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1,025 results on '"BRANDER, CHRISTIAN"'

1. Converging and evolving immuno-genomic routes toward immune escape in breast cancer

Author

Blanco-Heredia, Juan, Souza, Carla Anjos, Trincado, Juan L., Gonzalez-Cao, Maria, Gonçalves-Ribeiro, Samuel, Gil, Sara Ruiz, Pravdyvets, Dmytro, Cedeño, Samandhy, Callari, Maurizio, Marra, Antonio, Gazzo, Andrea M., Weigelt, Britta, Pareja, Fresia, Vougiouklakis, Theodore, Jungbluth, Achim A., Rosell, Rafael, Brander, Christian, Tresserra, Francesc, Reis-Filho, Jorge S., Tiezzi, Daniel Guimarães, de la Iglesia, Nuria, Heyn, Holger, and De Mattos-Arruda, Leticia

Published
2024
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2. HIV T-cell immunogen design and delivery

Author

Brander, Christian and Hartigan-O’Connor, Dennis

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, Clinical Research, Sexually Transmitted Infections, Infectious Diseases, Clinical Trials and Supportive Activities, HIV/AIDS, Good Health and Well Being, AIDS Vaccines, Antiviral Agents, Epitopes, HIV Infections, HIV-1, Humans, T-Lymphocytes, Public Health and Health Services, Virology, Clinical sciences, Medical microbiology, Epidemiology
Abstract

Purpose of the reviewNot all T-cell responses against HIV are created equally and responses of certain epitope specificities have been associated with superior control of infection. These insights have spurred the development of a wide range of immunogen sequences, each with particular advantages and limitations.Recent findingsWe review some of the most advanced designs that have reached or are close to reaching human clinical trials, with a special focus on T-cell immunogen developed for therapeutic use. We also touch upon the importance of how immunogens are delivered and point out the lamentable fact that there is essentially no alignment between different designs and vaccine regimens, which is a major hindrance to accelerated advances in the field.SummaryThe design of an immunogen able to induce T-cell responses of adequate specificity and functionality is subject of a wide range of preclinical and clinical studies. Few designs have shown promise to date, but emerging data highlight the critical contribution of specificity to effective antiviral activity in vivo .

Published
2022

3. Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study

Author

Alarcón Soto, Yovaninna, Alemany, Andrea, Bailón, Lucía, Benet, Susana, Mitjà, Oriol, Mothe, Beatriz, Paredes, Roger, Sabato, Sofía, Suñer, Clara, Torrano, Pamela, Ubals, Maria, Boreika, Rytis, Brander, Christian, Carabelli, Julieta, Carrillo, Jorge, Gallemí, Marçal, Izquierdo-Useros, Nuria, Molina-Molina, Elisa, Moraes-Cardoso, Igor, Muñoz-Basagoiti, Jordana, Olvera, Alex, Perez-Zsolt, Daniel, Raïch-Regué, Dàlia, Coll, Pep, Fernández, Javier, Mendoza, Adrià, Pérez, Félix, Reguant, Joan, Rivero, Angel, Arando, Maider, Descalzo, Vicente, Néstor Garcia, Jorge, Monforte, Arnau, Álvarez, Patricia, Guedj, Jeremie, Marc, Aurélien, Marks, Michael, Alarcón-Soto, Yovaninna, Grifoni, Alba, Sette, Alessandro, and Moltó, José

Published
2024
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5. 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. T-Follicular-Like CD8+ T Cell Responses in Chronic HIV Infection Are Associated With Virus Control and Antibody Isotype Switching to IgG

Author

Romero-Martín, Luis, Tarrés-Freixas, Ferran, Pedreño-López, Núria, de la Concepción, Maria L Rodríguez, Cunyat, Francesc, Hartigan-O'Connor, Dennis, Carrillo, Jorge, Mothe, Beatriz, Blanco, Julià, Ruiz-Riol, Marta, Brander, Christian, and Olvera, Alex

