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1. Author Correction: Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, Pedro J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Núria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, and Gómez, Carmen Elena

Published
2024
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2. Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, Pedro J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Núria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, and Gómez, Carmen Elena

Published
2024
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4. Correction for Kibler et al., “Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC”

Author

Kibler, Karen V, Asbach, Benedikt, Perdiguero, Beatriz, García-Arriaza, Juan, Yates, Nicole L, Parks, Robert, Stanfield-Oakley, Sherry, Ferrari, Guido, Montefiori, David C, Tomaras, Georgia D, Roederer, Mario, Foulds, Kathryn E, Forthal, Donald N, Seaman, Michael S, Self, Steve, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan, Cristillo, Anthony D, Weiss, Deborah, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Esteban, Mariano, Wagner, Ralf, Pantaleo, Giuseppe, and Jacobs, Bertram L

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Good Health and Well Being, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Volume 93, no. 3, e01513-18, 2019, https://doi.org/10.1128/JVI.01513-18. The article was originally published on 17 January 2019 with a standard copyright line (“© 2019 American Society for Microbiology. All Rights Reserved.”). We elected to pay for open access for the article after publication, necessitating replacement of the original copyright line with “© 2019 Kibler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.” This change was made to the online version of the article on 21 August 2019.

Published
2019

6. Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.

Author

Kibler, Karen V, Asbach, Benedikt, Perdiguero, Beatriz, García-Arriaza, Juan, Yates, Nicole L, Parks, Robert, Stanfield-Oakley, Sherry, Ferrari, Guido, Montefiori, David C, Tomaras, Georgia D, Roederer, Mario, Foulds, Kathryn E, Forthal, Donald N, Seaman, Michael S, Self, Steve, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan, Cristillo, Anthony D, Weiss, Deborah, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Esteban, Mariano, Wagner, Ralf, Pantaleo, Giuseppe, and Jacobs, Bertram L

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related (AIDS), Biotechnology, Prevention, Immunization, HIV/AIDS, Vaccine Related, Infectious Diseases, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, Animals, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, HIV Antibodies, HIV Antigens, HIV Infections, HIV-1, Humans, Macaca mulatta, Male, Vaccination, Vaccinia virus, Viral Vaccines, Virus Replication, env Gene Products, Human Immunodeficiency Virus, Gag-Pol-Nef, HIV, NYVAC, NYVAC-KC, T cell response, antibody responses, gp140, nonhuman primates, vaccines, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.

Published
2019

7. Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost.

Author

Asbach, Benedikt, Kibler, Karen V, Köstler, Josef, Perdiguero, Beatriz, Yates, Nicole L, Stanfield-Oakley, Sherry, Tomaras, Georgia D, Kao, Shing-Fen, Foulds, Kathryn E, Roederer, Mario, Seaman, Michael S, Montefiori, David C, Parks, Robert, Ferrari, Guido, Forthal, Donald N, Phogat, Sanjay, Tartaglia, James, Barnett, Susan W, Self, Steven G, Gottardo, Raphael, Cristillo, Anthony D, Weiss, Deborah E, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Esteban, Mariano, Jacobs, Bertram L, Pantaleo, Giuseppe, and Wagner, Ralf

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, Vaccine Related, HIV/AIDS, Biotechnology, Immunization, Rare Diseases, Vaccine Related (AIDS), Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, Animals, Antibodies, Neutralizing, HIV Antibodies, HIV Antigens, HIV Infections, HIV-1, Humans, Macaca mulatta, Male, Poxviridae, T-Lymphocytes, Vaccination, Vaccines, DNA, Vaccinia virus, Viral Vaccines, Virus Replication, DNA vaccine, Gag-Pol-Nef, NYVAC, NYVAC-KC, T cell responses, antibody responses, gp140, human immunodeficiency virus, nonhuman primates, vaccine, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

Published
2019

8. Potency and durability of T and B cell immune responses after homologous and heterologous vector delivery of a trimer-stabilized, membrane-displayed HIV-1 clade ConC Env protein

Author

Perdiguero, Beatriz, primary, Hauser, Alexandra, additional, Gómez, Carmen Elena, additional, Peterhoff, David, additional, Sideris, Elefthéria, additional, Sorzano, Carlos Óscar S., additional, Wilmschen, Sarah, additional, Schaber, Marion, additional, Stengel, Laura, additional, Asbach, Benedikt, additional, Ding, Song, additional, Von Laer, Dorothee, additional, Levy, Yves, additional, Pantaleo, Giuseppe, additional, Kimpel, Janine, additional, Esteban, Mariano, additional, and Wagner, Ralf, additional

Published
2023
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9. Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

Author

Asbach, Benedikt, Kliche, Alexander, Köstler, Josef, Perdiguero, Beatriz, Esteban, Mariano, Jacobs, Bertram L, Montefiori, David C, LaBranche, Celia C, Yates, Nicole L, Tomaras, Georgia D, Ferrari, Guido, Foulds, Kathryn E, Roederer, Mario, Landucci, Gary, Forthal, Donald N, Seaman, Michael S, Hawkins, Natalie, Self, Steven G, Sato, Alicia, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan W, Burke, Brian, Cristillo, Anthony D, Weiss, Deborah E, Francis, Jesse, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Pantaleo, Giuseppe, Wagner, Ralf, and Silvestri, G.

Published
2016

10. Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

Author

Perdiguero, Beatriz, primary, Marcos-Villar, Laura, additional, López-Bravo, María, additional, Sánchez-Cordón, Pedro J., additional, Zamora, Carmen, additional, Valverde, José Ramón, additional, Sorzano, Carlos Óscar S., additional, Sin, Laura, additional, Álvarez, Enrique, additional, Ramos, Manuel, additional, Del Val, Margarita, additional, Esteban, Mariano, additional, and Gómez, Carmen Elena, additional

Published
2023
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11. An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses

Author

Falqui, Michela, primary, Perdiguero, Beatriz, additional, Coloma, Rocio, additional, Albert, Manuel, additional, Marcos-Villar, Laura, additional, McGrail, Joseph Patrick, additional, Sorzano, Carlos Óscar S., additional, Esteban, Mariano, additional, Gómez, Carmen Elena, additional, and Guerra, Susana, additional

Published
2023
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13. The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses

