Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization
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 voluntee...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/6880 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/6880 |
| Access Level: | acceso abierto |
| Palabra clave: | AIDS Vaccines Antibodies, Neutralizing CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enzyme-Linked Immunosorbent Assay Flow Cytometry HIV Antibodies HIV-1 Healthy Volunteers Humans Placebos Immunization, Secondary |
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Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunizationGuardo, Alberto CGómez, Carmen ElenaDíaz-Brito, VicensPich, JuditArnaiz, Joan AlbertPerdiguero, BeatrizGarcía-Arriaza, JuanGonzalez-Fernandez, NuriaSorzano, Carlos O SJiménez, LauraJiménez, José LuisMuñoz-Fernández, María ÁngelesGatell, José MAlcamí, JoséEsteban, MarianoLópez Bernaldo de Quirós, Juan CarlosGarcía, FelipePlana, MontserratAIDS VaccinesAntibodies, NeutralizingCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFlow CytometryHIV AntibodiesHIV-1Healthy VolunteersHumansPlacebosImmunization, SecondaryBACKGROUND: 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.Public Library of Science (PLOS)Instituto de Salud Carlos IIIInstitut d’Investigacions Biomédiques August Pi I Sunyer20182018-12-1720172017-10-2420172017-10-24journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6880reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES PI12 00969ES PI15 00480ES SAF2015-66193-R Not availableES SAF2013-45232-R Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/68802026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| title |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| spellingShingle |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization Guardo, Alberto C AIDS Vaccines Antibodies, Neutralizing CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enzyme-Linked Immunosorbent Assay Flow Cytometry HIV Antibodies HIV-1 Healthy Volunteers Humans Placebos Immunization, Secondary |
| title_short |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| title_full |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| title_fullStr |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| title_full_unstemmed |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| title_sort |
Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization |
| dc.creator.none.fl_str_mv |
Guardo, Alberto C Gómez, Carmen Elena Díaz-Brito, Vicens Pich, Judit Arnaiz, Joan Albert Perdiguero, Beatriz García-Arriaza, Juan Gonzalez-Fernandez, 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 |
| author |
Guardo, Alberto C |
| author_facet |
Guardo, Alberto C Gómez, Carmen Elena Díaz-Brito, Vicens Pich, Judit Arnaiz, Joan Albert Perdiguero, Beatriz García-Arriaza, Juan Gonzalez-Fernandez, 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 |
| author_role |
author |
| author2 |
Gómez, Carmen Elena Díaz-Brito, Vicens Pich, Judit Arnaiz, Joan Albert Perdiguero, Beatriz García-Arriaza, Juan Gonzalez-Fernandez, 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 |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III Institut d’Investigacions Biomédiques August Pi I Sunyer |
| dc.subject.none.fl_str_mv |
AIDS Vaccines Antibodies, Neutralizing CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enzyme-Linked Immunosorbent Assay Flow Cytometry HIV Antibodies HIV-1 Healthy Volunteers Humans Placebos Immunization, Secondary |
| topic |
AIDS Vaccines Antibodies, Neutralizing CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enzyme-Linked Immunosorbent Assay Flow Cytometry HIV Antibodies HIV-1 Healthy Volunteers Humans Placebos Immunization, Secondary |
| description |
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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2017-10-24 2017 2017-10-24 2018 2018-12-17 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/6880 |
| url |
http://hdl.handle.net/20.500.12105/6880 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
ES PI12 00969 ES PI15 00480 ES SAF2015-66193-R Not available ES SAF2013-45232-R Not available |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Public Library of Science (PLOS) |
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Public Library of Science (PLOS) |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
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Instituto de Salud Carlos III (ISCIII) |
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Repisalud |
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Repisalud |
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1869403720636170240 |
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15.81155 |