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, Prevention, Vaccine Related, Immunization, HIV/AIDS, Vaccine Related (AIDS), Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Graft vs Host Disease, HIV Infections, Humans, Immunoglobulin Class Switching, Immunoglobulin G, Persistent Infection, HIV, humoral immune response, human immunodeficiency virus (HIV) control, T-follicular cytotoxic (Tfc) cells, viral control, Biochemistry and cell biology, Genetics
Abstract

T cell responses are considered critical for the in vivo control of HIV, but the contribution of different T cell subsets to this control remains unclear. Using a boosted flow cytometric approach that is able to differentiate CD4+ and CD8+ T cell Th1/Tc1, Th2/Tc2, Th17/Tc17, Treg and Tfh/Tfc-like HIV-specific T cell populations, we identified CD8+ Tfc responses that were related to HIV plasma viral loads and associated with rate of antibody isotype class switching to IgG. This favorable balance towards IgG responses positively correlated with increased virus neutralization, higher avidity of neutralizing antibodies and more potent antibody-dependent cell cytotoxicity (ADCC) in PBMCs from HIV controllers compared to non-controllers. Our results identified the CD8+ Tfc-like T-cell response as a component of effective virus control which could possibly be exploited therapeutically.

Published
2022

7. Vagus nerve dysfunction in the post–COVID-19 condition: a pilot cross-sectional study

Author

José, Muñoz-Moreno, Carmina, Rodríguez-Fumaz, Anna, Prats, Carla, Estany, Nuria, Vallejo, Roger, Villuendas, Julia, Aranyó, Toni, Marín, Julia, Mitjans, Ivette, Casafont, Lladós, Gemma, Massanella, Marta, Coll-Fernández, Roser, Rodríguez, Raúl, Hernández, Electra, Lucente, Giuseppe, López, Cristina, Loste, Cora, Santos, José Ramón, España-Cueto, Sergio, Nevot, Maria, Muñoz-López, Francisco, Silva-Arrieta, Sandra, Brander, Christian, Durà, Maria José, Cuadras, Patricia, Bechini, Jordi, Tenesa, Montserrat, Martinez-Piñeiro, Alicia, Herrero, Cristina, Chamorro, Anna, Garcia, Anna, Grau, Eulalia, Clotet, Bonaventura, Paredes, Roger, and Mateu, Lourdes

Published
2024
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8. Immunology

Author

Hartigan-O’Connor, Dennis J., primary and Brander, Christian, additional

Published
2023
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9. Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

Author

Kobayashi-Ishihara, Mie, Frazão Smutná, Katarína, Alonso, Florencia E., Argilaguet, Jordi, Esteve-Codina, Anna, Geiger, Kerstin, Genescà, Meritxell, Grau-Expósito, Judith, Duran-Castells, Clara, Rogenmoser, Selina, Böttcher, René, Jungfleisch, Jennifer, Oliva, Baldomero, Martinez, Javier P., Li, Manqing, David, Michael, Yamagishi, Makoto, Ruiz-Riol, Marta, Brander, Christian, Tsunetsugu-Yokota, Yasuko, Buzon, Maria J., Díez, Juana, and Meyerhans, Andreas

Published
2023
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10. Cytomegalovirus mediates expansion of IL-15-responsive innate-memory cells with SIV killing function

