dong, Krista L, Dubé, Karine, Eron, Joseph, Frater, John, Gandhi, Rajesh T, Geleziunas, Romas, Goulder, Philip, Hanna, George J, Jefferys, Richard, Johnston, Rowena, Kuritzkes, Daniel, Li, Jonathan Z, Likhitwonnawut, Udom, van Lunzen, Jan, Martinez-Picado, Javier, Miller, Veronica, Montaner, Luis J, Nixon, Douglas F, Palm, David, Pantaleo, Giuseppe, Peay, Holly, Persaud, Deborah, Salzwedel, Jessica, Salzwedel, Karl, Schacker, Timothy, Sheikh, Virginia, Søgaard, Ole S, Spudich, Serena, Stephenson, Kathryn, Sugarman, Jeremy, Taylor, Jeff, Tebas, Pablo, Tiemessen, Caroline T, Tressler, Randall, Weiss, Carol D, Zheng, Lu, Robb, Merlin L, Michael, Nelson L, Mellors, John W, Deeks, Steven G, and Walker, Bruce D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, Clinical Trials and Supportive Activities, HIV/AIDS, Clinical Research, 6.1 Pharmaceuticals, 6.9 Resources and infrastructure (treatment evaluation), Infection, Anti-Retroviral Agents, HIV Infections, Humans, Sustained Virologic Response, Viral Load, Withholding Treatment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

Published
2019

11. Characterization of the HIV-1 transcription profile after romidepsin administration in ART-suppressed individuals

Author

Moron-Lopez, Sara, Kim, Peggy, Søgaard, Ole S, Tolstrup, Martin, Wong, Joseph K, and Yukl, Steven A

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Genetics, Sexually Transmitted Infections, HIV/AIDS, Infection, Anti-Retroviral Agents, Antibiotics, Antineoplastic, Depsipeptides, Follow-Up Studies, Gene Expression Profiling, HIV Infections, HIV-1, Humans, Sustained Virologic Response, Transcription, Genetic, Virus Latency, humans, latency, RNA, RNA splicing, romidepsin, transcription, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

ObjectivesReversing HIV-1 latency has been suggested as a strategy to eradicate HIV-1. We investigated the effect of romidepsin on the HIV transcription profile in participants from the REDUC part B clinical trial.DesignSeventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of the therapeutic vaccine Vacc-4x followed by treatment with three doses of romidepsin. Samples from nine study participants were available for HIV transcription profile analysis.MethodsRead-through, total (TAR), elongated (longLTR), polyadenylated (polyA) and multiply-spliced (Tat-Rev) HIV transcripts and total HIV DNA were quantified at baseline (visit 1) and 4 h after the second (visit 10b) and third (visit 11b) romidepsin infusions.ResultsRead-through, total, elongated, and polyadenylated HIV transcripts increased after romidepsin infusion (P = 0.020, P = 0.0078, P = 0.0039, P = 0.027, respectively), but no changes were observed in multiply-spliced HIV RNA or HIV DNA. No change was observed in the ratio of read-through/total HIV transcripts. The ratio of elongated/total HIV RNA increased after romidepsin (P = 0.016), whereas the ratio of polyadenylated/elongated HIV decreased. Both elongated HIV transcripts and total HIV DNA correlated negatively with the time to viral rebound after interruption of ART.ConclusionsIn these patients, romidepsin increased early events in HIV transcription (initiation and especially elongation), but had less effect on later stages (completion, multiple splicing) that may be required for comprehensive latency reversal and cell killing. Without cell death, increased HIV transcription before or after latency reversal may hasten viral rebound after therapy interruption.

