Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.

<h4>Unlabelled</h4>The objectives of this non-randomized, non-blinded, dose-escalating Phase I clinical trial were to assess the safety, reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel (aluminum hydroxide) in 51 healthy, malaria-naive adults aged 18 to 45 years....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Aric L Gregson, Giane Oliveira, Caroline Othoro, J Mauricio Calvo-Calle, George B Thorton, Elizabeth Nardin, Robert Edelman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/571b5bbd1ab04ea8a90603cae73cfdf8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:571b5bbd1ab04ea8a90603cae73cfdf8
record_format	dspace
spelling	oai:doaj.org-article:571b5bbd1ab04ea8a90603cae73cfdf82021-11-25T06:13:28ZPhase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.1932-620310.1371/journal.pone.0001556https://doaj.org/article/571b5bbd1ab04ea8a90603cae73cfdf82008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18253503/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>The objectives of this non-randomized, non-blinded, dose-escalating Phase I clinical trial were to assess the safety, reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel (aluminum hydroxide) in 51 healthy, malaria-naive adults aged 18 to 45 years. ICC-1132 (Malariavax) is a recombinant, virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [(NANP)(3)] epitope, an HLA-restricted CD4 (NANPNVDPNANP) epitope and a universal T cell epitope (T*) (amino acids 326-345, NF54 isolate). We assessed an Alhydrogel (aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels, each injected intramuscularly (1.0 mL) on study days 0, 56 and 168. A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study. Thirty-two volunteers were followed for one year. Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays: IgG and IgM ELISA, indirect immunofluorescence against P. falciparum sporozoites, circumsporozoite precipitin (CSP) and transgenic sporozoite neutralization assays. Cellular responses were measured by proliferation and IL-2 assays. Local and systemic reactions were similarly mild and well tolerated between dose cohorts. Depending on the ICC-1132 vaccine concentration, 95 to 100% of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections; however, only 29-75% and 29-63% of volunteers, respectively, developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA; 2 of 8 volunteers had positive reactions in the CSP assay. Maximal transgenic sporozoite neutralization assay inhibition was 54%. Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein (rCS) NF-54 isolate. This candidate malaria vaccine was well tolerated, but the vaccine formulation was poorly immunogenic. The vaccine may benefit from a more powerful adjuvant to improve immunogenicity.<h4>Trial registration</h4>ClinicalTrials.gov NCT00587249.Aric L GregsonGiane OliveiraCaroline OthoroJ Mauricio Calvo-CalleGeorge B ThortonElizabeth NardinRobert EdelmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 2, p e1556 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aric L Gregson Giane Oliveira Caroline Othoro J Mauricio Calvo-Calle George B Thorton Elizabeth Nardin Robert Edelman Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
description	<h4>Unlabelled</h4>The objectives of this non-randomized, non-blinded, dose-escalating Phase I clinical trial were to assess the safety, reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel (aluminum hydroxide) in 51 healthy, malaria-naive adults aged 18 to 45 years. ICC-1132 (Malariavax) is a recombinant, virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [(NANP)(3)] epitope, an HLA-restricted CD4 (NANPNVDPNANP) epitope and a universal T cell epitope (T*) (amino acids 326-345, NF54 isolate). We assessed an Alhydrogel (aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels, each injected intramuscularly (1.0 mL) on study days 0, 56 and 168. A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study. Thirty-two volunteers were followed for one year. Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays: IgG and IgM ELISA, indirect immunofluorescence against P. falciparum sporozoites, circumsporozoite precipitin (CSP) and transgenic sporozoite neutralization assays. Cellular responses were measured by proliferation and IL-2 assays. Local and systemic reactions were similarly mild and well tolerated between dose cohorts. Depending on the ICC-1132 vaccine concentration, 95 to 100% of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections; however, only 29-75% and 29-63% of volunteers, respectively, developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA; 2 of 8 volunteers had positive reactions in the CSP assay. Maximal transgenic sporozoite neutralization assay inhibition was 54%. Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein (rCS) NF-54 isolate. This candidate malaria vaccine was well tolerated, but the vaccine formulation was poorly immunogenic. The vaccine may benefit from a more powerful adjuvant to improve immunogenicity.<h4>Trial registration</h4>ClinicalTrials.gov NCT00587249.
format	article
author	Aric L Gregson Giane Oliveira Caroline Othoro J Mauricio Calvo-Calle George B Thorton Elizabeth Nardin Robert Edelman
author_facet	Aric L Gregson Giane Oliveira Caroline Othoro J Mauricio Calvo-Calle George B Thorton Elizabeth Nardin Robert Edelman
author_sort	Aric L Gregson
title	Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
title_short	Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
title_full	Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
title_fullStr	Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
title_full_unstemmed	Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
title_sort	phase i trial of an alhydrogel adjuvanted hepatitis b core virus-like particle containing epitopes of plasmodium falciparum circumsporozoite protein.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/571b5bbd1ab04ea8a90603cae73cfdf8
work_keys_str_mv	AT ariclgregson phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT gianeoliveira phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT carolineothoro phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT jmauriciocalvocalle phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT georgebthorton phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT elizabethnardin phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein AT robertedelman phaseitrialofanalhydrogeladjuvantedhepatitisbcoreviruslikeparticlecontainingepitopesofplasmodiumfalciparumcircumsporozoiteprotein
_version_	1718413983416844288

Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.

Ejemplares similares