Author

Méndez-Lagares, Gema, Chin, Ning, Chang, WL William, Lee, Jaewon, Rosás-Umbert, Míriam, Kieu, Hung T, Merriam, David, Lu, Wenze, Kim, Sungjin, Adamson, Lourdes, Brander, Christian, Luciw, Paul A, Barry, Peter A, and Hartigan-O’Connor, Dennis J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Prevention, Immunization, Sexually Transmitted Infections, Vaccine Related (AIDS), Emerging Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Good Health and Well Being, Animals, CD8-Positive T-Lymphocytes, Cytomegalovirus, Female, Immunity, Innate, Immunologic Memory, Interleukin-15, Killer Cells, Natural, Macaca mulatta, Male, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Simian immunodeficiency virus, Cellular immune response, Infectious disease, Innate immunity, T cells, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Interindividual immune variability is driven predominantly by environmental factors, including exposure to chronic infectious agents such as cytomegalovirus (CMV). We investigated the effects of rhesus CMV (RhCMV) on composition and function of the immune system in young macaques. Within months of infection, RhCMV was associated with impressive changes in antigen presenting cells, T cells, and NK cells-and marked expansion of innate-memory CD8+ T cells. These cells express high levels of NKG2A/C and the IL-2 and IL-15 receptor beta chain, CD122. IL-15 was sufficient to drive differentiation of the cells in vitro and in vivo. Expanded NKG2A/C+CD122+CD8+ T cells in RhCMV-infected macaques, but not their NKG2-negative counterparts, were endowed with cytotoxicity against class I-deficient K562 targets and prompt IFN-γ production in response to stimulation with IL-12 and IL-18. Because RhCMV clone 68-1 forms the viral backbone of RhCMV-vectored SIV vaccines, we also investigated immune changes following administration of RhCMV 68-1-vectored SIV vaccines. These vaccines led to impressive expansion of NKG2A/C+CD8+ T cells with capacity to inhibit SIV replication ex vivo. Thus, CMV infection and CMV-vectored vaccination drive expansion of functional innate-like CD8 cells via host IL-15 production, suggesting that innate-memory expansion could be achieved by other vaccine platforms expressing IL-15.

Published
2021

12. TL1A–DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1–Specific T Cell Responses

Author

Oriol-Tordera, Bruna, Olvera, Alex, Duran-Castells, Clara, Llano, Anuska, Mothe, Beatriz, Massanella, Marta, Dalmau, Judith, Ganoza, Carmela, Sanchez, Jorge, Calle, Maria Luz, Clotet, Bonaventura, Martinez-Picado, Javier, Negredo, Eugènia, Blanco, Julià, Hartigan-O'Connor, Dennis, Brander, Christian, and Ruiz-Riol, Marta

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, Genetics, Clinical Research, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Antibodies, Monoclonal, Murine-Derived, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV Infections, HIV-1, Humans, Male, Mice, Receptors, Tumor Necrosis Factor, Member 25, Tumor Necrosis Factor Ligand Superfamily Member 15, Biochemistry and cell biology
Abstract

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1-infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cells/mm3, n = 47) and relatively controlled disease (pVL

Published
2020

13. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial

Author

Bailón, Lucia, Llano, Anuska, Cedeño, Samandhy, Escribà, Tuixent, Rosás-Umbert, Miriam, Parera, Mariona, Casadellà, Maria, Lopez, Miriam, Pérez, Francisco, Oriol-Tordera, Bruna, Ruiz-Riol, Marta, Coll, Josep, Perez, Felix, Rivero, Àngel, Leselbaum, Anne R., McGowan, Ian, Sengupta, Devi, Wee, Edmund G., Hanke, Tomáš, Paredes, Roger, Alarcón-Soto, Yovaninna, Clotet, Bonaventura, Noguera-Julian, Marc, Brander, Christian, Molto, Jose, and Mothe, Beatriz

Published
2022
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14. Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Author

Ainsua-Enrich, Erola, Pedreño-Lopez, Núria, Bracke, Carmen, Ávila-Nieto, Carlos, Rodríguez de la Concepción, María Luisa, Pradenas, Edwards, Trinité, Benjamin, Marfil, Silvia, Miranda, Cristina, González, Sandra, Toledo, Ruth, Font, Marta, Benet, Susana, Escribà, Tuixent, Jimenez-Moyano, Esther, Peña, Ruth, Cedeño, Samandhy, Prado, Julia G., Mothe, Beatriz, Brander, Christian, Izquierdo-Useros, Nuria, Vergara-Alert, Julia, Segalés, Joaquim, Massanella, Marta, Benitez, Rosa María, Romero, Alba, Molina-Morant, Daniel, Blanco, Julià, Clotet, Bonaventura, Mateu, Lourdes, Pedro-Botet, María Luisa, and Carrillo, Jorge