Author

Usero, Lorena, primary, Leal, Lorna, additional, Gómez, Carmen Elena, additional, Miralles, Laia, additional, Aurrecoechea, Elena, additional, Esteban, Ignasi, additional, Torres, Berta, additional, Inciarte, Alexy, additional, Perdiguero, Beatriz, additional, Esteban, Mariano, additional, García, Felipe, additional, and Plana, Montserrat, additional

Published
2023
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15. Early and Long-Term HIV-1 Immunogenicity Induced in Macaques by the Combined Administration of DNA, NYVAC and Env Protein-Based Vaccine Candidates: The AUP512 Study

Author

Perdiguero, Beatriz, primary, Asbach, Benedikt, additional, Gómez, Carmen E., additional, Köstler, Josef, additional, Barnett, Susan W., additional, Koutsoukos, Marguerite, additional, Weiss, Deborah E., additional, Cristillo, Anthony D., additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Montefiori, David C., additional, Yates, Nicole L., additional, Ferrari, Guido, additional, Shen, Xiaoying, additional, Sawant, Sheetal, additional, Tomaras, Georgia D., additional, Sato, Alicia, additional, Fulp, William J., additional, Gottardo, Raphael, additional, Ding, Song, additional, Heeney, Jonathan L., additional, Pantaleo, Giuseppe, additional, Esteban, Mariano, additional, and Wagner, Ralf, additional

Published
2022
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17. 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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18. Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen

Author

Gómez, Carmen Elena, primary, Perdiguero, Beatriz, additional, Usero, Lorena, additional, Marcos-Villar, Laura, additional, Miralles, Laia, additional, Leal, Lorna, additional, Sorzano, Carlos Óscar S., additional, Sánchez-Corzo, Cristina, additional, Plana, Montserrat, additional, García, Felipe, additional, and Esteban, Mariano, additional

Published
2021
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23. Heterologous Combination of VSV-GP and NYVAC Vectors Expressing HIV-1 Trimeric gp145 Env as Vaccination Strategy to Induce Balanced B and T Cell Immune Responses

Author

Perdiguero, Beatriz, primary, Gómez, Carmen Elena, additional, García-Arriaza, Juan, additional, Sánchez-Corzo, Cristina, additional, Sorzano, Carlos Óscar S., additional, Wilmschen, Sarah, additional, von Laer, Dorothee, additional, Asbach, Benedikt, additional, Schmalzl, Christina, additional, Peterhoff, David, additional, Ding, Song, additional, Wagner, Ralf, additional, Kimpel, Janine, additional, Levy, Yves, additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2019
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24. The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1

Author

Raman, Suresh C., primary, Mejías-Pérez, Ernesto, additional, Gomez, Carmen E., additional, García-Arriaza, Juan, additional, Perdiguero, Beatriz, additional, Vijayan, Aneesh, additional, Pérez-Ruiz, Mar, additional, Cuervo, Ana, additional, Santiago, César, additional, Sorzano, Carlos Oscar S., additional, Sánchez-Corzo, Cristina, additional, Moog, Christiane, additional, Burger, Judith A., additional, Schorcht, Anna, additional, Sanders, Rogier W., additional, Carrascosa, José L., additional, and Esteban, Mariano, additional

Published
2019
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26. A Novel MVA-Based HIV Vaccine Candidate (MVA-gp145-GPN) Co-Expressing Clade C Membrane-Bound Trimeric gp145 Env and Gag-Induced Virus-Like Particles (VLPs) Triggered Broad and Multifunctional HIV-1-Specific T Cell and Antibody Responses

Author

Perdiguero, Beatriz, primary, Sánchez-Corzo, Cristina, additional, Sorzano, Carlos, additional, Saiz, Lidia, additional, Mediavilla, Pilar, additional, Esteban, Mariano, additional, and Gómez, Carmen, additional

Published
2019
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28. Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant.

Author

Elena Gómez, Carmen, Perdiguero, Beatriz, Falqui, Michela, Marín, María Q., Bécares, Martina, Sorzano, Carlos Óscar S., García-Arriaza, Juan, Esteban, Mariano, and Guerra, Susana

Subjects
*T cells, *INTERFERON gamma, *POST-translational modification, *HIV, *VACCINIA, *VIRUS diseases
Abstract

Induction of the endogenous innate immune system by interferon (IFN) triggers the expression of many proteins that serve like alarm bells in the body, activating an immune response. After a viral infection, one of the genes activated by IFN induction is the IFN-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein that undergoes a reversible posttranslational modification (ISGylation). ISG15 protein can also act unconjugated, intracellularly and secreted, acting as a cytokine. Although ISG15 has an essential role in host defense responses to microbial infection, its role as an immunomodulator in the vaccine field remains to be defined. In this investigation, we showed that ISG15 exerts an immunomodulatory role in human immunodeficiency virus (HIV) vaccines. In mice, after priming with a DNA-ISG15 vector mixed with a DNA expressing HIV-1 gp120 (DNA-gp120), followed by a booster with a modified vaccinia virus Ankara (MVA) vector expressing HIV-1 antigens, both wild-type ISG15-conjugated (ISG15-wt) and mutant unconjugated (ISG15-mut) proteins act as immune adjuvants by increasing the magnitude and quality of HIV-1-specific CD8 T cells, with ISG15-wt providing better immunostimulatory activity than ISG15-mut. The HIV-1 Env-specific CD8 T cell responses showed a predominant T effector memory (TEM) phenotype in all groups. Moreover, the amount of DNAgp120 used to immunize mice could be reduced 5-fold after mixing with DNA-ISG15 without affecting the potency and the quality of the HIV-1 Env-specific immune responses. Our study clearly highlights the potential use of the IFN-induced ISG15 protein as immune adjuvant to enhance immune responses to HIV antigens, suggesting that this molecule might be exploitable for prophylactic and therapeutic vaccine approaches against pathogens. [ABSTRACT FROM AUTHOR]

Published
2021
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29. Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization

Author

Crespo Guardo, Alberto, Gómez, Carmen Elena, Díaz Brito, Vicens, Pich, Judit, Arnaiz Gargallo, Juan Alberto, Perdiguero, Beatriz, García Arriaza, Juan, GonzÁlez, Núria, Sorzano, Carlos O. S., Jiménez, Laura, Jiménez, José Luis, Muñoz Fernández, María Ángeles, Gatell, José M., Alcamí, José, Esteban, Mariano, López Bernaldo de Quirós, Juan Carlos, García Alcaide, Felipe, Plana Prades, Montserrat, RISVAC02boost study, Instituto de Salud Carlos III, and Institut d’Investigacions Biomédiques August Pi I Sunyer

