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2. 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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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, Human Genome, Genetics, Infectious Diseases, Immunization, Sexually Transmitted Infections, Vaccine Related, HIV/AIDS, 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

4. 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, Infectious Diseases, Sexually Transmitted Infections, Immunization, Vaccine Related, Prevention, 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

6. 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, Sexually Transmitted Infections, Genetics, Prevention, HIV/AIDS, Infectious Diseases, Clinical Research, Aetiology, 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

7. 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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8. Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Garibaldi, Brian T., Albertson, Timothy E., Sandrock, Christian, Lee, Janet S., Looney, Mark R., Tapson, Victor F., Wiysonge, Charles Shey, Velarde, Luis Humberto Anaya, Backenroth, Daniel, Bhushanan, Jisha, Brandenburg, Börries, Cárdenas, Vicky, Chen, Bohang, Chen, Fei, Chetty, Polan, Chu, Pei-Ling, Cooper, Kimberly, Custers, Jerome, Delanghe, Hilde, Duca, Anna, Henrick, Tracy, Juraszek, Jarek, Nalpas, Catherine, Peeters, Monika, Pinheiro, Jose, Roels, Sanne, Ryser, Martin F., Salas, Jose, Santoro Matias, Samantha, Scheys, Ilse, Shetty, Pallavi, Shukarev, Georgi, Stoddard, Jeffrey, Talloen, Willem, Tran, NamPhuong, Vaissiere, Nathalie, van Son-Palmen, Elisabeth, Xu, Jiajun, Goecker, Erin A., Greninger, Alexander L., Jerome, Keith R., Roychoudhury, Pavitra, Takuva, Simbarashe G., Accini Mendoza, Jose Luis, Achtyes, Eric, Ahsan, Habibul, Alhatemi, Azhar, Allen, Nancy, Arribas, Jose R., Bahrami, Ghazaleh, Bailon, Lucia, Bajwa, Ali, Baker, Jonathan, Baron, Mira, Benet, Susana, Berdaï, Driss, Berger, Patrick, Bertoch, Todd, Bethune, Claire, Bevilacqua, Sybille, Biagioni Santos, Maria Silvia, Binnian, Ian, Bisnauthsing, Karen, Boivin, Jean-Marc, Bollen, Hilde, Bonnet, Sandrine, Borobia, Alberto M., Botelho-Nevers, Elisabeth, Bright, Phil, Britten, Vianne, Brown, Claire, Buadi, Amanda, Buntinx, Erik, Burgess, Lesley, Bush, Larry, Capeding, Maria Rosario, Carr, Quito Osuna, Carrasco Mas, Amparo, Catala, Hélène, Cathie, Katrina, Caudill, T. Shawn, Cereto Castro, Fernando, Chau, Kénora, Chavoustie, Steven, Chowdhury, Marie, Chronos, Nicolas, Cicconi, Paola, Cifuentes, Liliana, Cobo, Sara Maria, Collins, Helen, Colton, Hayley, Cuaño, Carlos Rolando G., D'Onofrio, Valentino, Dargan, Paul, Darton, Thomas, Deane, Peter, Del Pozo, Jose Luis, Derdelinckx, Inge, Desai, Amisha, Dever, Michael, Díaz-Pollán, Beatriz, DiBuono, Mark, Doust, Matthew, Duncan, Christopher, Echave-Sustaeta, Jose Maria, Eder, Frank, Ellis, Kimberly, Elzi, Stanton, Emmett, Stevan, Engelbrecht, Johannes, Evans, Mim, Farah, Theo, Felton, Timothy, Ferreira, João Pedro, Floutier, Catherine, Flume, Patrick, Ford, Stacy, Fragoso, Veronica, Freedman, Andrew, Frentiu, Emilia, Galloway, Christopher, Galtier, Florence, Garcia