Published
2022
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15. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection

Author

Adland, Emily, Hill, Matilda, Lavandier, Nora, Csala, Anna, Edwards, Anne, Chen, Fabian, Radkowski, Marek, Kowalska, Justyna D, Paraskevis, Dimitrios, Hatzakis, Angelos, Valenzuela-Ponce, Humberto, Pfafferott, Katja, Williams, Ian, Pellegrino, Pierre, Borrow, Persephone, Mori, Masahiko, Rockstroh, Jürgen, Prado, Julia G, Mothe, Beatriz, Dalmau, Judith, Martinez-Picado, Javier, Tudor-Williams, Gareth, Frater, John, Stryhn, Anette, Buus, Soren, Teran, Gustavo Reyes, Mallal, Simon, John, Mina, Buchbinder, Susan, Kirk, Gregory, Martin, Jeffrey, Michael, Nelson, Fellay, Jacques, Deeks, Steve, Walker, Bruce, Avila-Rios, Santiago, Cole, David, Brander, Christian, Carrington, Mary, and Goulder, Philip

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, HIV/AIDS, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Genes, MHC Class I, HIV Infections, HIV-1, HLA-B27 Antigen, Humans, Immunodominant Epitopes, Viral Load, gag Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, CD8(+) T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, human immunodeficiency virus, CD8+ T cell, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

Published
2018

16. 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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17. Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

Author

Borgognone, Alessandra, Noguera-Julian, Marc, Oriol, Bruna, Noël-Romas, Laura, Ruiz-Riol, Marta, Guillén, Yolanda, Parera, Mariona, Casadellà, Maria, Duran, Clara, Puertas, Maria C., Català-Moll, Francesc, De Leon, Marlon, Knodel, Samantha, Birse, Kenzie, Manzardo, Christian, Miró, José M., Clotet, Bonaventura, Martinez-Picado, Javier, Moltó, José, Mothe, Beatriz, Burgener, Adam, Brander, Christian, and Paredes, Roger

Published
2022
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20. Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses

Author

Sandström, Eric, Darbyshire, Janet, Post, Frank, Conlon, Christopher, Anderson, Jane, Maini, Mala, Peto, Timothy, Sasieni, Peter, Miller, Veronica, Weller, Ian, Fidler, Sarah, Frater, John, Babiker, Abdel, Stöhr, Wolfgang, Pett, Sarah, Dorrell, Lucy, Pace, Matthew, Olejniczak, Natalia, Brown, Helen, Robinson, Nicola, Kopycinski, Jakub, Yang, Hongbing, Hanke, Tomáš, Crook, Alison, Kaye, Steven, McClure, Myra, Erlwein, Otto, Lovell, Andrew, Khan, Maryam, Gabrielle, Michelle, Bennett, Rachel, Sy, Aminata, Gregory, Adam, Hudson, Fleur, Russell, Charlotte, Wood, Gemma, Box, Hanna, Kingsley, Cherry, Topping, Katie, Lever, Andrew, Wills, Mark, Fun, Axel, Bandara, Mikaila, Kelly, Damian, Collins, Simon, Markham, Alex, Rauchenberger, Mary, Sowunmi, Yinka, Shidfar, Shaadi, Hague, Dominic, Nelson, Mark, Cerrone, Maddalena, Castrillo Martinez, Nadia, Barber, Tristan, Schoolmeesters, Alexandra, Weaver, Christine, Thunder, Orla, Rowlands, Jane, Higgs, Christopher, Fedele, Serge, Bracchi, Margherita, Thomas, Lervina, Bourke, Peter, Nwokolo, Nneka, Lawrenson, Gaynor, Fiorino, Marzia, Lukha, Hinal, Kinloch-de Loes, Sabine, Johnson, Margaret, Nightingale, Alice, Ngwu, Nnenna, Byrne, Patrick, Cuthbertson, Zoe, Jones, Martin, Fernandez, Tina, Clarke, Amanda, Fisher, Martin, Gleig, Rebecca, Trevitt, Vittorio, Fitzpatrick, Colin, Adams, Tanya, Finnerty, Fiounnuala, Thornhill, John, Lewis, Heather, Kuldanek, Kristin, Fox, Julie, Lwanga, Julianne, Uzu, Hiromi, Lee, Ming, Merle, Simon, O’Rourke, Patrick, Jendrulek, Isabel, Zarko Flynn, Taras, Taylor, Mark, Manuel Tiraboschi, Juan, Murray, Tammy, Llano, Anuska, Cedeño, Samandhy, von Delft, Annette, Corcuera, Angelica, Gillespie, Geraldine M., Knox, Andrew, Leneghan, Darren B., Mothe, Beatriz, Mak, Johnson, Brander, Christian, and Ternette, Nicola