Published
2019

12. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial

Author

Gruell, Henning, Gunst, Jesper D, Cohen, Yehuda Z, Pahus, Marie H, Malin, Jakob J, Platten, Martin, Millard, Katrina G, Tolstrup, Martin, Jones, R Brad, Conce Alberto, Winnifer D, Lorenzi, Julio C C, Oliveira, Thiago Y, Kümmerle, Tim, Suárez, Isabelle, Unson-O'Brien, Cecilia, Nogueira, Lilian, Olesen, Rikke, Østergaard, Lars, Nielsen, Henrik, Lehmann, Clara, Nussenzweig, Michel C, Fätkenheuer, Gerd, Klein, Florian, Caskey, Marina, and Søgaard, Ole S

Published
2022
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13. Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Author

Rosás-Umbert, Miriam, Gunst, Jesper D., Pahus, Marie H., Olesen, Rikke, Schleimann, Mariane, Denton, Paul W., Ramos, Victor, Ward, Adam, Kinloch, Natalie N., Copertino, Dennis C., Escribà, Tuixent, Llano, Anuska, Brumme, Zabrina L., Brad Jones, R., Mothe, Beatriz, Brander, Christian, Fox, Julie, Nussenzweig, Michel C., Fidler, Sarah, Caskey, Marina, Tolstrup, Martin, and Søgaard, Ole S.

Published
2022
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16. Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

Author

Gunst, Jesper D., Staerke, Nina B., Pahus, Marie H., Kristensen, Lena H., Bodilsen, Jacob, Lohse, Nicolai, Dalgaard, Lars S., Brønnum, Dorthe, Fröbert, Ole, Hønge, Bo, Johansen, Isik S., Monrad, Ida, Erikstrup, Christian, Rosendal, Regitze, Vilstrup, Emil, Mariager, Theis, Bove, Dorthe G., Offersen, Rasmus, Shakar, Shakil, Cajander, Sara, Jørgensen, Nis P., Sritharan, Sajitha S., Breining, Peter, Jespersen, Søren, Mortensen, Klaus L., Jensen, Mads L., Kolte, Lilian, Frattari, Giacomo S., Larsen, Carsten S., Storgaard, Merete, Nielsen, Lars P., Tolstrup, Martin, Sædder, Eva A., Østergaard, Lars J., Ngo, Hien T.T., Jensen, Morten H., Højen, Jesper F., Kjolby, Mads, and Søgaard, Ole S.

Published
2021
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17. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

Author

Hoffmann, Markus, Hofmann-Winkler, Heike, Smith, Joan C., Krüger, Nadine, Arora, Prerna, Sørensen, Lambert K., Søgaard, Ole S., Hasselstrøm, Jørgen Bo, Winkler, Michael, Hempel, Tim, Raich, Lluís, Olsson, Simon, Danov, Olga, Jonigk, Danny, Yamazoe, Takashi, Yamatsuta, Katsura, Mizuno, Hirotaka, Ludwig, Stephan, Noé, Frank, Kjolby, Mads, Braun, Armin, Sheltzer, Jason M., and Pöhlmann, Stefan

Published
2021
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19. HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Author

Offersen, Rasmus, Yu, Wen-Han, Scully, Eileen P., Julg, Boris, Euler, Zelda, Sadanand, Saheli, Garcia-Dominguez, Dario, Zheng, Lu, Rasmussen, Thomas A., Jennewein, Madeleine F., Linde, Caitlyn, Sassic, Jessica, Lofano, Giuseppe, Vigano, Selena, Stephenson, Kathryn E., Fischinger, Stephanie, Suscovich, Todd J., Lichterfeld, Mathias, Lauffenburger, Douglas, Rosenberg, Erik S., Allen, Todd, Altfeld, Marcus, Charles, Richelle C., Østergaard, Lars, Tolstrup, Martin, Barouch, Dan H., Søgaard, Ole S., and Alter, Galit

Published
2020
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21. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS‐CoV‐2 infection