Subjects
0301 basic medicine, RNA viruses, CD4-Positive T-Lymphocytes, Physiology, viruses, Human immunodeficiency virus (HIV), lcsh:Medicine, Antibody Response, CD8-Positive T-Lymphocytes, HIV Antibodies, medicine.disease_cause, Pathology and Laboratory Medicine, Biochemistry, Placebos, White Blood Cells, Immunodeficiency Viruses, Animal Cells, Immune Physiology, Healthy volunteers, Medicine and Health Sciences, Medicine, Public and Occupational Health, Enzyme-Linked Immunoassays, Sida, lcsh:Science, Immune Response, AIDS Vaccines, Multidisciplinary, Immune System Proteins, biology, T Cells, MVA-B, Flow Cytometry, Vaccination and Immunization, Healthy Volunteers, Cèl·lules T, Medical Microbiology, Viral Pathogens, Viruses, Cellular Types, Pathogens, Research Article, Immune Cells, Immunology, T cells, Immunization, Secondary, Cytotoxic T cells, Enzyme-Linked Immunosorbent Assay, Research and Analysis Methods, complex mixtures, Microbiology, Antibodies, 03 medical and health sciences, Immune system, Vacunes antivíriques, Retroviruses, VIH (Virus), Humans, Immunoassays, Microbial Pathogens, Blood Cells, business.industry, HIV (Viruses), Viral vaccines, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, Proteins, HIV, Correction, Cell Biology, biology.organism_classification, Virology, Antibodies, Neutralizing, 030104 developmental biology, Immunization, Immunologic Techniques, HIV-1, lcsh:Q, Preventive Medicine, business
Abstract

BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. RESULTS: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. CONCLUSIONS: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923610. This study was partially supported by grants: FIS PI12/00969, PI15/00480, SAF2015-66193-R., EC10-153, TRA-094, RIS, HIVACAT, SAF2013-45232-R. RIS: Red Temática Cooperativa de Grupos de Investigación en Sida del Fondo de Investigación Sanitaria (FIS). HIVACAT: HIV development program in Catalonia. IDIBAPS: Institut d’Investigacions Biomèdiques August Pi I Sunyer. Sí

Published
2016

30. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates

Author

Saunders, Kevin O., primary, Santra, Sampa, additional, Parks, Robert, additional, Yates, Nicole L., additional, Sutherland, Laura L., additional, Scearce, Richard M., additional, Balachandran, Harikrishnan, additional, Bradley, Todd, additional, Goodman, Derrick, additional, Eaton, Amanda, additional, Stanfield-Oakley, Sherry A., additional, Tartaglia, James, additional, Phogat, Sanjay, additional, Pantaleo, Giuseppe, additional, Esteban, Mariano, additional, Gomez, Carmen E., additional, Perdiguero, Beatriz, additional, Jacobs, Bertram, additional, Kibler, Karen, additional, Korber, Bette, additional, Montefiori, David C., additional, Ferrari, Guido, additional, Vandergrift, Nathan, additional, Liao, Hua-Xin, additional, Tomaras, Georgia D., additional, and Haynes, Barton F., additional

Published
2018
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32. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates

Author

García-Arriaza, Juan, primary, Perdiguero, Beatriz, additional, Heeney, Jonathan L., additional, Seaman, Michael S., additional, Montefiori, David C., additional, Yates, Nicole L., additional, Tomaras, Georgia D., additional, Ferrari, Guido, additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Self, Steven G., additional, Borate, Bhavesh, additional, Gottardo, Raphael, additional, Phogat, Sanjay, additional, Tartaglia, Jim, additional, Barnett, Susan W., additional, Burke, Brian, additional, Cristillo, Anthony D., additional, Weiss, Deborah E., additional, Lee, Carter, additional, Kibler, Karen V., additional, Jacobs, Bertram L., additional, Wagner, Ralf, additional, Ding, Song, additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2017
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33. Proceedings of the Frontiers of Retrovirology Conference 2016

