International network for comparison of HIV neutralization assays: the NeutNet report II

BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, bu...

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Autores: Heyndrickx, Leo, Heath, Alan, Sheik-Khalil, Enas, Alcamí, José, Bongertz, Vera, Jansson, Marianne, Malnati, Mauro, Montefiori, David, Moog, Christiane, Morris, Lynn, Osmanov, Saladin, Polonis, Victoria, Ramaswamy, Meghna, Sattentau, Quentin, Tolazzi, Monica, Schuitemaker, Hanneke, Willems, Betty, Wrin, Terri, Fenyö, Eva Maria, Scarlatti, Gabriella
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6808
Acceso en línea:http://hdl.handle.net/20.500.12105/6808
Access Level:acceso abierto
Palabra clave:AIDS Vaccines
Antibodies, Neutralizing
Biological Assay
Female
HIV Antibodies
HIV Infections
HeLa Cells
Humans
Male
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spelling International network for comparison of HIV neutralization assays: the NeutNet report IIHeyndrickx, LeoHeath, AlanSheik-Khalil, EnasAlcamí, JoséBongertz, VeraJansson, MarianneMalnati, MauroMontefiori, DavidMoog, ChristianeMorris, LynnOsmanov, SaladinPolonis, VictoriaRamaswamy, MeghnaSattentau, QuentinTolazzi, MonicaSchuitemaker, HannekeWillems, BettyWrin, TerriFenyö, Eva MariaScarlatti, GabriellaAIDS VaccinesAntibodies, NeutralizingBiological AssayFemaleHIV AntibodiesHIV InfectionsHeLa CellsHumansMaleBACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation.Public Library of Science (PLOS)Fund for Scientific Research (Belgica)Unión Europea. Comisión EuropeaWorld Health Organization (WHO/OMS)Instituto de Salud Carlos IIIEuropriseFundación para la Innovación y la Prospectiva en Salud en EspañaIstituto Superiore di Sanità (Italia)Swedish Research CouncilSwedish International Development Cooperation AgencyBill & Melinda Gates Foundation20182018-12-1120122012-05-0920122012-05-09research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6808reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 201433open 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:20.500.12105/68082026-06-12T12:43:37Z
dc.title.none.fl_str_mv International network for comparison of HIV neutralization assays: the NeutNet report II
title International network for comparison of HIV neutralization assays: the NeutNet report II
spellingShingle International network for comparison of HIV neutralization assays: the NeutNet report II
Heyndrickx, Leo
AIDS Vaccines
Antibodies, Neutralizing
Biological Assay
Female
HIV Antibodies
HIV Infections
HeLa Cells
Humans
Male
title_short International network for comparison of HIV neutralization assays: the NeutNet report II
title_full International network for comparison of HIV neutralization assays: the NeutNet report II
title_fullStr International network for comparison of HIV neutralization assays: the NeutNet report II
title_full_unstemmed International network for comparison of HIV neutralization assays: the NeutNet report II
title_sort International network for comparison of HIV neutralization assays: the NeutNet report II
dc.creator.none.fl_str_mv Heyndrickx, Leo
Heath, Alan
Sheik-Khalil, Enas
Alcamí, José
Bongertz, Vera
Jansson, Marianne
Malnati, Mauro
Montefiori, David
Moog, Christiane
Morris, Lynn
Osmanov, Saladin
Polonis, Victoria
Ramaswamy, Meghna
Sattentau, Quentin
Tolazzi, Monica
Schuitemaker, Hanneke
Willems, Betty
Wrin, Terri
Fenyö, Eva Maria
Scarlatti, Gabriella
author Heyndrickx, Leo
author_facet Heyndrickx, Leo
Heath, Alan
Sheik-Khalil, Enas
Alcamí, José
Bongertz, Vera
Jansson, Marianne
Malnati, Mauro
Montefiori, David
Moog, Christiane
Morris, Lynn
Osmanov, Saladin
Polonis, Victoria
Ramaswamy, Meghna
Sattentau, Quentin
Tolazzi, Monica
Schuitemaker, Hanneke
Willems, Betty
Wrin, Terri
Fenyö, Eva Maria
Scarlatti, Gabriella
author_role author
author2 Heath, Alan
Sheik-Khalil, Enas
Alcamí, José
Bongertz, Vera
Jansson, Marianne
Malnati, Mauro
Montefiori, David
Moog, Christiane
Morris, Lynn
Osmanov, Saladin
Polonis, Victoria
Ramaswamy, Meghna
Sattentau, Quentin
Tolazzi, Monica
Schuitemaker, Hanneke
Willems, Betty
Wrin, Terri
Fenyö, Eva Maria
Scarlatti, Gabriella
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fund for Scientific Research (Belgica)
Unión Europea. Comisión Europea
World Health Organization (WHO/OMS)
Instituto de Salud Carlos III
Europrise
Fundación para la Innovación y la Prospectiva en Salud en España
Istituto Superiore di Sanità (Italia)
Swedish Research Council
Swedish International Development Cooperation Agency
Bill & Melinda Gates Foundation
dc.subject.none.fl_str_mv AIDS Vaccines
Antibodies, Neutralizing
Biological Assay
Female
HIV Antibodies
HIV Infections
HeLa Cells
Humans
Male
topic AIDS Vaccines
Antibodies, Neutralizing
Biological Assay
Female
HIV Antibodies
HIV Infections
HeLa Cells
Humans
Male
description BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-05-09
2012
2012-05-09
2018
2018-12-11
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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/20.500.12105/6808
url http://hdl.handle.net/20.500.12105/6808
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 201433
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
rights_invalid_str_mv 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)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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