Published
2021
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23. Immunology

Author

Hartigan-O’Connor, Dennis J., primary and Brander, Christian, additional

Published
2021
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25. Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish the rare phenotype of elite control in adolescents living with HIV from viraemic non-progressors

Author

Vieira, Vinicius A., Millar, Jane, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Guash, Claudia Fortuny, Peluso, Denise, Thomé, Beatriz, Garcia-Guerrero, Maria C., Puertas, Mari C., Bamford, Alasdair, Brander, Christian, Carrington, Mary, Martinez-Picado, Javier, Frater, John, Tudor-Williams, Gareth, and Goulder, Philip

Published
2021
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26. Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors

Author

Vieira, Vinicius A., Millar, Jane, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Guash, Claudia Fortuny, Peluso, Denise, Thomé, Beatriz, Garcia-Guerrero, Maria C., Puertas, Mari C., Bamford, Alasdair, Brander, Christian, Carrington, Mary, Martinez-Picado, Javier, Frater, John, Tudor-Williams, Gareth, and Goulder, Philip

Published
2022
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27. Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection

Author

Guillén, Yolanda, Noguera-Julian, Marc, Rivera, Javier, Casadellà, Maria, Zevin, Alexander S., Rocafort, Muntsa, Parera, Mariona, Rodríguez, Cristina, Arumí, Marçal, Carrillo, Jorge, Mothe, Beatriz, Estany, Carla, Coll, Josep, Bravo, Isabel, Herrero, Cristina, Saz, Jorge, Sirera, Guillem, Torrella, Ariadna, Navarro, Jordi, Crespo, Manuel, Negredo, Eugènia, Brander, Christian, Blanco, Julià, Calle, Maria Luz, Klatt, Nichole R., Clotet, Bonaventura, and Paredes, Roger

Published
2019
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28. Vagus nerve dysfunction in the post–COVID-19 condition: a pilot cross-sectional study

Author

Lladós, Gemma, primary, Massanella, Marta, additional, Coll-Fernández, Roser, additional, Rodríguez, Raúl, additional, Hernández, Electra, additional, Lucente, Giuseppe, additional, López, Cristina, additional, Loste, Cora, additional, Santos, José Ramón, additional, España-Cueto, Sergio, additional, Nevot, Maria, additional, Muñoz-López, Francisco, additional, Silva-Arrieta, Sandra, additional, Brander, Christian, additional, Durà, Maria José, additional, Cuadras, Patricia, additional, Bechini, Jordi, additional, Tenesa, Montserrat, additional, Martinez-Piñeiro, Alicia, additional, Herrero, Cristina, additional, Chamorro, Anna, additional, Garcia, Anna, additional, Grau, Eulalia, additional, Clotet, Bonaventura, additional, Paredes, Roger, additional, Mateu, Lourdes, additional, José, Muñoz-Moreno, additional, Carmina, Rodríguez-Fumaz, additional, Anna, Prats, additional, Carla, Estany, additional, Nuria, Vallejo, additional, Roger, Villuendas, additional, Julia, Aranyó, additional, Toni, Marín, additional, Julia, Mitjans, additional, and Ivette, Casafont, additional