Author

Zurnic, Irena, primary, Hütter, Sylvia, additional, Lehmann, Ute, additional, Stanke, Nicole, additional, Reh, Juliane, additional, Kern, Tobias, additional, Lindel, Fabian, additional, Gerresheim, Gesche, additional, Hamann, Martin, additional, Müllers, Erik, additional, Lesbats, Paul, additional, Cherepanov, Peter, additional, Serrao, Erik, additional, Engelman, Alan, additional, Lindemann, Dirk, additional, Da Silva Santos, Claire, additional, Tartour, Kevin, additional, Cimarelli, Andrea, additional, Burdick, Rya, additional, Chen, Jianbo, additional, Sastri, Jaya, additional, Hu, Wei-Shau, additional, Pathak, Vinay, additional, Keppler, Oliver T., additional, Pradeau, Karine, additional, Eiler, Sylvia, additional, Levy, Nicolas, additional, Lennon, Sarah, additional, Cianferani, Sarah, additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Parissi, Vincent, additional, Rato, Sylvie, additional, Rausell, Antonio, additional, Munoz, Miguel, additional, Telenti, Amalio, additional, Ciuffi, Angela, additional, Zhyvoloup, Alexander, additional, Melamed, Anat, additional, Anderson, Ian, additional, Planas, Delphine, additional, Kriston-Vizi, Janos, additional, Ketteler, Robin, additional, Lee, Chen- Hsuin, additional, Merritt, Andy, additional, Ancuta, Petronela, additional, Bangham, Charles, additional, Fassati, Ariberto, additional, Rodari, Anthony, additional, Van Driessche, Benoit, additional, Galais, Mathilde, additional, Delacourt, Nadége, additional, Fauquenoy, Sylvain, additional, Vanhulle, Caroline, additional, Kula, Anna, additional, Burny, Arsène, additional, Rohr, Olivier, additional, Van Lint, Carine, additional, van Montfort, Thijs, additional, van der Sluis, Renee, additional, Speijer, Dave, additional, Berkhout, Ben, additional, Meng, Bo, additional, Rutkowski, Andrzej, additional, Berry, Neil, additional, Dölken, Lars, additional, Lever, Andrew, additional, Schuster, Thomas, additional, Asbach, Benedikt, additional, Wagner, Ralf, additional, Gross, Christine, additional, Wiesmann, Veit, additional, Kalmer, Martina, additional, Wittenberg, Thomas, additional, Gettemans, Jan, additional, Thoma-Kress, Andrea K., additional, Li, Minghua, additional, Freed, Eric O., additional, Liu, Shan-Lu, additional, Müller, Janis, additional, Münch, Jan, additional, Sewald, Xaver, additional, Uchil, Pradeep, additional, Ladinsky, Mark, additional, Beloor, Jagadish, additional, Pi, Ruoxi, additional, Herrmann, Christin, additional, Motamedi, Nasim, additional, Murooka, Thomas, additional, Brehm, Michael, additional, Greiner, Dale, additional, Mempel, Thorsten, additional, Bjorkman, Pamela, additional, Kumar, Priti, additional, Mothes, Walther, additional, Joas, Simone, additional, Parrish, Erica, additional, Gnanadurai, Clement Wesley, additional, Lump, Edina, additional, Stürzel, Christina M., additional, Parrish, Nicholas F., additional, Sauermann, Ulrike, additional, Töpfer, Katharina, additional, Schultheiss, Tina, additional, Bosinger, Steven, additional, Silvestri, Guido, additional, Apetrei, Cristian, additional, Huot, Nicholas, additional, Müller-Trutwin, Michaela, additional, Sauter, Daniel, additional, Hahn, Beatrice H., additional, Stahl-Hennig, Christiane, additional, Kirchhoff, Frank, additional, Schumann, Gerald, additional, Jung-Klawitter, Sabine, additional, Fuchs, Nina V., additional, Upton, Kyle R., additional, Muñoz-Lopez, Martin, additional, Shukla, Ruchi, additional, Wang, Jichang, additional, Garcia-Canadas, Marta, additional, Lopez-Ruiz, Cesar, additional, Gerhardt, Daniel J., additional, Sebe, Attila, additional, Grabundzija, Ivana, additional, Gerdes, Patricia, additional, Merkert, Sylvia, additional, Pulgarin, Andres, additional, Bock, Anja, additional, Held, Ulrike, additional, Witthuhn, Anett, additional, Haase, Alexandra, additional, Wolvetang, Ernst J., additional, Martin, Ulrich, additional, Ivics, Zoltán, additional, Izsvák, Zsuzsanna, additional, Garcia-Perez, J., additional, Faulkner, Geoffrey J., additional, Hurst, Tara, additional, Katzourakis, Aris, additional, Magiorkinis, Gkikas, additional, Schott, Kerstin, additional, Derua, Rita, additional, Seifried, Janna, additional, Reuter, Andreas, additional, Schmitz, Heike, additional, Tondera, Christiane, additional, Brandariz-Nuñez, Alberto, additional, Diaz-Griffero, Felipe, additional, Janssens, Veerle, additional, König, Renate, additional, Baldauf, Hanna-Mari, additional, Stegmann, Lena, additional, Schwarz, Sarah-Marie, additional, Trotard, Maud, additional, Martin, Margarethe, additional, Lenzi, Gina, additional, Burggraf, Manja, additional, Pan, Xiaoyu, additional, Fregoso, Oliver I., additional, Lim, Efrem S., additional, Abraham, Libin, additional, Erikson, Elina, additional, Nguyen, Laura, additional, Ambiel, Ina, additional, Rutsch, Frank, additional, Kim, Baek, additional, Emerman, Michael, additional, Fackler, Oliver T., additional, Wittmann, Sabine, additional, Behrendt, Rayk, additional, Volkmann, Bianca, additional, Eissmann, Kristin, additional, Gramberg, Thomas, additional, Bolduan, Sebastian, additional, Koppensteiner, Herwig, additional, Regensburg, Stefanie, additional, Brack-Werner, Ruth, additional, Draenert, Rika, additional, Schindler, Michael, additional, Ducroux, Aurélie, additional, Xu, Shuting, additional, Ponnurangam, Aparna, additional, Franz, Sergej, additional, Malassa, Angelina, additional, Ewald, Ellen, additional, Goffinet, Christine, additional, Fung, Sin-Yee, additional, Chan, Ching-Ping, additional, Yuen, Chun-Kit, additional, Kok, Kin-Hang, additional, Chan, Chin-Ping, additional, Jin, Dong-Yan, additional, Dittmer, Ulf, additional, Kmiec, Dorota, additional, Iyer, Shilpa, additional, Stürzel, Christina, additional, Hahn, Beatrice, additional, Ariumi, Yasuo, additional, Yasuda-Inoue, Mariko, additional, Kawano, Koudai, additional, Tateishi, Satoshi, additional, Turelli, Priscilla, additional, Compton, Alex, additional, Roy, Nicolas, additional, Porrot, Françoise, additional, Billet, Anne, additional, Casartelli, Nicoletta, additional, Yount, Jacob, additional, Liang, Chen, additional, Schwartz, Oliver, additional, Magnus, Carsten, additional, Reh, Lucia, additional, Moore, Penny, additional, Uhr, Therese, additional, Weber, Jacqueline, additional, Morris, Lynn, additional, Trkola, Alexandra, additional, Grindberg, Rashel