Diaz, Julia, García García, Irene, Garcia, Alcaide, Gardener, Zoe, Gauteul, Pascale, Geller, Steven, Gibson, Andrew, Gillet, Claudia, Girerd, Nicolas, Girodet, Pierre-Olivier, Gler, Maria Tarcela, Glover, Richard, Go, Herschel Don D., Gokani, Karishma, Gonthier, Damien, Green, Christopher, Greenberg, Richard, Griffin, Carl, Grobbelaar, Coert, Guancia, Adonis, Hakkarainen, Gloria, Harris, James, Hassman, Michael, Heimer, Deirdre, Hellstrom-Louw, Elizabeth, Herades, Yoan, Holroyd, Christopher, Hussen, Nazreen, Isidro, Marie Grace Dawn, Jackson, Yvonne, Jain, Manish, João Filho, Esaú Custódio, Johnson, Daniel, Jones, Ben, Joseph, Natasha, Jumeras, Analyn, Junquera, Patricia, Kellett-Wright, Johanna, Kennedy, Patrick, Kilgore, Paul E., Kim, Kenneth, Kimmel, Murray, Konis, George, Kutner, Mark, Lacombe, Karine, Launay, Odile, Lazarus, Rajeka, Lederman, Samuel, Lefebvre, Gigi, Lennon Collins, Katrina, Leroux-Roels, Isabel, Lim, Kenneth Wilson O., Lins, Muriel, Liu, Edward, Llewelyn, Martin, Mahomed, Akbar, Maia, Bernardo Porto, Marín-Candon, Alícia, Martínez-Gómez, Xavier, Martinot, Jean Benoit, Mazzella, Andrea, McCaughan, Frank, McCormack, Louise, McGettigan, John, Mehra, Purvi, Mejeur, Rhonda, Miller, Vicki, Mills, Anthony, Molto Marhuenda, Jose, Moodley, Prebashan, Mora-Rillo, Marta, Mothe, Beatriz, Mullan, Daniel, Munro, Alasdair, Myers, Paul, Nell, Jeremy, Newman Lobato Souza, Tamara, O'Halloran, Jane A., Ochoa Mazarro, Maria Dolores, Oliver, Abigail, Onate Gutierrez, Jose Millan, Ortega, Jessica, Oshita, Masaru, Otero Romero, Susana, Overcash, Jeffrey Scott, Owens, Daniel, Packham, Alice, Pacurar, Mihaela, Paiva de Sousa, Leonardo, Palfreeman, Adrian, Pallares, Christian José, Patel, Rahul, Patel, Suchet, Pelkey, Leslie, Peluso, Denise, Penciu, Florentina, Pinto, S. Jerry, Pounds, Kevin, Pouzar, Joe, Pragalos, Antoinette, Presti, Rachel, Price, David, Qureshi, Ehsaan, Ramalho Madruga, José Valdez, Ramesh, Mayur, Rankin, Bruce, Razat, Béatrice, Riegel Santos, Breno, Riesenberg, Robert, Riffer, Ernie, Roche, Siobhan, Rose, Katie, Rosellini, Pietro, Rossignol, Patrick, Safirstein, Beth, Salazar, Hernan, Sanchez Vallejo, Gregorio, Santhosh, Smrithi, Seco-Meseguer, Enrique, Seep, Michael, Sherry, Emma, Short, Philip, Soentjens, Patrick, Solis, Joel, Soriano Viladomiu, Alejandro, Sorli, Caroline, Spangenthal, Selwyn, Spence, Niamh, Stephenson, Elaine, Strout, Cynthia, Surowitz, Ronald, Taladua, Kristy Michelle, Tellalian, David, Thalamas, Claire, Thiriphoo, Nang, Thomas, Judith, Thomas, Nicholas, Trout, Guillermo, Urroz, Mikel, Veekmans, Bernard, Veekmans, Laurent, Villalobos, Ralph Elvi M., Warren, Sarah, Webster, Brian, White, Alexander, Williams, Gail, Williams, Hayes, Wilson, Barbara, Winston, Alan, Wiselka, Martin, Zervos, Marcus, Hardt, Karin, Vandebosch, An, Sadoff, Jerald, Le Gars, Mathieu, Truyers, Carla, Lowson, David, Van Dromme, Ilse, Vingerhoets, Johan, Kamphuis, Tobias, Scheper, Gert, Ruiz-Guiñazú, Javier, Faust, Saul N, Spinner, Christoph D, Schuitemaker, Hanneke, Van Hoof, Johan, Douoguih, Macaya, and Struyf, Frank