Published
2023
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29. HIV T-Cell Vaccines

Author

Mothe, Beatriz, Brander, Christian, 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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30. Definition of the viral targets of protective HIV-1-specific T cell responses

Author

Mothe, Beatriz, Llano, Anuska, Ibarrondo, Javier, Daniels, Marcus, Miranda, Cristina, Zamarreño, Jennifer, Bach, Vanessa, Zuniga, Rosario, Pérez-Álvarez, Susana, Berger, Christoph T, Puertas, Maria C, Martinez-Picado, Javier, Rolland, Morgane, Farfan, Marilu, Szinger, James J, Hildebrand, William H, Yang, Otto O, Sanchez-Merino, Victor, Brumme, Chanson J, Brumme, Zabrina L, Heckerman, David, Allen, Todd M, Mullins, James I, Gómez, Guadalupe, Goulder, Philip J, Walker, Bruce D, Gatell, Jose M, Clotet, Bonaventura, Korber, Bette T, Sanchez, Jorge, and Brander, Christian

Abstract

Abstract Background The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. Methods Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. Results For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. Conclusions The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.

Published
2011

31. Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels

Author

Elizalde-Torrent, Aleix, primary, Borgognone, Alessandra, additional, Casadellà, Maria, additional, Romero-Martin, Luis, additional, Escribà, Tuixent, additional, Parera, Mariona, additional, Rosales-Salgado, Yaiza, additional, Díaz-Pedroza, Jorge, additional, Català-Moll, Francesc, additional, Noguera-Julian, Marc, additional, Brander, Christian, additional, Paredes, Roger, additional, and Olvera, Alex, additional

Published
2023
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33. Immunology

Author

Hartigan-O’Connor, Dennis J., primary and Brander, Christian, additional

Published
2019
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34. Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection

Author

Draenert, Rika, Le Gall, Sylvie, Pfafferott, Katja J, Leslie, Alasdair J, Chetty, Polan, Brander, Christian, Holmes, Edward C, Chang, Shih-Chung, Feeney, Margaret E, Addo, Marylyn M, Ruiz, Lidia, Ramduth, Danni, Jeena, Prakash, Altfeld, Marcus, Thomas, Stephanie, Tang, Yanhua, Verrill, Cori L, Dixon, Catherine, Prado, Julia G, Kiepiela, Photini, Martinez-Picado, Javier, Walker, Bruce D, and Goulder, Philip JR

Subjects
Prevention, Genetics, Infectious Diseases, HIV/AIDS, Vaccine Related, Immunization, Vaccine Related (AIDS), Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Alleles, Amino Acid Sequence, Antigen Presentation, Base Sequence, Clone Cells, DNA, Viral, Epitopes, Gene Products, gag, Genetic Variation, HIV Antigens, HIV Infections, HIV-1, HLA-B Antigens, Humans, Molecular Sequence Data, Mutation, Sequence Homology, Amino Acid, T-Lymphocytes, Cytotoxic, Medical and Health Sciences, Immunology
Abstract

Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.

Published
2004

35. Determinants of HIV-1 Mutational Escape From Cytotoxic T Lymphocytes

Author

Yang, Otto O, Sarkis, Phuong Thi Nguyen, Ali, Ayub, Harlow, Jason D, Brander, Christian, Kalams, Spyros A, and Walker, Bruce D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Infectious Diseases, Sexually Transmitted Infections, Immunization, Vaccine Related, Good Health and Well Being, Amino Acid Sequence, Cell Line, Epitopes, Gene Products, gag, Gene Products, nef, HIV Reverse Transcriptase, HIV-1, Humans, Molecular Sequence Data, Mutation, T-Lymphocytes, Cytotoxic, nef Gene Products, Human Immunodeficiency Virus, cellular immunity, T cell receptor, antigenic variation, T cell receptor specificity, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to study in vivo. Here we used a controlled in vitro system to evaluate the ability of HIV-1 to escape from CTL clones, finding that virus replicating under selective pressure rapidly can develop phenotypic resistance associated with genotypic changes. Escape varied between clones recognizing the same Gag epitope or different Gag and RT epitopes, indicating the influence of the T cell receptor on pressure and fitness costs. Gag and RT escape mutations were monoclonal intra-epitope substitutions, indicating limitation by fitness constraints in structural proteins. In contrast, escape from Nef-specific CTL was more rapid and consistent, marked by a polyclonal mixture of epitope point mutations and upstream frameshifts. We conclude that incomplete viral suppression by CTL can result in rapid emergence of immune escape, but the likelihood is strongly determined by factors influencing the fitness costs of the particular epitope targeted and the ability of responding CTL to recognize specific epitope variants.