Author

van der Sluis, Renée M, Cham, Lamin B, Gris‐Oliver, Albert, Gammelgaard, Kristine R, Pedersen, Jesper G, Idorn, Manja, Ahmadov, Ulvi, Hernandez, Sabina Sanches, Cémalovic, Ena, Godsk, Stine H, Thyrsted, Jacob, Gunst, Jesper D, Nielsen, Silke D, Jørgensen, Janni J, Bjerg, Tobias Wang, Laustsen, Anders, Reinert, Line S, Olagnier, David, Bak, Rasmus O, Kjolby, Mads, Holm, Christian K, Tolstrup, Martin, Paludan, Søren R, Kristensen, Lasse S, Søgaard, Ole S, and Jakobsen, Martin R

Published
2022
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22. TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes

Author

Schleimann, Mariane H., Kobberø, Maria-Louise, Vibholm, Line K., Kjær, Kathrine, Giron, Leila B., Busman-Sahay, Kathleen, Chan, Chi Ngai, Nekorchuk, Michael, Schmidt, Manuel, Wittig, Burghardt, Damsgaard, Tine E., Ahlburg, Peter, Hellfritzsch, Michel B., Zuwala, Kaja, Rothemejer, Frederik H., Olesen, Rikke, Schommers, Phillipp, Klein, Florian, Dweep, Harsh, Kossenkov, Andrew, Nyengaard, Jens R., Estes, Jacob D., Abdel-Mohsen, Mohamed, Østergaard, Lars, Tolstrup, Martin, Søgaard, Ole S., and Denton, Paul W.

Published
2019
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24. Single-Cell Analysis Reveals That CD47 mRNA Expression Correlates with Immune Cell Activation, Antiviral ISGs and Cytotoxicity.

Author

Cham, Lamin B., Rosas-Umbert, Miriam, Lin Lin, Tolstrup, Martin, and Søgaard, Ole S.

Subjects
GENE expression, REGULATOR genes, CD47 antigen, GENETIC regulation, INTERFERON gamma, PERFORINS
Abstract

Background/Aims: Immune cells are reported to upregulate CD47 during infection, however, the role of CD47 in innate and adaptive immune cells remains unclear. Methods: To bridge this knowledge gap, we analysed our single cell (sc)-RNA dataset along with other publicly available sc-RNA datasets from healthy controls, people with HIV-1 (PWH) and COVID-19 patients. We characterized each immune cell based on low, intermediate, and high expression of CD47. Results: Our analyses revealed that CD47high pDCs and monocytes exhibited relatively higher expression of IFN-α regulatory genes, antiviral interferon-stimulated genes (ISGs) and MHC-I associated genes compared to CD47inter. and CD47low cells. Furthermore, CD47high NK and CD8+ T cells showed higher expression of antiviral ISGs, as well as genes encoding for cytotoxic markers like granzyme B, perforin, granulysin, interferon gamma and NKG7. Additionally, CD47high CD8+ T cells expressed higher levels of PD-1 and LAG-3 genes. Lastly, we found that CD47high B cells had enriched expression of genes involved in cell activation and humoral responses. Conclusion: Overall, our analyses revealed that innate and adaptive immune cells expressing elevated activation and functional gene signatures also express higher CD47 levels. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Clinical Interventions in HIV Cure Research

Author

Rasmussen, Thomas Aagaard, Søgaard, Ole S., COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, Rezaei, Nima, Series Editor, Zhang, Linqi, editor, and Lewin, Sharon R., editor

Published
2018
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26. Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection

Author

Vibholm, Line, Schleimann, Mariane H., Højen, Jesper F., Benfield, Thomas, Offersen, Rasmus, Rasmussen, Katrine, Olesen, Rikke, Dige, Anders, Agnholt, Jørgen, Grau, Judith, Buzon, Maria, Wittig, Burghardt, Lichterfeld, Mathias, Petersen, Andreas Munk, Deng, Xutao, Abdel-Mohsen, Mohamed, Pillai, Satish K., Rutsaert, Sofie, Trypsteen, Wim, De Spiegelaere, Ward, Vandekerchove, Linos, Østergaard, Lars, Rasmussen, Thomas A., Denton, Paul W., Tolstrup, Martin, and Søgaard, Ole S.