Published
2022
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9. 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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10. Mitigation strategies to safely conduct HIV treatment research in the context of COVID-19

Author

Henderson, Merle, Mothe, Beatriz, Grinsztejn, Beatriz, Haire, Bridget, Collins, Simon, Lau, Jillian S.Y., Luba, Maureen, Sanne, Ian, Tatoud, Roger, Deeks, Steve, and Lewin, Sharon R.

Subjects
Medical research -- Methods, Medicine, Experimental -- Methods, Epidemics -- Control -- United Kingdom, HIV infection -- Care and treatment -- Research, Health
Abstract

Introduction: The InternationalAIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethicalmanagement of clinicaltrials involving people living with HIV (PLWH) during the SARS-CoV-2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART). Discussion: There is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS-CoV-2 pandemic. How to do this safely and justly remains a criticaldebate. The SARS-CoV-2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS-CoV-2 prevention and treatment strategies, the risk to PLWH in clinicaltrials willdecline over time. However, with the emergence of more contagious and potentially pathogenic SARS-CoV-2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS-CoV-2 prevention and treatment strategies willbe available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research. Conclusions: It can be assumed for the foreseeable future that SARS-CoV-2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop. Keywords: HIV; clinicaltrial; analyticaltreatment interruption (ATI); COVID-19; SARS-CoV-2; risk mitigation, 1 | INTRODUCTION In January 2020, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the causative agent of COVID-19 disease [1]. The World Health [...]

Published
2022
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11. 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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12. 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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13. 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 Jie, Eason, Miles, Castagna, Antonella, Laura, Galli, De Scheerder, Marie‐Angelique, Riley, James, Tebas, Pablo, Gunst, Jesper, Søgaard, Ole, Florence, Eric, Kroon, Eugene, De Souza, Mark, Mothe, Beatriz, Caskey, Marina, and Fidler, Sarah

Abstract

Introduction: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta‐analysis to identify the impact of ATI with or without novel therapeutics in cure‐related studies on the time to viral re‐suppression following ART restart. Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re‐suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI‐only groups. Random‐effects proportional meta‐analysis and multivariable Cox proportional hazards analysis were performed using R. Results: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI‐only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow‐up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40–0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46–0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89–0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59–0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16–2.59). Discussion: When designing studies involving ATIs, information on time to viral re‐suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. Conclusions: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re‐suppression. [ABSTRACT FROM AUTHOR]

Published
2024
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14. 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, HIV/AIDS, Clinical Research, 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. IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV‐infected patients: A retrospective study

Author

Sepúlveda‐Crespo, Daniel, primary, Jiménez‐Sousa, María A., additional, Fernández‐Rodíguez, Amanda, additional, Muñoz‐Fernández, María A., additional, Jiménez, José L., additional, Caraciolo, Begoña B., additional, Reus Bañuls, Sergio, additional, Vilchez, Helem, additional, Mothe, Beatriz, additional, Martínez, Isidoro, additional, Benito, José M., additional, Rallón, Norma, additional, and Resino, Salvador, additional

Published
2023
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19. 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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20. Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 study)

Author

Mothe, Beatriz, Manzardo, Christian, Sanchez-Bernabeu, Alvaro, Coll, Pep, Morón-López, Sara, Puertas, Maria C., Rosas-Umbert, Miriam, Cobarsi, Patricia, Escrig, Roser, Perez-Alvarez, Núria, Ruiz, Irene, Rovira, Cristina, Meulbroek, Michael, Crook, Alison, Borthwick, Nicola, Wee, Edmund G., Yang, Hongbing, Miró, Jose M., Dorrell, Lucy, Clotet, Bonaventura, Martinez-Picado, Javier, Brander, Christian, and Hanke, Tomáš