V., additional, Schlaepfer, Erika, additional, Schreiber, Gideon, additional, Simon, Viviana, additional, Speck, Roberto F., additional, Debyser, Zeger, additional, Vranckx, Lenard, additional, Demeulemeester, Jonas, additional, Saleh, Suha, additional, Verdin, Eric, additional, Cereseto, Anna, additional, Christ, Frauke, additional, Gijsbers, Rik, additional, Wang, Gang, additional, Zhao, Na, additional, Das, Atze T., additional, Köstler, Josef, additional, Perdiguero, Beatriz, additional, Esteban, Mariano, additional, Jacobs, Bertram L., additional, Montefiori, David C., additional, LaBranche, Celia C., additional, Yates, Nicole L., additional, Tomaras, Georgia D., additional, Ferrari, Guido, additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Landucci, Gary, additional, Forthal, Donald N., additional, Seaman, Michael S., additional, Hawkins, Natalie, additional, Self, Steven G., additional, Phogat, Sanjay, additional, Tartaglia, James, additional, Barnett, Susan W., additional, Burke, Brian, additional, Cristillo, Anthony D., additional, Ding, Song, additional, Heeney, Jonathan L., additional, Pantaleo, Giuseppe, additional, Stab, Viktoria, additional, Ensser, Armin, additional, Tippler, Bettina, additional, Burton, Dennis, additional, Tenbusch, Matthias, additional, Überla, Klaus, additional, Alter, Galit, additional, Lofano, Giuseppe, additional, Dugast, Anne-Sophie, additional, Kulkarni, Viraj, additional, Suscovich, Todd, additional, Opazo, Tatiana, additional, Barraza, Felipe, additional, Herrera, Diego, additional, Garces, Andrea, additional, Schwenke, Tomas, additional, Tapia, Diego, additional, Cancino, Jorge, additional, Arriagada, Gloria, additional, Haußner, Christina, additional, Damm, Dominik, additional, Rohrhofer, Anette, additional, Schmidt, Barbara, additional, Eichler, Jutta, additional, Midgley, Rebecca, additional, Wheeldon, James, additional, Piguet, Vincent, additional, Khopkar, Priyanka, additional, Rohamare, Megha, additional, Kulkarni, Smita, additional, Godinho-Santos, Ana, additional, Hance, Allan, additional, Goncalves, Joao, additional, Mammano, Fabrizio, additional, Gasser, Romain, additional, Hamoudi, Meriem, additional, Pellicciotta, Martina, additional, Zhou, Zhicheng, additional, Visdeloup, Clara, additional, Colin, Philippe, additional, Braibant, Martine, additional, Lagane, Bernard, additional, Negroni, Matteo, additional, Wamara, Jula, additional, Bannert, Norbert, additional, Mesplede, Thibault, additional, Osman, Nathan, additional, Anstett, Kaitlin, additional, Liang, Jiaming Calvin, additional, Pham, Hanh Thi, additional, Wainberg, Mark, additional, Shao, Wei, additional, Shan, Jigui, additional, Kearney, Mary, additional, Wu, Xiaolin, additional, Maldarelli, Frank, additional, Mellors, John, additional, Luke, Brian, additional, Coffin, John, additional, Hughes, Stephen, additional, Fricke, Thomas, additional, Opp, Silvana, additional, Shepard, Caitlin, additional, Ivanov, Dmitri, additional, Valle-Casuso, Jose, additional, Kanja, Marine, additional, Cappy, Pierre, additional, Lener, Daniela, additional, Knyazhanskaya, Ekaterina, additional, Anisenko, Andrey, additional, Zatsepin, Timofey, additional, Gottikh, Marina, additional, Komkov, Alexander, additional, Minervina, Anastasia, additional, Nugmanov, Gaiaz, additional, Nazarov, Vadim, additional, Khodosevich, Konstantin, additional, Mamedov, Ilgar, additional, Lebedev, Yuri, additional, Colomer-Lluch, Marta, additional, Serra-Moreno, Ruth, additional, Sarracino, Ambra, additional, Gharu, Lavina, additional, Pasternak, Alexander, additional, Marcello, Alessandro, additional, McCartin, Ann Marie, additional, Kulkarni, Anurag, additional, Le Douce, Valentin, additional, Gautier, Virginie, additional, Baeyens, Ann, additional, Naessens, Evelien, additional, Van Nuffel, Anouk, additional, Weening, Karin, additional, Reilly, Anne- Marie, additional, Claeys, Eva, additional, Trypsteen, Wim, additional, Vandekerckhove, Linos, additional, Eyckerman, Sven, additional, Gevaert, Kris, additional, Verhasselt, Bruno, additional, Mok, Hoi Ping, additional, Norton, Nicholas, additional, Fun, Axel, additional, Hirst, Jack, additional, Wills, Mark, additional, Miklik, Dalibor, additional, Senigl, Filip, additional, Hejnar, Jiri, additional, Sakuragi, Jun-ichi, additional, Sakuragi, Sayuri, additional, Yokoyama, Masaru, additional, Shioda, Tatsuo, additional, Sato, Hironori, additional, Bodem, Jochen, additional, Moschall, Rebecca, additional, Denk, Sarah, additional, Erkelenz, Steffen, additional, Schenk, Christian, additional, Schaal, Heiner, additional, Donhauser, Norbert, additional, Socher, Ellen, additional, Millen, Sebastian, additional, Sticht, Heinrich, additional, Mann, Melanie, additional, Wei, Guochao, additional, Betts, Matthew J., additional, Liu, Yang, additional, Kehl, Timo, additional, Russell, Robert B., additional, Löchelt, Martin, additional, Hohn, Oliver, additional, Mostafa, Saeed, additional, Hanke, Kirsten, additional, Norley, Stephen, additional, Chen, Chia-Yen, additional, Shingai, Masashi, additional, Borrego, Pedro, additional, Taveira, Nuno, additional, Strebel, Klaus, additional, Hellmund, Chris, additional, Friedrich, Melanie, additional, Hahn, Friedrich, additional, Setz, Christian, additional, Rauch, Pia, additional, Fraedrich, Kirsten, additional, Matthaei, Alina, additional, Henklein, Petra, additional, Traxdorf, Maximilian, additional, Fossen, Torgils, additional, Schubert, Ulrich, additional, Khwaja, Aya, additional, Galilee, Meytal, additional, Alian, Akram, additional, Schwalbe, Birco, additional, Hauser, Heiko, additional, Schreiber, Michael, additional, Scherpenisse, Mirte, additional, Cho, Young-Keol, additional, Kim, Jungeun, additional, Jeong, Daeun, additional, Trejbalova, Katerina, additional, Benesova, Martina, additional, Kucerova, Dana, additional, Vernerova, Zdenka, additional, Amouroux, Rachel, additional, Hajkova, Petra, additional, Elleder, Daniel, additional, Hron, Tomas, additional, Farkasova, Helena, additional, Padhi, Abinash, additional, Paces, Jan, additional, Zhu, Henan, additional, Gifford, Robert, additional, Murcia, Pablo, additional, Carrozza, Maria