Published
2017

27. SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection

Author

Baerends, Eva A.M., primary, Hvidt, Astrid K., additional, Reekie, Joanne, additional, Søgaard, Ole S., additional, Stærke, Nina B., additional, Raben, Dorthe, additional, Nielsen, Henrik, additional, Petersen, Kristine T., additional, Juhl, Maria R., additional, Johansen, Isik S., additional, Lindvig, Susan O., additional, Madsen, Lone W., additional, Wiese, Lothar, additional, Knudsen, Lene S., additional, Iversen, Mette B., additional, Benfield, Thomas, additional, Iversen, Kasper K., additional, Andersen, Sidsel D., additional, Juhl, Anna K., additional, Dietz, Lisa L., additional, Andreasen, Signe R., additional, Fischer, Thea K., additional, Erikstrup, Christian, additional, Valentiner-Branth, Palle, additional, Lundgren, Jens, additional, Østergaard, Lars, additional, Tolstrup, Martin, additional, Lundgren, J., additional, Østergaard, L., additional, Benfield, T., additional, Krohn-Dehli, L., additional, Petersen, D.K., additional, Fogh, K., additional, Højmark, E., additional, Iversen, K.K., additional, Bek, P., additional, Klastrup, V., additional, Larsen, F., additional, Rasmussen, S.H., additional, Schleimann, M.H., additional, Schieber, S., additional, Stærke, N.B., additional, Søndergaard, A., additional, Tarp, B., additional, Tousgaard, M., additional, Yehdego, Y., additional, Bodilsen, J., additional, Nielsen, H., additional, Petersen, K.T., additional, Ruwald, M., additional, Thisted, R.K., additional, Caspersen, S.F., additional, Iversen, M., additional, Knudsen, L.S., additional, Meyerhoff, J.L., additional, Sander, L.G., additional, Wiese, L., additional, Abildgaard, C., additional, Holden, I.K., additional, Johansen, N.E., additional, Johansen, I.S., additional, Larsen, L., additional, Lindvig, S.O., additional, Madsen, L.W., additional, Øvrehus, A., additional, Kruse, N.A., additional, Lomholdt, H., additional, Krause, T.G., additional, Valentiner-Branth, P., additional, Søborg, B., additional, Fischer, T.K., additional, Erikstrup, C., additional, Ostrowski, S.R., additional, Tolstrup, M., additional, Søgaard, O.S., additional, Raben, D., additional, Jylling, E., additional, Hougaard, D., additional, Andersen, S.D., additional, Lykkegaard, K., additional, Andreasen, S.R., additional, Baerends, E., additional, Dietz, L.L., additional, Hvidt, A.K., additional, Juhl, A.K., additional, Olesen, R., additional, Andersen, K.K., additional, Bannister, W., additional, Bjernved, C., additional, Elsing, T.W., additional, Esmann, F.V., additional, Ghafari, M.A., additional, Gravholdt, E., additional, Jakobsen, S.F., additional, Jakobsen, M.L., additional, Jensen, C.M., additional, Jensen, T.Ø., additional, Kristensen, D., additional, Kumar, L.R., additional, Matthews, C., additional, Normand, N., additional, Olsson, C., additional, Reekie, J., additional, Traytel, A., additional, Weide, T., additional, Hvas, A.M., additional, and Støvring, H., additional

Published
2023
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28. Effects of 24 Week Toll-Like Receptor 9 Agonist Treatment in HIV-1+ Individuals: a single-arm, phase 1B/2A trial

Author

Vibholm, Line K., Konrad, Christina V., Schleimann, Mariane H., Frattari, Giacomo, Winckelmann, Anni, Klastrup, Vibeke, Jensen, Nanna M., Jensen, Sanne S., Schmidt, Manuel, Wittig, Burghardt, Zuwala, Kaja, Mack, Katharina, Olesen, Rikke, Hua, Stephane, Lichterfeld, Mathias, Østergaard, Lars, Denton, Paul W., Tolstrup, Martin, and Søgaard, Ole S.