Published
2019
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21. HLA Alleles, COVID-19 Vaccine Antibody Response and Real-World Breakthrough Outcomes

Author

Prieto-Alhambra, Daniel, primary, Xie, Junqing, additional, Mothe, Beatriz, additional, Herraiz, Marta, additional, Li, Chunxiao, additional, Xu, Yu, additional, Jödicke, Annika, additional, Gao, Yaqing, additional, Feng, Shuo, additional, Wei, Jia, additional, Chen, Zhuoyao, additional, Hong, Shenda, additional, Wu, Yeda, additional, Su, Binbin, additional, Zheng, Xiaoying, additional, Cohet, Catherine, additional, Ali, Raghib, additional, and Wareham, Nicholas, additional

Published
2023
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22. 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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23. 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

24. 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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25. 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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28. 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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29. Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Hardt, Karin, primary, Vandebosch, An, additional, Sadoff, Jerald, additional, Le Gars, Mathieu, additional, Truyers, Carla, additional, Lowson, David, additional, Van Dromme, Ilse, additional, Vingerhoets, Johan, additional, Kamphuis, Tobias, additional, Scheper, Gert, additional, Ruiz-Guiñazú, Javier, additional, Faust, Saul N, additional, Spinner, Christoph D, additional, Schuitemaker, Hanneke, additional, Van Hoof, Johan, additional, Douoguih, Macaya, additional, Struyf, Frank, additional, Garibaldi, Brian T., additional, Albertson, Timothy E., additional, Sandrock, Christian, additional, Lee, Janet S., additional, Looney, Mark R., additional, Tapson, Victor F., additional, Wiysonge, Charles Shey, additional, Velarde, Luis Humberto Anaya, additional, Backenroth, Daniel, additional, Bhushanan, Jisha, additional, Brandenburg, Börries, additional, Cárdenas, Vicky, additional, Chen, Bohang, additional, Chen, Fei, additional, Chetty, Polan, additional, Chu, Pei-Ling, additional, Cooper, Kimberly, additional, Custers, Jerome, additional, Delanghe, Hilde, additional, Duca, Anna, additional, Henrick, Tracy, additional, Juraszek, Jarek, additional, Nalpas, Catherine, additional, Peeters, Monika, additional, Pinheiro, Jose, additional, Roels, Sanne, additional, Ryser, Martin F., additional, Salas, Jose, additional, Santoro Matias, Samantha, additional, Scheys, Ilse, additional, Shetty, Pallavi, additional, Shukarev, Georgi, additional, Stoddard, Jeffrey, additional, Talloen, Willem, additional, Tran, NamPhuong, additional, Vaissiere, Nathalie, additional, van Son-Palmen, Elisabeth, additional, Xu, Jiajun, additional, Goecker, Erin A., additional, Greninger, Alexander L., additional, Jerome, Keith R., additional, Roychoudhury, Pavitra, additional, Takuva, Simbarashe G., additional, Accini Mendoza, Jose Luis, additional, Achtyes, Eric, additional, Ahsan, Habibul, additional, Alhatemi, Azhar, additional, Allen, Nancy, additional, Arribas, Jose