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Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines

Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited...

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Autores principales: Titti, Fausto, Maggiorella, Maria T., Ferrantelli, Flavia, Sernicola, Leonardo, Bellino, Stefania, Collacchi, Barbara, Belasio, Emanuele Fanales, Moretti, Sonia, Pavone Cossut, Maria Rosaria, Belli, Roberto, Olivieri, Erika, Farcomeni, Stefania, Compagnoni, Daniela, Michelini, Zuleika, Sabbatucci, Michela, Sparnacci, Katia, Tondelli, Luisa, Laus, Michele, Cafaro, Aurelio, Caputo, Antonella, Ensoli, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214729/
https://www.ncbi.nlm.nih.gov/pubmed/25356594
http://dx.doi.org/10.1371/journal.pone.0111360
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author Titti, Fausto
Maggiorella, Maria T.
Ferrantelli, Flavia
Sernicola, Leonardo
Bellino, Stefania
Collacchi, Barbara
Belasio, Emanuele Fanales
Moretti, Sonia
Pavone Cossut, Maria Rosaria
Belli, Roberto
Olivieri, Erika
Farcomeni, Stefania
Compagnoni, Daniela
Michelini, Zuleika
Sabbatucci, Michela
Sparnacci, Katia
Tondelli, Luisa
Laus, Michele
Cafaro, Aurelio
Caputo, Antonella
Ensoli, Barbara
author_facet Titti, Fausto
Maggiorella, Maria T.
Ferrantelli, Flavia
Sernicola, Leonardo
Bellino, Stefania
Collacchi, Barbara
Belasio, Emanuele Fanales
Moretti, Sonia
Pavone Cossut, Maria Rosaria
Belli, Roberto
Olivieri, Erika
Farcomeni, Stefania
Compagnoni, Daniela
Michelini, Zuleika
Sabbatucci, Michela
Sparnacci, Katia
Tondelli, Luisa
Laus, Michele
Cafaro, Aurelio
Caputo, Antonella
Ensoli, Barbara
author_sort Titti, Fausto
collection PubMed
description Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6P(cy243), vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4(+) T cell depletion rate during the acute phase of infection and higher ability to resume the CD4(+) T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.
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spelling pubmed-42147292014-11-05 Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines Titti, Fausto Maggiorella, Maria T. Ferrantelli, Flavia Sernicola, Leonardo Bellino, Stefania Collacchi, Barbara Belasio, Emanuele Fanales Moretti, Sonia Pavone Cossut, Maria Rosaria Belli, Roberto Olivieri, Erika Farcomeni, Stefania Compagnoni, Daniela Michelini, Zuleika Sabbatucci, Michela Sparnacci, Katia Tondelli, Luisa Laus, Michele Cafaro, Aurelio Caputo, Antonella Ensoli, Barbara PLoS One Research Article Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6P(cy243), vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4(+) T cell depletion rate during the acute phase of infection and higher ability to resume the CD4(+) T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates. Public Library of Science 2014-10-30 /pmc/articles/PMC4214729/ /pubmed/25356594 http://dx.doi.org/10.1371/journal.pone.0111360 Text en © 2014 Titti et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Titti, Fausto
Maggiorella, Maria T.
Ferrantelli, Flavia
Sernicola, Leonardo
Bellino, Stefania
Collacchi, Barbara
Belasio, Emanuele Fanales
Moretti, Sonia
Pavone Cossut, Maria Rosaria
Belli, Roberto
Olivieri, Erika
Farcomeni, Stefania
Compagnoni, Daniela
Michelini, Zuleika
Sabbatucci, Michela
Sparnacci, Katia
Tondelli, Luisa
Laus, Michele
Cafaro, Aurelio
Caputo, Antonella
Ensoli, Barbara
Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title_full Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title_fullStr Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title_full_unstemmed Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title_short Biocompatible Anionic Polymeric Microspheres as Priming Delivery System for Effetive HIV/AIDS Tat-Based Vaccines
title_sort biocompatible anionic polymeric microspheres as priming delivery system for effetive hiv/aids tat-based vaccines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214729/
https://www.ncbi.nlm.nih.gov/pubmed/25356594
http://dx.doi.org/10.1371/journal.pone.0111360
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