Published
2003

36. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

Author

Altfeld, Marcus, Rosenberg, Eric S, Shankarappa, Raj, Mukherjee, Joia S, Hecht, Frederick M, Eldridge, Robert L, Addo, Marylyn M, Poon, Samuel H, Phillips, Mary N, Robbins, Gregory K, Sax, Paul E, Boswell, Steve, Kahn, James O, Brander, Christian, Goulder, Philip JR, Levy, Jay A, Mullins, James I, and Walker, Bruce D

Subjects
Vaccine Related, Prevention, HIV/AIDS, Infectious Diseases, Immunization, Infection, Inflammatory and immune system, Good Health and Well Being, Acute Disease, Amino Acid Sequence, Antiretroviral Therapy, Highly Active, Base Sequence, Cohort Studies, DNA Primers, Epitopes, Female, Genetic Variation, HIV Infections, HIV Seropositivity, HIV-1, Humans, Immunity, Cellular, Longitudinal Studies, Male, Molecular Sequence Data, RNA, Viral, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer, Time Factors, cytotoxic T lymphocytes, T helper cell responses, viral evolution, cytotoxic T lymphocyte epitopes, human leukocyte antigen, Medical and Health Sciences, Immunology
Abstract

Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.

Published
2001

37. Gut Microbiota Linked to Sexual Preference and HIV Infection

Author

Noguera-Julian, Marc, Rocafort, Muntsa, Guillén, Yolanda, Rivera, Javier, Casadellà, Maria, Nowak, Piotr, Hildebrand, Falk, Zeller, Georg, Parera, Mariona, Bellido, Rocío, Rodríguez, Cristina, Carrillo, Jorge, Mothe, Beatriz, Coll, Josep, Bravo, Isabel, Estany, Carla, Herrero, Cristina, Saz, Jorge, Sirera, Guillem, Torrela, Ariadna, Navarro, Jordi, Crespo, Manel, Brander, Christian, Negredo, Eugènia, Blanco, Julià, Guarner, Francisco, Calle, Maria Luz, Bork, Peer, Sönnerborg, Anders, Clotet, Bonaventura, and Paredes, Roger

Published
2016
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39. Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction

Author

Duran-Castells, Clara, primary, Llano, Anuska, additional, Kawana-Tachikawa, Ai, additional, Prats, Anna, additional, Martinez-Zalacain, Ignacio, additional, Kobayashi-Ishihara, Mie, additional, Oriol-Tordera, Bruna, additional, Peña, Ruth, additional, Gálvez, Cristina, additional, Silva-Arrieta, Sandra, additional, Clotet, Bonaventura, additional, Riveira-Muñoz, Eva, additional, Ballana, Esther, additional, Prado, Julia G., additional, Martinez-Picado, Javier, additional, Sanchez, Jorge, additional, Mothe, Beatriz, additional, Hartigan-O’Connor, Dennis, additional, Wyss-Coray, Tony, additional, Meyerhans, Andreas, additional, Gisslén, Magnus, additional, Price, Richard W., additional, Soriano-Mas, Carles, additional, Muñoz-Moreno, José Antonio, additional, Brander, Christian, additional, and Ruiz-Riol, Marta, additional

Published
2023
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42. Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