R., additional, Bahrami, Ghazaleh, additional, Bailon, Lucia, additional, Bajwa, Ali, additional, Baker, Jonathan, additional, Baron, Mira, additional, Benet, Susana, additional, Berdaï, Driss, additional, Berger, Patrick, additional, Bertoch, Todd, additional, Bethune, Claire, additional, Bevilacqua, Sybille, additional, Biagioni Santos, Maria Silvia, additional, Binnian, Ian, additional, Bisnauthsing, Karen, additional, Boivin, Jean-Marc, additional, Bollen, Hilde, additional, Bonnet, Sandrine, additional, Borobia, Alberto M., additional, Botelho-Nevers, Elisabeth, additional, Bright, Phil, additional, Britten, Vianne, additional, Brown, Claire, additional, Buadi, Amanda, additional, Buntinx, Erik, additional, Burgess, Lesley, additional, Bush, Larry, additional, Capeding, Maria Rosario, additional, Carr, Quito Osuna, additional, Carrasco Mas, Amparo, additional, Catala, Hélène, additional, Cathie, Katrina, additional, Caudill, T. Shawn, additional, Cereto Castro, Fernando, additional, Chau, Kénora, additional, Chavoustie, Steven, additional, Chowdhury, Marie, additional, Chronos, Nicolas, additional, Cicconi, Paola, additional, Cifuentes, Liliana, additional, Cobo, Sara Maria, additional, Collins, Helen, additional, Colton, Hayley, additional, Cuaño, Carlos Rolando G., additional, D'Onofrio, Valentino, additional, Dargan, Paul, additional, Darton, Thomas, additional, Deane, Peter, additional, Del Pozo, Jose Luis, additional, Derdelinckx, Inge, additional, Desai, Amisha, additional, Dever, Michael, additional, Díaz-Pollán, Beatriz, additional, DiBuono, Mark, additional, Doust, Matthew, additional, Duncan, Christopher, additional, Echave-Sustaeta, Jose Maria, additional, Eder, Frank, additional, Ellis, Kimberly, additional, Elzi, Stanton, additional, Emmett, Stevan, additional, Engelbrecht, Johannes, additional, Evans, Mim, additional, Farah, Theo, additional, Felton, Timothy, additional, Ferreira, João Pedro, additional, Floutier, Catherine, additional, Flume, Patrick, additional, Ford, Stacy, additional, Fragoso, Veronica, additional, Freedman, Andrew, additional, Frentiu, Emilia, additional, Galloway, Christopher, additional, Galtier, Florence, additional, Garcia Diaz, Julia, additional, García García, Irene, additional, Garcia, Alcaide, additional, Gardener, Zoe, additional, Gauteul, Pascale, additional, Geller, Steven, additional, Gibson, Andrew, additional, Gillet, Claudia, additional, Girerd, Nicolas, additional, Girodet, Pierre-Olivier, additional, Gler, Maria Tarcela, additional, Glover, Richard, additional, Go, Herschel Don D., additional, Gokani, Karishma, additional, Gonthier, Damien, additional, Green, Christopher, additional, Greenberg, Richard, additional, Griffin, Carl, additional, Grobbelaar, Coert, additional, Guancia, Adonis, additional, Hakkarainen, Gloria, additional, Harris, James, additional, Hassman, Michael, additional, Heimer, Deirdre, additional, Hellstrom-Louw, Elizabeth, additional, Herades, Yoan, additional, Holroyd, Christopher, additional, Hussen, Nazreen, additional, Isidro, Marie Grace Dawn, additional, Jackson, Yvonne, additional, Jain, Manish, additional, João Filho, Esaú Custódio, additional, Johnson, Daniel, additional, Jones, Ben, additional, Joseph, Natasha, additional, Jumeras, Analyn, additional, Junquera, Patricia, additional, Kellett-Wright, Johanna, additional, Kennedy, Patrick, additional, Kilgore, Paul