Published
2019
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29. Omicron Variant-Specific Serological Imprinting Following BA.1 or BA.4/5 Bivalent Vaccination and Previous SARS-CoV-2 Infection: A Cohort Study

Author

Baerends, Eva A M, primary, Reekie, Joanne, additional, Andreasen, Signe R, additional, Stærke, Nina B, additional, Raben, Dorthe, additional, Nielsen, Henrik, additional, Petersen, Kristine T, additional, Johansen, Isik S, additional, Lindvig, Susan O, additional, Madsen, Lone W, additional, Wiese, Lothar, additional, Iversen, Mette B, additional, Benfield, Thomas, additional, Iversen, Kasper K, additional, Larsen, Fredrikke D, additional, Andersen, Sidsel D, additional, Juhl, Anna K, additional, Dietz, Lisa L, additional, Hvidt, Astrid K, additional, Ostrowski, Sisse R, additional, Krause, Tyra G, additional, Østergaard, Lars, additional, Søgaard, Ole S, additional, Lundgren, Jens, additional, and Tolstrup, Martin, additional

Published
2023
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32. Omicron Variant-Specific Serological Imprinting Following BA.1 or BA.4/5 Bivalent Vaccination and Previous SARS-CoV-2 Infection:A Cohort Study

Author

Baerends, Eva A.M., Reekie, Joanne, Andreasen, Signe R., Stærke, Nina B., Raben, Dorthe, Nielsen, Henrik, Petersen, Kristine T., Johansen, Isik S., Lindvig, Susan O., Madsen, Lone W., Wiese, Lothar, Iversen, Mette B., Benfield, Thomas, Iversen, Kasper K., Larsen, Fredrikke D., Andersen, Sidsel D., Juhl, Anna K., Dietz, Lisa L., Hvidt, Astrid K., Ostrowski, Sisse R., Krause, Tyra G., Østergaard, Lars, Søgaard, Ole S., Lundgren, Jens, Tolstrup, Martin, Baerends, Eva A.M., Reekie, Joanne, Andreasen, Signe R., Stærke, Nina B., Raben, Dorthe, Nielsen, Henrik, Petersen, Kristine T., Johansen, Isik S., Lindvig, Susan O., Madsen, Lone W., Wiese, Lothar, Iversen, Mette B., Benfield, Thomas, Iversen, Kasper K., Larsen, Fredrikke D., Andersen, Sidsel D., Juhl, Anna K., Dietz, Lisa L., Hvidt, Astrid K., Ostrowski, Sisse R., Krause, Tyra G., Østergaard, Lars, Søgaard, Ole S., Lundgren, Jens, and Tolstrup, Martin

Abstract

Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, su, Background: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection. Conclusions: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of O

Published
2023

33. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence:the randomized phase 2a TITAN trial

Author

Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B.H., Lau, Jillian S.Y., Copertino, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, Søgaard, Ole S., Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B.H., Lau, Jillian S.Y., Copertino, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, and Søgaard, Ole S.

Abstract

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756., Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .

Published
2023

34. The Impact of Analytical Treatment Interruptions and Trial Interventions on Time to Viral Re-Suppression in People Living with HIV Restarting ART in Cure-Related Clinical Studies: A Systematic Review and Meta-Analysis

Author

Lee, Ming, primary, Eason, Miles, additional, Castagna, Antonella, additional, Galli, Laura, additional, De Scheerder, Marie-Angélique, additional, Riley, James L., additional, Tebas, Pablo, additional, Gunst, Jesper D., additional, Søgaard, Ole S., additional, Florence, Eric, additional, Kroon, Eugene, additional, De Souza, Mark, additional, Mothe, Beatriz, additional, Caskey, Marina, additional, and Fidler, Sarah, additional