Luisa, additional, Niewiadomska, Anna-Maria, additional, Mazzei, Maurizio, additional, Abi-Said, Mounir, additional, Hughes, Joseph, additional, Hué, Stéphane, additional, Obasa, Adetayo, additional, Jacobs, Graeme, additional, Engelbrecht, Susan, additional, Mack, Katharina, additional, Starz, Kathrin, additional, Geyer, Matthias, additional, Bibollet-Ruche, Frederic, additional, Leoz, Marie, additional, Plantier, Jean Christophe, additional, Argaw-Denboba, Ayele, additional, Balestrieri, Emanuela, additional, Serafino, Annalucia, additional, Bucci, Ilaria, additional, Cipriani, Chiara, additional, Spadafora, Corrado, additional, Sinibaldi-Vallebona, Paolo, additional, Matteucci, Claudia, additional, Jayashree, S. Nandi, additional, Neogi, Ujjwal, additional, Chhangani, Anil K., additional, Rathore, Shravan Sing, additional, Mathur, Bajrang R. J., additional, Abati, Adeyemi, additional, Koç, B. Taylan, additional, Oğuzoğlu, Tuba Çiğdem, additional, Shimauchi, Takatoshi, additional, Caucheteux, Stephan, additional, Turpin, Jocelyn, additional, Finsterbusch, Katja, additional, Tokura, Yoshiki, additional, Souriant, Shanti, additional, Balboa, Luciana, additional, Pingris, Karine, additional, Kviatcowsky, Denise, additional, Raynaud-Messina, Brigitte, additional, Cougoule, Céline, additional, Mercier, Ingrid, additional, Kuroda, Marcelo, additional, González-Montaner, Pablo, additional, Inwentarz, Sandra, additional, Moraña, Eduardo Jose, additional, del Carmen Sasiain, Maria, additional, Neyrolles, Olivier, additional, Maridonneau-Parini, Isabelle, additional, Lugo-Villarino, Geanncarlo, additional, Vérollet, Christel, additional, Herrmann, Alexandra, additional, Thomas, Dominique, additional, Bouzas, Nerea Ferreirós, additional, Lahaye, Xavier, additional, Bhargava, Anvita, additional, Satoh, Takeshi, additional, Gentili, Matteo, additional, Cerboni, Silvia, additional, Silvin, Aymeric, additional, Conrad, Cécile, additional, Ahmed-Belkacem, Hakim, additional, Rodriguez, Elisa C., additional, Guichou, Jean-François, additional, Bosquet, Nathalie, additional, Piel, Matthieu, additional, Le Grand, Roger, additional, King, Megan, additional, Pawlotsky, Jean-Michel, additional, Manel, Nicolas, additional, Hofmann, Henning, additional, Vanwalscappel, Benedicte, additional, Bloch, Nicolin, additional, Landau, Nathaniel, additional, Indik, Stanislav, additional, Hagen, Benedikt, additional, Valle-Casuso, José Carlos, additional, Allouch, Awatef, additional, David, Annie, additional, Barré-Sinoussi, Françoise, additional, Benkirane, Monsef, additional, Pancino, Gianfranco, additional, Saez-Cirion, Asier, additional, Lee, Wing-Yiu, additional, Sloan, Richard, additional, Schulte, Bianca, additional, Blomberg, Jonas, additional, Vargiu, Luana, additional, Rodriguez-Tomé, Patricia, additional, Tramontano, Enzo, additional, Sperber, Göran, additional, Kumari, Namita, additional, Ammosova, Tatiana, additional, Diaz, Sharmeen, additional, Oneal, Patricia, additional, Nekhai, Sergei, additional, Fahrny, Audrey, additional, Gers-Huber, Gustavo, additional, Audigé, Annette, additional, Jayaprakash, Anitha, additional, Sachidanandam, Ravi, additional, Hernandez, Matt, additional, Dillon-White, Marsha, additional, Maze, Emmanuel, additional, Ham, Claire, additional, Almond, Neil, additional, Towers, Greg, additional, Belshaw, Robert, additional, de Sousa-Pereira, Patrícia, additional, Abrantes, Joana, additional, Pizzato, Massimo, additional, Esteves, Pedro J., additional, Kahle, Tanja, additional, Schmitt, Sven, additional, Merkel, Laura, additional, Reuter, Nina, additional, Stamminger, Thomas, additional, Rosa, Ilaria Dalla, additional, Bishop, Kate, additional, Spinazzola, Antonella, additional, Groom, Harriet, additional, Vieyres, Gabrielle, additional, Müsken, Mathias, additional, Zillinger, Thomas, additional, Hornung, Veit, additional, Barchet, Winfried, additional, Häussler, Susanne, additional, Pietschmann, Thomas, additional, Javed, Aneela, additional, Leuchte, Nicole, additional, Salinas, Gabriela, additional, Opitz, Lennart, additional, Sopper, Sieghart, additional, Mummert, Christiane, additional, Hofmann, Christian, additional, Hückelhoven, Angela G., additional, Bergmann, Silke, additional, Müller-Schmucker, Sandra M., additional, Harrer, Ellen G., additional, Dörrie, Jan, additional, Schaft, Niels, additional, Harrer, Thomas, additional, Cardinaux, Laure, additional, Zahno, M.- L., additional, Vogt, H.- R., additional, Zanoni, R., additional, Bertoni, G., additional, Muenchhoff, Maximilian, additional, Goulder, Philip, additional, Keppler, Oliver, additional, Rebensburg, Stephanie, additional, Helfer, Markus, additional, Zhang, Yuwei, additional, Chen, Huicheng, additional, Bernier, Annie, additional, Gosselin, Annie, additional, Routy, Jean- Pierre, additional, Wöhrl, Birgitta, additional, Schneider, Anna, additional, Corona, Angela, additional, Spöring, Imke, additional, Jordan, Mareike, additional, Buchholz, Bernd, additional, Maccioni, Elias, additional, Di Santo, Roberto, additional, Schweimer, Kristian, additional, Schölz, Christian, additional, Weinert, Brian, additional, Wagner, Sebastian, additional, Beli, Petra, additional, Miyake, Yasuyuki, additional, Qi, Jun, additional, Jensen, Lars, additional, Streicher, Werner, additional, McCarthy, Anna, additional, Westwood, Nicholas, additional, Lain, Sonia, additional, Cox, Jürgen, additional, Matthias, Patrick, additional, Mann, Matthias, additional, Bradner, James, additional, Choudhary, Chunaram, additional, Stern, Marcel, additional, Valletta, Elena, additional, Frezza, Caterina, additional, Marino-Merlo, Francesca, additional, Grelli, Sandro, additional, Serafino, Anna Lucia, additional, Mastino, Antonio, additional, Macchi, Beatrice, additional, Kaulfuß, Meike, additional, Windmann, Sonja, additional, Bayer, Wibke, additional, Mikasi, Sello, additional, Heß, Rebecca, additional, Bonsmann, Michael Storcksdieck gen., additional, Kirschning, Carsten, additional, Lepenies, Bernd, additional, Kolenbrander, Anne, additional, Temchura, Vladimir, additional, Iijima, Kenta, additional, Kobayashi, Junya, additional, and Ishizaka, Yukihito, additional