Author

Ruiz-Riol, Marta, Llano, Anuska, Ibarrondo, Javier, Zamarreño, Jennifer, Yusim, Karina, Bach, Vanessa, Mothe, Beatriz, Perez-Alvarez, Susana, Fernandez, Marco A., Requena, Gerard, Meulbroek, Michael, Pujol, Ferran, Leon, Agathe, Cobarsi, Patricia, Korber, Bette T., Clotet, Bonaventura, Ganoza, Carmela, Sanchez, Jorge, Coll, Josep, and Brander, Christian

Published
2015

45. Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

Author

Kobayashi-Ishihara, Mie, primary, Smutná, Katarína Frazão, additional, Alonso, Florencia E., additional, Argilaguet, Jordi, additional, Esteve-Codina, Anna, additional, Geiger, Kerstin, additional, Genescà, Meritxell, additional, Grau-Expósito, Judith, additional, Duran-Castells, Clara, additional, Rogenmoser, Selina, additional, Böttcher, René, additional, Jungfleisch, Jennifer, additional, Oliva, Baldomero, additional, Martinez, Javier P., additional, Li, Manqing, additional, David, Michael, additional, Yamagishi, Makoto, additional, Ruiz-Riol, Marta, additional, Brander, Christian, additional, Tsunetsugu-Yokota, Yasuko, additional, Buzon, Maria J., additional, Díez, Juana, additional, and Meyerhans, Andreas, additional

Published
2022
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46. Strong sex bias in elite control of paediatric HIV infection

Author

Vieira, Vinicius A., Zuidewind, Peter, Muenchhoff, Maximilian, Roider, Julia, Millar, Jane, Clapson, Margaret, Van Zyl, Anriette, Shingadia, Delane, Adland, Emily, Athavale, Rohin, Grayson, Nicholas, Ansari, M. Azim, Brander, Christian, Guash, Claudia Fortuny, Naver, Lars, Puthanakit, Thanyawee, Songtaweesin, Wipaporn Natalie, Ananworanich, Jintanat, Peluso, Denise, Thomé, Beatriz, Pinto, Jorge, Jooste, Pieter, Tudor-Williams, Gareth, Cotton, Mark F., and Goulder, Philip

Published
2019
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48. Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection

Author

Leal, Lorna, Guardo, Alberto C., Morón-López, Sara, Salgado, Maria, Mothe, Beatriz, Heirman, Carlo, Pannus, Pieter, Vanham, Guido, van den Ham, Henk Jan, Gruters, Rob, Andeweg, Arno, Van Meirvenne, Sonja, Pich, Judit, Arnaiz, Joan Albert, Gatell, Josep M., Brander, Christian, Thielemans, Kris, Martínez-Picado, Javier, Plana, Montserrat, and García, Felipe

Published
2018
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49. Immunology

Author

Hartigan-O’Connor, Dennis J., primary and Brander, Christian, additional

Published
2017
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50. Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution

Author

Benet, Susana, primary, Blanch-Lombarte, Oscar, additional, Ainsua-Enrich, Erola, additional, Pedreño-Lopez, Núria, additional, Muñoz-Basagoiti, Jordana, additional, Raïch-Regué, Dàlia, additional, Perez-Zsolt, Daniel, additional, Peña, Ruth, additional, Jiménez, Esther, additional, de la Concepción, María Luisa Rodríguez, additional, Ávila, Carlos, additional, Cedeño, Samandhy, additional, Escribà, Tuixent, additional, Romero-Martín, Luis, additional, Alarcón-Soto, Yovaninna, additional, Rodriguez-Lozano, Gabriel Felipe, additional, Miranda, Cristina, additional, González, Sandra, additional, Bailón, Lucía, additional, Blanco, Julià, additional, Massanella, Marta, additional, Brander, Christian, additional, Clotet, Bonaventura, additional, Paredes, Roger, additional, Esteve, María, additional, Izquierdo-Useros, Nuria, additional, Carrillo, Jorge, additional, Prado, Julia G, additional, Moltó, José, additional, and Mothe, Beatriz, additional

Published
2022
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