Publication:
International network for comparison of HIV neutralization assays: The NeutNet report

Issued Date

2009-02-20

Resource Type

Article

ISSN

19326203

DOI

10.1371/journal.pone.0004505

Other identifier(s)

2-s2.0-84887212581

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS ONE. Vol.4, No.2 (2009)

Suggested Citation

Eva Maria Fenyö, Alan Heath, Stefania Dispinseri, Harvey Holmes, Paolo Lusso, Susan Zolla-Pazner, Helen Donners, Leo Heyndrickx, Jose Alcami, Vera Bongertz, Christian Jassoy, Mauro Malnati, David Montefiori, Christiane Moog, Lynn Morris, Saladin Osmanov, Victoria Polonis, Quentin Sattentau, Hanneke Schuitemaker, Ruengpung Sutthent, Terri Wrin, Gabriella Scarlatti International network for comparison of HIV neutralization assays: The NeutNet report. PLoS ONE. Vol.4, No.2 (2009). doi:10.1371/journal.pone.0004505 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/27053

Research Projects

Organizational Units

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Title

International network for comparison of HIV neutralization assays: The NeutNet report

Author(s)

Eva Maria Fenyö
 Alan Heath
 Stefania Dispinseri
 Harvey Holmes
 Paolo Lusso
 Susan Zolla-Pazner
 Helen Donners
 Leo Heyndrickx
 Jose Alcami
 Vera Bongertz
 Christian Jassoy
 Mauro Malnati
 David Montefiori
 Christiane Moog
 Lynn Morris
 Saladin Osmanov
 Victoria Polonis
 Quentin Sattentau
 Hanneke Schuitemaker
 Ruengpung Sutthent
 Terri Wrin
 Gabriella Scarlatti

Other Contributor(s)

Instituto de Salud Carlos III
 Fundação Oswaldo
 IRCCS San Raffaele Scientific Institute
 Prins Leopold Instituut voor Tropische Geneeskunde
 Lunds Universitet
 National Institute for Biological Standards and Control
 Universitat Leipzig
 Duke University School of Medicine
 Universite de Strasbourg
 National Institute for Communicable Diseases
 Organisation Mondiale de la Sante
 HJF
 Sir William Dunn School of Pathology
 University of Amsterdam
 Mahidol University
 Monogram Biosciences
 NYU School of Medicine
 National Institute of Allergy and Infectious Diseases

Abstract

Background: Neutralizing antibody assessments play a central role in human immunodeficiency virus type-1 (HIV-1) vaccine development but it is unclear which assay, or combination of assays, will provide reliable measures of correlates of protection. To address this, an international collaboration (NeutNet) involving 18 independent participants was organized to compare different assays. Methods: Each laboratory evaluated four neutralizing reagents (TriMab, 447-52D, 4E10, sCD4) at a given range of concentrations against a panel of 11 viruses representing a wide range of genetic subtypes and phenotypes. A total of 16 different assays were compared. The assays utilized either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (virus infectivity assays, VI assays), or their Env-pseudotyped (gp160) derivatives produced in 293T cells (PSV assays) from molecular clones or uncloned virus. Target cells included PBMC and genetically-engineered cell lines in either a single-or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs that included extracellular or intracellular p24 antigen detection, RNA quantification and luciferase and beta-galactosidase reporter gene expression. Findings: PSV assays were generally more sensitive than VI assays, but there were important differences according to the virus and inhibitor used. For example, for TriMab, the mean IC50 was always lower in PSV than in VI assays. However, with 4E10 or sCD4 some viruses were neutralized with a lower IC50 in VI assays than in the PSV assays. Inter-laboratory concordance was slightly better for PSV than for VI assays with some viruses, but for other viruses agreement between laboratories was limited and depended on both the virus and the neutralizing reagent. Conclusions: The NeutNet project demonstrated clear differences in assay sensitivity that were dependent on both the neutralizing reagent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities. Since it is not known which in vitro assay correlates with in vivo protection, a range of neutralization assays is recommended for vaccine evaluation. © 2009 Fenyö et al.

Keyword(s)

Agricultural and Biological Sciences
 Biochemistry, Genetics and Molecular Biology
 Medicine

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URI

https://repository.li.mahidol.ac.th/handle/123456789/27053

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