Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infec...

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Autores: Álvarez Fernández, Carmen, Crespo Guardo, Alberto, García-Pérez, Javier, García Alcaide, Felipe, Blanco, Julià, Escribà-García, Laura, Gatell, José M., Alcamí, José, Plana Prades, Montserrat, Sánchez-Palomino, Sonsoles
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/124798
Acceso en línea:https://hdl.handle.net/2445/124798
Access Level:acceso abierto
Palabra clave:VIH (Virus)
Vacunes
Immunologia
HIV (Viruses)
Vaccines
Immunology
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spelling Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccineÁlvarez Fernández, CarmenCrespo Guardo, AlbertoGarcía-Pérez, JavierGarcía Alcaide, FelipeBlanco, JuliàEscribà-García, LauraGatell, José M.Alcamí, JoséPlana Prades, MontserratSánchez-Palomino, SonsolesVIH (Virus)VacunesImmunologiaHIV (Viruses)VaccinesImmunologyBackground The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.Public Library of Science (PLoS)2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/124798Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0048848PLoS One, 2012, vol. 7, num. 11, p. e48848https://doi.org/10.1371/journal.pone.0048848cc-by (c) Álvarez Fernández, Carmen et al., 2012http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1247982026-05-27T06:46:51Z
dc.title.none.fl_str_mv Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
title Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
spellingShingle Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
Álvarez Fernández, Carmen
VIH (Virus)
Vacunes
Immunologia
HIV (Viruses)
Vaccines
Immunology
title_short Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
title_full Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
title_fullStr Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
title_full_unstemmed Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
title_sort Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
dc.creator.none.fl_str_mv Álvarez Fernández, Carmen
Crespo Guardo, Alberto
García-Pérez, Javier
García Alcaide, Felipe
Blanco, Julià
Escribà-García, Laura
Gatell, José M.
Alcamí, José
Plana Prades, Montserrat
Sánchez-Palomino, Sonsoles
author Álvarez Fernández, Carmen
author_facet Álvarez Fernández, Carmen
Crespo Guardo, Alberto
García-Pérez, Javier
García Alcaide, Felipe
Blanco, Julià
Escribà-García, Laura
Gatell, José M.
Alcamí, José
Plana Prades, Montserrat
Sánchez-Palomino, Sonsoles
author_role author
author2 Crespo Guardo, Alberto
García-Pérez, Javier
García Alcaide, Felipe
Blanco, Julià
Escribà-García, Laura
Gatell, José M.
Alcamí, José
Plana Prades, Montserrat
Sánchez-Palomino, Sonsoles
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv VIH (Virus)
Vacunes
Immunologia
HIV (Viruses)
Vaccines
Immunology
topic VIH (Virus)
Vacunes
Immunologia
HIV (Viruses)
Vaccines
Immunology
description Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/124798
url https://hdl.handle.net/2445/124798
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0048848
PLoS One, 2012, vol. 7, num. 11, p. e48848
https://doi.org/10.1371/journal.pone.0048848
dc.rights.none.fl_str_mv cc-by (c) Álvarez Fernández, Carmen et al., 2012
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Álvarez Fernández, Carmen et al., 2012
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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