Published
2016
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34. Vectores recombinantes basados en el virus modificado de Ankara (MVA) com vacunas preventivas y terapeúticas contra la hepatitis C

Author

Esteban, Mariano, Gómez, Carmen E., and Perdiguero, Beatriz

Subjects
viruses, virus diseases, biochemical phenomena, metabolism, and nutrition, digestive system diseases
Abstract

[EN] The recombinant viruses of the invention contain sequences which are inserted at the same site of insertion as that of MVA and allow the simultaneous expression of various antigens of the HCV, concretely the structural (Core, E1, E2 and p7) and non-structural (NS2, NS3, NS4A, NS4B, NS5A plus the 201 amino acids of the N-terminal region of NS5B) mature proteins. In this way, stable recombinant viruses are obtained, which allow an immune response to be triggered against a large variety of antigens of the HCV, suitable for being used as preventive and therapeutic vaccines against hepatitis C., [ES] Los virus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y que permiten la expresión simultáneamente de varios antígenos del VHC, concretamente las proteínas maduras estructurales (Core, E1, E2 y p7) y no estructurales (NS2, NS3, NS4A, NS4B, NS5A más los 201 aminoácidos de la región N-terminal de NS5B). Con ello se consiguen virus recombinantes estables, que permiten el desencadenamiento de una respuesta inmune contra una gran variedad de antígenos del VHC, adecuados para ser utilizados como vacunas preventivas y terapéuticas contra la hepatitis C., Consejo Superior de investigaciones Científicas, A1 Solicitud de patente con informe sobre el estado de la técnica

Published
2014

35. Recombinant vectors based on the modified vaccinia Ankara virus (MVA) as preventive and therapeutic vaccines against hepatitis C

Author

Esteban, Mariano, Gómez, Carmen E., and Perdiguero, Beatriz

Abstract

[EN] The recombinant viruses of the invention contain sequences which are inserted at the same site of insertion as that of MVA and allow the simultaneous expression of various antigens of the HCV, concretely the structural (Core, E1, E2 and p7) and non-structural (NS2, NS3, NS4A, NS4B, NS5A plus the 201 amino acids of the N-terminal region of NS5B) mature proteins. In this way, stable recombinant viruses are obtained, which allow an immune response to be triggered against a large variety of antigens of the HCV, suitable for being used as preventive and therapeutic vaccines against hepatitis C. [ES] Los virus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y que permiten la expresión simultáneamente de varios antígenos del VHC, concretamente las proteínas maduras estructurales (Core, E1, E2 y p7) y no estructurales (NS2, NS3, NS4A, NS4B, NS5A más los 201 aminoácidos de la región N-terminal de NS5B). Con ello se consiguen virus recombinantes estables, que permiten el desencadenamiento de una respuesta inmune contra una gran variedad de antígenos del VHC, adecuados para ser utilizados como vacunas preventivas y terapéuticas contra la hepatitis C. Peer reviewed Consejo Superior de investigaciones Científicas A1 Solicitud de patente con informe sobre el estado de la técnica

Published
2014

36. A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART

Author

Gómez, Carmen Elena, primary, Perdiguero, Beatriz, additional, García-Arriaza, Juan, additional, Cepeda, Victoria, additional, Sánchez-Sorzano, Carlos Óscar, additional, Mothe, Beatriz, additional, Jiménez, José Luis, additional, Muñoz-Fernández, María Ángeles, additional, Gatell, Jose M., additional, López Bernaldo de Quirós, Juan Carlos, additional, Brander, Christian, additional, García, Felipe, additional, and Esteban, Mariano, additional

Published
2015
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37. Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates

Author

García-Arriaza, Juan, primary, Perdiguero, Beatriz, additional, Heeney, Jonathan, additional, Seaman, Michael, additional, Montefiori, David C., additional, Labranche, Celia, additional, Yates, Nicole L., additional, Shen, Xiaoying, additional, Tomaras, Georgia D., additional, Ferrari, Guido, additional, Foulds, Kathryn E., additional, McDermott, Adrian, additional, Kao, Shing-Fen, additional, Roederer, Mario, additional, Hawkins, Natalie, additional, Self, Steve, additional, Yao, Jiansheng, additional, Farrell, Patrick, additional, Phogat, Sanjay, additional, Tartaglia, Jim, additional, Barnett, Susan W., additional, Burke, Brian, additional, Cristillo, Anthony, additional, Weiss, Deborah, additional, Lee, Carter, additional, Kibler, Karen, additional, Jacobs, Bert, additional, Asbach, Benedikt, additional, Wagner, Ralf, additional, Ding, Song, additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2015
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38. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways.

Author

Gómez, Carmen Elena, Perdiguero, Beatriz, Sánchez-Corzo, Cristina, Sorzano, Carlos Oscar S., and Esteban, Mariano

Subjects
*HIV infections, *THERAPEUTICS, *AIDS vaccines, *VIRAL genes, *DELETION mutation, *IMMUNOREGULATION, *VIRUSES
Abstract

An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC) poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors--TLR--interferon, cytokines/chemokines), as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell) to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV) genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases. [ABSTRACT FROM AUTHOR]

Published
2018
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39. Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization.