E., additional, Kim, Kenneth, additional, Kimmel, Murray, additional, Konis, George, additional, Kutner, Mark, additional, Lacombe, Karine, additional, Launay, Odile, additional, Lazarus, Rajeka, additional, Lederman, Samuel, additional, Lefebvre, Gigi, additional, Lennon Collins, Katrina, additional, Leroux-Roels, Isabel, additional, Lim, Kenneth Wilson O., additional, Lins, Muriel, additional, Liu, Edward, additional, Llewelyn, Martin, additional, Mahomed, Akbar, additional, Maia, Bernardo Porto, additional, Marín-Candon, Alícia, additional, Martínez-Gómez, Xavier, additional, Martinot, Jean Benoit, additional, Mazzella, Andrea, additional, McCaughan, Frank, additional, McCormack, Louise, additional, McGettigan, John, additional, Mehra, Purvi, additional, Mejeur, Rhonda, additional, Miller, Vicki, additional, Mills, Anthony, additional, Molto Marhuenda, Jose, additional, Moodley, Prebashan, additional, Mora-Rillo, Marta, additional, Mothe, Beatriz, additional, Mullan, Daniel, additional, Munro, Alasdair, additional, Myers, Paul, additional, Nell, Jeremy, additional, Newman Lobato Souza, Tamara, additional, O'Halloran, Jane A., additional, Ochoa Mazarro, Maria Dolores, additional, Oliver, Abigail, additional, Onate Gutierrez, Jose Millan, additional, Ortega, Jessica, additional, Oshita, Masaru, additional, Otero Romero, Susana, additional, Overcash, Jeffrey Scott, additional, Owens, Daniel, additional, Packham, Alice, additional, Pacurar, Mihaela, additional, Paiva de Sousa, Leonardo, additional, Palfreeman, Adrian, additional, Pallares, Christian José, additional, Patel, Rahul, additional, Patel, Suchet, additional, Pelkey, Leslie, additional, Peluso, Denise, additional, Penciu, Florentina, additional, Pinto, S. Jerry, additional, Pounds, Kevin, additional, Pouzar, Joe, additional, Pragalos, Antoinette, additional, Presti, Rachel, additional, Price, David, additional, Qureshi, Ehsaan, additional, Ramalho Madruga, José Valdez, additional, Ramesh, Mayur, additional, Rankin, Bruce, additional, Razat, Béatrice, additional, Riegel Santos, Breno, additional, Riesenberg, Robert, additional, Riffer, Ernie, additional, Roche, Siobhan, additional, Rose, Katie, additional, Rosellini, Pietro, additional, Rossignol, Patrick, additional, Safirstein, Beth, additional, Salazar, Hernan, additional, Sanchez Vallejo, Gregorio, additional, Santhosh, Smrithi, additional, Seco-Meseguer, Enrique, additional, Seep, Michael, additional, Sherry, Emma, additional, Short, Philip, additional, Soentjens, Patrick, additional, Solis, Joel, additional, Soriano Viladomiu, Alejandro, additional, Sorli, Caroline, additional, Spangenthal, Selwyn, additional, Spence, Niamh, additional, Stephenson, Elaine, additional, Strout, Cynthia, additional, Surowitz, Ronald, additional, Taladua, Kristy Michelle, additional, Tellalian, David, additional, Thalamas, Claire, additional, Thiriphoo, Nang, additional, Thomas, Judith, additional, Thomas, Nicholas, additional, Trout, Guillermo, additional, Urroz, Mikel, additional, Veekmans, Bernard, additional, Veekmans, Laurent, additional, Villalobos, Ralph Elvi M., additional, Warren, Sarah, additional, Webster, Brian, additional, White, Alexander, additional, Williams, Gail, additional, Williams, Hayes, additional, Wilson, Barbara, additional, Winston, Alan, additional, Wiselka, Martin, additional, and Zervos, Marcus, additional