Published
2023
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35. Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE)

Author

Stærke, Nina Breinholt, primary, Reekie, Joanne, additional, Johansen, Isik S, additional, Nielsen, Henrik, additional, Benfield, Thomas, additional, Wiese, Lothar, additional, Søgaard, Ole S, additional, Tolstrup, Martin, additional, Iversen, Kasper Karmark, additional, Tarp, Britta, additional, Larsen, Fredrikke Dam, additional, Larsen, Lykke, additional, Lindvig, Susan Olaf, additional, Holden, Inge Kristine, additional, Iversen, Mette Brouw, additional, Knudsen, Lene Surland, additional, Fogh, Kamille, additional, Jakobsen, Marie Louise, additional, Traytel, Anna Katrin, additional, Ostergaard, Lars, additional, and Lundgren, Jens, additional

Published
2022
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36. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial

Author

Rasmussen, Thomas A, Tolstrup, Martin, Brinkmann, Christel R, Olesen, Rikke, Erikstrup, Christian, Solomon, Ajantha, Winckelmann, Anni, Palmer, Sarah, Dinarello, Charles, Buzon, Maria, Lichterfeld, Mathias, Lewin, Sharon R, Østergaard, Lars, and Søgaard, Ole S

Published
2014
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46. Nanobody-mediated Complement Activation to Kill HIV-infected Cells

Author

Pedersen, Maria Lange, primary, Pedersen, Dennis Vestergaard, additional, Winkler, Mikael Becher Lykkegaard, additional, Olesen, Heidi Gytz, additional, Søgaard, Ole S, additional, Østergaard, Lars, additional, Laursen, Nick Stub, additional, Andersen, Anna Halling Folkmar, additional, and Tolstrup, Martin, additional

Published
2022
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49. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1:a phase 1b/2a, randomized trial

Author

Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I. Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D.Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, Søgaard, Ole S., Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I. Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D.Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, and Søgaard, Ole S.

Abstract

Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection (NCT03041012). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4+ T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4+ T cells and virus-specific CD8+ T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117 sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. In 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Furthermore, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4+ T cells containing intact HIV-1 provirus. At day 365, early 3BNC117 + romidepsin was associated with enhanced HIV-1 Gag-specific CD8+ T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in individuals whose pre-ART plasma HIV-1 envelope sequences were antibody sensitive. The results were not disaggregated by sex. Adverse events were

Published
2022

50. Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

Author

Hvidt, Astrid K., Baerends, Eva A. M., Søgaard, Ole S., Stærke, Nina B., Raben, Dorthe, Reekie, Joanne, Nielsen, Henrik, Johansen, Isik S., Wiese, Lothar, Benfield, Thomas L., Iversen, Kasper K., Mustafa, Ahmed B., Juhl, Maria R., Petersen, Kristine T., Ostrowski, Sisse R., Lindvig, Susan O., Rasmussen, Line D., Schleimann, Marianne H., Andersen, Sidsel D., Juhl, Anna K., Dietz, Lisa L., Andreasen, Signe R., Lundgren, Jens, Østergaard, Lars, Tolstrup, Martin, Hvidt, Astrid K., Baerends, Eva A. M., Søgaard, Ole S., Stærke, Nina B., Raben, Dorthe, Reekie, Joanne, Nielsen, Henrik, Johansen, Isik S., Wiese, Lothar, Benfield, Thomas L., Iversen, Kasper K., Mustafa, Ahmed B., Juhl, Maria R., Petersen, Kristine T., Ostrowski, Sisse R., Lindvig, Susan O., Rasmussen, Line D., Schleimann, Marianne H., Andersen, Sidsel D., Juhl, Anna K., Dietz, Lisa L., Andreasen, Signe R., Lundgren, Jens, Østergaard, Lars, and Tolstrup, Martin

Abstract

The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad prote

Published
2022

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