Author

C. Guardo, Alberto, Gómez, Carmen Elena, Díaz-Brito, Vicens, Pich, Judit, Arnaiz, Joan Albert, Perdiguero, Beatriz, García-Arriaza, Juan, González, Nuria, Sorzano, Carlos O. S., Jiménez, Laura, Jiménez, José Luis, Muñoz-Fernández, María Ángeles, Gatell, José M, Alcamí, José, Esteban, Mariano, López Bernaldo de Quirós, Juan Carlos, García, Felipe, Plana, Montserrat, and null, null

Subjects
VACCINES, AIDS vaccines, IMMUNE response, HUMORAL immunity, IMMUNIZATION, ANTIBODY formation, T cells
Abstract

Background: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. Methods: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. Results: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. Conclusions: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Published
2017
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40. Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C

Author

Gómez, Carmen Elena, Perdiguero, Beatriz, Jiménez, Victoria, Filali-Mouhim, Abdelali, Ghneim, Khader, Haddad, Elias K., Quakkerlaar, Esther D., Delaloye, Julie, Harari, Alexandre, Roger, Thierry, Duhen, Thomas, Sékaly, Rafick P., Melief, Cornelis J. M., Calandra, Thierry, Sallusto, Federica, Lanzavecchia, Antonio, Wagner, Ralf, Pantaleo, Giuseppe, and Esteban, Mariano

Subjects
Multidisciplinary, Science, lcsh:R, Medicine, lcsh:Medicine, Correction, lcsh:Q, lcsh:Science
Published
2012

41. Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost

Author

Hulot, Sandrine L., primary, Korber, Bette, additional, Giorgi, Elena E., additional, Vandergrift, Nathan, additional, Saunders, Kevin O., additional, Balachandran, Harikrishnan, additional, Mach, Linh V., additional, Lifton, Michelle A., additional, Pantaleo, Giuseppe, additional, Tartaglia, Jim, additional, Phogat, Sanjay, additional, Jacobs, Bertram, additional, Kibler, Karen, additional, Perdiguero, Beatriz, additional, Gomez, Carmen E., additional, Esteban, Mariano, additional, Rosati, Margherita, additional, Felber, Barbara K., additional, Pavlakis, George N., additional, Parks, Robert, additional, Lloyd, Krissey, additional, Sutherland, Laura, additional, Scearce, Richard, additional, Letvin, Norman L., additional, Seaman, Michael S., additional, Alam, S. Munir, additional, Montefiori, David, additional, Liao, Hua-Xin, additional, Haynes, Barton F., additional, and Santra, Sampa, additional

Published
2015
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42. The Evolution of Poxvirus Vaccines

Author

Sánchez-Sampedro, Lucas, primary, Perdiguero, Beatriz, additional, Mejías-Pérez, Ernesto, additional, García-Arriaza, Juan, additional, Di Pilato, Mauro, additional, and Esteban, Mariano, additional

Published
2015
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43. Interleukin-1- and Type I Interferon-Dependent Enhanced Immunogenicity of an NYVAC-HIV-1 Env-Gag-Pol-Nef Vaccine Vector with Dual Deletions of Type I and Type II Interferon-Binding Proteins

Author

Delaloye, Julie, primary, Filali-Mouhim, Abdelali, additional, Cameron, Mark J., additional, Haddad, Elias K., additional, Harari, Alexandre, additional, Goulet, Jean-Pierre, additional, Gomez, Carmen E., additional, Perdiguero, Beatriz, additional, Esteban, Mariano, additional, Pantaleo, Giuseppe, additional, Roger, Thierry, additional, Sékaly, Rafick-Pierre, additional, and Calandra, Thierry, additional

Published
2015
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44. Virological and Immunological Characterization of Novel NYVAC-Based HIV/AIDS Vaccine Candidates Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as Virus-Like Particles

Author

Perdiguero, Beatriz, primary, Gómez, Carmen Elena, additional, Cepeda, Victoria, additional, Sánchez-Sampedro, Lucas, additional, García-Arriaza, Juan, additional, Mejías-Pérez, Ernesto, additional, Jiménez, Victoria, additional, Sánchez, Cristina, additional, Sorzano, Carlos Óscar S., additional, Oliveros, Juan Carlos, additional, Delaloye, Julie, additional, Roger, Thierry, additional, Calandra, Thierry, additional, Asbach, Benedikt, additional, Wagner, Ralf, additional, Kibler, Karen V., additional, Jacobs, Bertram L., additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2015
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45. Bivalent NYVAC-based Vaccine Candidates against HIV/AIDS Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as VLPs

Author

Perdiguero, Beatriz, primary, Gómez, Carmen Elena, additional, Cepeda, María Victoria, additional, Sánchez-Sampedro, Lucas, additional, García-Arriaza, Juan, additional, Mejías-Pérez, Ernesto, additional, Jiménez, Victoria, additional, Sánchez, Cristina, additional, Sorzano, Carlos Oscar S., additional, Delaloye, Julie, additional, Roger, Thierry, additional, Calandra, Thierry, additional, Wagner, Ralf, additional, Asbach, Benedikt, additional, Kibler, Karen V., additional, Jacobs, Bertram L, additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2014
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46. Vaccinia Virus with Selective Deletions Enhances T Cell Response to HIV Antigens by Specific Neutrophil Recruitment

Author

Di Pilato, Mauro, primary, Mejías-Pérez, Ernesto, additional, Zonca, Manuela, additional, Perdiguero, Beatriz, additional, Gómez, Carmen Elena, additional, Trakala, Marianna, additional, Nieto, Jacobo, additional, Nájera, José Luis, additional, Sorzano, Carlos Oscar S., additional, Planelles, Lourdes, additional, and Esteban, Mariano, additional

Published
2014
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49. Deletion of the Vaccinia Virus Gene A46R, Encoding for an Inhibitor of TLR Signalling, Is an Effective Approach to Enhance the Immunogenicity in Mice of the HIV/AIDS Vaccine Candidate NYVAC-C

Author

Perdiguero, Beatriz, primary, Gómez, Carmen Elena, additional, Di Pilato, Mauro, additional, Sorzano, Carlos Oscar S., additional, Delaloye, Julie, additional, Roger, Thierry, additional, Calandra, Thierry, additional, Pantaleo, Giuseppe, additional, and Esteban, Mariano, additional

Published
2013
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50. High, Broad, Polyfunctional, and Durable T Cell Immune Responses Induced in Mice by a Novel Hepatitis C Virus (HCV) Vaccine Candidate (MVA-HCV) Based on Modified Vaccinia Virus Ankara Expressing the Nearly Full-Length HCV Genome

Author

Gómez, Carmen E., primary, Perdiguero, Beatriz, additional, Cepeda, María Victoria, additional, Mingorance, Lidia, additional, García-Arriaza, Juan, additional, Vandermeeren, Andrea, additional, Sorzano, Carlos Óscar S., additional, and Esteban, Mariano, additional

Published
2013
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