Published
2022
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31. 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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32. 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

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

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

Author

Ainsua-Enrich, Erola, primary, Pedreño-Lopez, Nuria, additional, Bracke, Carmen, additional, Avila-Nieto, Carlos, additional, Concepcion, Maria Luisa Rodriguez de la, additional, Pradenas, Edwards, additional, Trinite, Benjamin, additional, Marfil, Silvia, additional, Miranda, Cristina, additional, Gonzalez, Sandra, additional, Toledo, Ruth, additional, Font, Marta, additional, Benet, Susana, additional, Escriba, Tuixent, additional, Jimenez-Moyano, Esther, additional, Peña, Ruth, additional, Cedeño, Samandhy, additional, Prado, Julia G, additional, Mothe, Beatriz, additional, Brander, Christian, additional, Izquierdo-Useros, Nuria, additional, Vergara-Alert, Julia, additional, Segales, Joaquim, additional, Massanella, Marta, additional, Benitez, Rosa Maria, additional, Romero, Alba, additional, Molina-Morata, Daniel, additional, Blanco, Julia, additional, Clotet, Bonaventura, additional, Mateu, Lourdes, additional, Pedro-Botet, Maria Luisa, additional, and Carrillo, Jorge, additional

Published
2022
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36. Epigenetic landscape in the kick-and-kill therapeutic vaccine BCN02 clinical trial is associated with antiretroviral treatment interruption (ATI) outcome

Author

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

Published
2022
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37. Additional file 2 of 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

Abstract

Additional file 1: Supplementary methods. Supplementary results. Figure S1. BCN02-microbiome study design and sample collection strategy. Figure S2. Overview of sample disposition for multi-omic analysis. Figure S3. Taxonomic classification of fecal samples at the order level. Figure S4. Differential abundance in Methanobacteriales between controllers and non-controllers. Figure S5. Linear Discriminant Analysis (LDA) effect size (LEfSe) at the species level. Figure S6. Longitudinal feature-volatility analysis of Bacteroidales and Clostridiales species. Figure S7. Bray-Curtis dissimilarity index between controllers and non-controllers. Figure S8. Gut microbiome profiling excluding B07 participant from non-controllers arm. Figure S9. Differentially abundant metabolic pathways from Bacteroidales and Clostridiales at the study entry. Figure S10. Differential metabolic pathways between controllers and non-controllers. Figure S11. Longitudinal variation of differentially abundant pathways over the trial. Figure S12. Differential archaeal metabolic pathways between controllers and non-controllers. Figure S13. Spearman’s correlation between clinical data, vaccine response and gut microbial variables. Figure S14. Differentially expressed PBMC host genes between controllers and non-controllers at baseline. Figure S15. Protein inflammation markers from controllers and non-controllers at baseline. Figure S16. Functional enrichment of transcripts correlated with the ratio Bacteroidales:Clostridiales and viral reservoir. Figure S17. Integrated analysis of microbiome, metaproteome and transcriptome data.

Published
2022
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38. Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy

Author

Muñoz Moreno, Jose Antonio, Carrillo Molina, Sara, Martínez Zalacaín, Ignacio, Miranda, Cristina, Manzardo, Christian, Coll, Pep, Meulbroek, Michael, Hanke, Tomáš, Garolera, Maite, Miró, Josep M., Brander, Christian, Clotet, Bonaventura, Soriano Mas, Carles, Moltó, José, Mothe, Beatriz, BCN02-Neuro Substudy Group, Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Universitat Oberta de Catalunya. Estudis de Psicologia i Ciències de l'Educació, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Projecte dels NOMS-Hispanosida, Institut de Recerca de la Sida (IrsiCaixa), University of Oxford, Kumamoto University, Consorci Sanitari de Terrassa, Universitat de Vic - Universitat Central de Catalunya, Institució Catalana de Recerca i Estudis Avançats (ICREA), Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona

Subjects
Central Nervous System, Cart, Oncology, infección por VIH, medicine.medical_specialty, estrategias kick & kil, Immunology, Central nervous system, Phases of clinical research, HIV Infections, histone deacetylase inhibitors, inhibidores de histona desacetilasa, HIVconsv, sistema nerviós central, Romidepsin, Neuroimaging, Depsipeptides, Internal medicine, HIV Seropositivity, Clinical endpoint, Humans, Immunology and Allergy, Medicine, kick&kill strategies, romidepsin, business.industry, MVA.HIVconsv, sistema nervioso central, Cognition, estratègies kick&kill, MVA, central nervous system, HIV infection, Histone Deacetylase Inhibitors, Infectious Diseases, medicine.anatomical_structure, Anti-Retroviral Agents, infecció pel VIH, HIV-1, Observational study, romidepsina, business, inhibidors de la histona deacetilasa, medicine.drug
Abstract

Objective: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent. Design: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks. Methods: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6). Results: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints. Conclusion: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.

