Titre
Generation of a Recombinant Gag Virus-Like-Particle Panel for the Evaluation of p24 Antigen Detection by Diagnostic HIV Tests.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Vetter, B.N.
Auteure/Auteur
Orlowski, V.
Auteure/Auteur
Fransen, K.
Auteure/Auteur
Niederhauser, C.
Auteure/Auteur
Aubert, V.
Auteure/Auteur
Brandenberger, M.
Auteure/Auteur
Ciardo, D.
Auteure/Auteur
Dollenmaier, G.
Auteure/Auteur
Klimkait, T.
Auteure/Auteur
Regenass, S.
Auteure/Auteur
Schmid, P.
Auteure/Auteur
Schottstedt, V.
Auteure/Auteur
Suter-Riniker, F.
Auteure/Auteur
Yerly, S.
Auteure/Auteur
Shah, C.
Auteure/Auteur
Böni, J.
Auteure/Auteur
Schüpbach, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2014
Volume
9
Numéro
10
Première page
e111552
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
BACKGROUND: Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens.
METHODS: We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection.
RESULTS: Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection.
CONCLUSIONS: The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.
METHODS: We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection.
RESULTS: Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection.
CONCLUSIONS: The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.
PID Serval
serval:BIB_1781BD45F2A9
PMID
Open Access
Oui
Date de création
2014-11-09T14:56:16.903Z
Date de création dans IRIS
2025-05-20T17:40:46Z
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BIB_1781BD45F2A9.P001.pdf
Version du manuscrit
preprint
Taille
913.31 KB
Format
Adobe PDF
PID Serval
serval:BIB_1781BD45F2A9.P001
URN
urn:nbn:ch:serval-BIB_1781BD45F2A90
Somme de contrôle
(MD5):5dfe31ae96506a5f2a2d0bba785848b5