Published
2022

42. Altered T‐cell subset distribution in the viral reservoir in HIV‐1‐infected individuals with extremely low proviral DNA (LoViReTs)

Author

Gálvez, Cristina, primary, Urrea, Víctor, additional, Garcia‐Guerrero, Maria del Carmen, additional, Bernal, Sílvia, additional, Benet, Susana, additional, Mothe, Beatriz, additional, Bailón, Lucía, additional, Dalmau, Judith, additional, Martinez, Andrea, additional, Nieto, Aroa, additional, Leal, Lorna, additional, García, Felipe, additional, Clotet, Bonaventura, additional, Martinez‐Picado, Javier, additional, and Salgado, Maria, additional

Published
2022
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43. Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1

Author

Mothe, Beatriz, Climent, Nuria, Plana, Montserrat, Rosàs, Miriam, Jiménez, José Luis, Muñoz-Fernández, María Ángeles, Puertas, María C., Carrillo, Jorge, Gonzalez, Nuria, León, Agathe, Pich, Judit, Arnaiz, Joan Albert, Gatell, Jose M., Clotet, Bonaventura, Blanco, Julià, Alcamí, José, Martinez-Picado, Javier, Alvarez-Fernández, Carmen, Sánchez-Palomino, Sonsoles, Guardo, Alberto C., Peña, José, Benito, José M., Rallón, Norma, Gómez, Carmen E., Perdiguero, Beatriz, García-Arriaza, Juan, Esteban, Mariano, López Bernaldo de Quirós, Juan Carlos, Brander, Christian, García, Felipe, Mothe, Beatriz, Cobarsi, Patricia, Rosàs, Miriam, Puertas, María C., Carrillo, Jorge, Blanco, Juliá, Martinez-Picado, Javier, Clotet, Bonaventura, Brander, Christian, Climent, Nuria, Plana, Montserrat, Alvarez, Carmen, Sánchez, Sonsoles, León, Agathe, Pich, Judit, Arnaiz, Joan Albert, Leal, Lorna, Torres, Berta, Lucero, Constanza, Guardo, Alberto C., Gatell, Jose M., García, Felipe, Jiménez, José Luis, Muñoz-Fernández, María Angeles, López Bernaldo de Quirós, Juan Carlos, Esteban, Mariano, Gómez, Carmen Elena, Perdiguero, Beatriz, García-Arriaza, Juan, Cepeda, Victoria, Sánchez-Sorzano, Carlos Oscar, Gonzalez, Nuria, Alcamí, José, Jiménez, Laura, Benito, José M., Rallón, Norma, and Peña, José

Published
2015
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44. 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, Mothe, Beatriz, Barriocanal, Ana María, Benet, Susana, Cobarsi, Patricia, Geleziunas, Romas, Loste, Cora, Meulbroek, Michael, Miranda, Cristina, Muñoz, Jose, Naval, Jordi, Nieto, Aroa, Pujol, Ferran, and Puig, Jordi

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml−1, >10,000 copies ml−1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

Published
2021

46. Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy

Author

Muñoz-Moreno, Jose A., primary, Carrillo-Molina, Sara, additional, Martínez-Zalacaín, Ignacio, additional, Miranda, Cristina, additional, Manzardo, Christian, additional, Coll, Pep, additional, Meulbroek, Michael, additional, Hanke, Tomáš, additional, Garolera, Maite, additional, Miró, Josep M., additional, Brander, Christian, additional, Clotet, Bonaventura, additional, Soriano-Mas, Carles, additional, Moltó, José, additional, and Mothe, Beatriz, additional

Published
2021
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48. 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, and Caskey, Marina

Subjects
CELLULAR immunity, IMMUNITY, IMMUNOGLOBULINS, INFECTION prevention, MONOCLONAL antibodies, HIV
Abstract

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control. Broadly neutralising anti-HIV-1 antibody (bNAb) administration in nonhuman primates has been shown to stimulate adaptive T cell-specific immunity, with infection prevention observed. In this work, the authors longitudinally analyse HIV-1 specific cellular immunity in HIV-1- infected individuals starting ART with or without adjunctive bNAb treatment. [ABSTRACT FROM AUTHOR]

Published
2022
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